Chienomoto Investigator-Initiated
Trial Collaboration Directions

Population

12–36 months of age, with language or global developmental delay (indicated as delayed by the Gesell language domain or the S-S language development delay test), with hearing impairment and clear genetic/metabolic disease excluded; currently receiving or about to begin early intervention training. n=30–50

Primary endpoint

24-week change in Gesell Developmental Schedules language domain developmental quotient

Secondary endpoints

Adaptive, personal-social, fine and gross motor domains; CDI (Chinese Communicative Development Inventory) vocabulary; sleep; feeding; parenting stress (PSI-SF)

Safety endpoints (key)

Growth curves (height, weight, head circumference), feeding and bowel movements, adverse events

Design

Parallel-arm comparison against “early intervention training alone,” 24 weeks

Publication angle

Ages 1–3 are a critical window for language and neurodevelopment, yet very few adjunct interventions are available for this age group. Both developmental pediatrics and rehabilitation departments can lead the study, and since these children already attend regular checkups and training sessions, follow-up adherence is extremely high.

This direction is currently the only applicable age range for No. 1. Safety and growth monitoring in young children must be rigorous — the protocol should be jointly reviewed by the company's medical department and expert advisors.

Population

12–36 months of age, with a history of prematurity (<34 weeks), low birth weight, hypoxic-ischemic encephalopathy, or neonatal brain injury, with Gesell or Bayley scores indicating developmental delay or borderline status. n=40–60

Primary endpoint

Bayley-III or Gesell cognitive, language, and motor domain developmental quotients

Secondary endpoints

BISQ infant sleep questionnaire, CBCL 1.5–5 emotional/behavioral problems, feeding status, parenting stress

Safety endpoints (key)

Growth curves, adverse events

Design

Prospective cohort + parallel-arm comparison, 24 weeks; recommend retaining the cohort for follow-up to age 3

Publication angle

High-risk infant follow-up clinics already have a fixed follow-up schedule and assessment system, so the marginal cost of data collection is extremely low. Retaining the cohort until age 3 for outcome assessment would multiply its value.

Population

6–16 years of age, on standardized methylphenidate or atomoxetine treatment for ≥4 weeks with a stable dose, SNAP-IV still at moderate severity or above; or forced to reduce dose due to decreased appetite, insomnia, or emotional rebound. n=40–60

Primary endpoint

12-week change in SNAP-IV parent-rated total score

Secondary endpoints

BRIEF executive function, CSHQ sleep, changes in appetite and weight, change in original medication dose, CGI-I

Design

Open-label pre-post comparison, or non-randomized parallel comparison against “standard regimen alone,” 12 weeks

Publication angle

“Partial response” and the “dose-reduction dilemma” are among the most common yet least-studied real-world scenarios in domestic ADHD clinics.

Population

6–14 years of age with ADHD, CSHQ total score ≥41 (indicating sleep problems), stable treatment regimen. n=40–60

Primary endpoint

CSHQ total score and sleep-onset latency subscale

Secondary endpoints

Sleep diary (time to fall asleep, number of night wakings), next-day SNAP-IV attention subscale, parent-reported sleep quality

Design

Open-label pre-post comparison or randomized controlled trial, 8–12 weeks

Publication angle

ADHD-related sleep problems and stimulant use are mutually reinforcing and are a major driver of poor parental adherence; domestic data are scarce.

Population

ADHD children who routinely stop or reduce medication during school holidays. n=40–60

Primary endpoint

SNAP-IV scores and frequency of emotional outbursts during the holiday medication-free period

Secondary endpoints

Weight catch-up, sleep, frequency of parent-child conflict, smoothness of medication resumption after returning to school

Design

Randomized to “medication cessation + Chienomoto” vs. “medication cessation alone,” 8 weeks (covering the entire holiday)

Publication angle

Extremely high feasibility — the recruitment window is concentrated, the follow-up period is naturally self-contained, and parental motivation is very strong; moreover, “medication holiday management” is almost entirely unstudied domestically.

Population

8–16 years of age, with ADHD predominantly inattentive type or subclinical attention problems, prominently presenting with daydreaming, slowed movement, sluggish response, and daytime drowsiness (positive on the Barkley SCT scale), with or without concurrent stimulant treatment. n=40–60

Primary endpoint

Barkley Cognitive Disengagement Syndrome Scale (SCT/CDS parent version) total score

Secondary endpoints

ESS (child version) sleepiness, SNAP-IV attention subscale, BRIEF executive function, teacher-rated classroom performance, CPT reaction time and variability

Design

Open-label pre-post comparison or randomized controlled trial, 12 weeks

Publication angle

CDS is one of the hottest emerging constructs in child psychiatry internationally over the past five years (recently renamed from SCT to CDS), partially dissociable from ADHD, and poorly responsive to stimulants — precisely the “medication-non-responsive population.” There is almost no clinical research on this domestically, making it one of the most novel directions on this list.

Population

3–12 years of age with ASD, ABC irritability subscale ≥18 or ≥3 emotional outbursts per week, not on antipsychotic medication or on a stable dose. n=30–50

Primary endpoint

ABC Irritability subscale (ABC-I)

Secondary endpoints

ARI Affective Reactivity Index, outburst frequency diary, parenting stress scale (PSI-SF), CGI-I

Design

Open-label pre-post comparison, 12 weeks

Publication angle

First-line medications for ASD irritability (risperidone/aripiprazole) have prominent metabolic side effects that parents resist; there is a clear clinical need for non-pharmacological adjuncts.

Population

3–12 years of age with ASD, CSHQ ≥41 or sleep-onset latency >30 minutes. n=30–50

Primary endpoint

CSHQ total score

Secondary endpoints

Sleep diary, actigraphy (if available in the department), daytime behavioral problems, parental sleep and mood

Design

Open-label pre-post comparison, or randomized controlled trial (control group receives standard sleep hygiene education), 8–12 weeks

Publication angle

Options beyond melatonin are very limited; improvement in parental sleep as a co-primary endpoint is an added strength.

Population

4–16 years of age, with a confirmed epilepsy diagnosis, a stable anti-seizure medication (ASM) regimen for ≥3 months, stable seizure control over the past 3 months, and mood, sleep, or cognitive complaints. n=40–60

Primary endpoint

Cognition (digit span + trail-making test, or WAIS/WISC short form) and BRIEF executive function

Secondary endpoints

SCARED/DSRS-C mood, CSHQ sleep, QOLCE quality of life, caregiver burden

Safety endpoints (key)

Seizure frequency changes, ASM blood levels (if routinely monitored by the department), and ASM dose adjustments — must be explicitly defined and recorded throughout

Design

Open-label pre-post comparison, 12–24 weeks; an “ASM-alone” control arm is recommended to strengthen the evidence

Publication angle

Epilepsy comorbidities are a widely recognized clinical gap domestically; moreover, “the safety of a food supplement in children with epilepsy” is itself an independently publishable paper.

Note

The safety design for this direction must be rigorous; the protocol should be jointly reviewed by the company's medical department and expert advisors.

Population

6–16 years of age with chronic tic disorder or Tourette syndrome, stable treatment regimen. n=30–50

Primary endpoint

YGTSS total score

Secondary endpoints

Comorbid ADHD symptoms (SNAP-IV), obsessive-compulsive symptoms (CY-BOCS), sleep, CGI-I

Design

Open-label pre-post comparison, 12 weeks

Publication angle

Tic disorders fluctuate considerably; extending the baseline observation period by 2–4 weeks to control for natural fluctuation is recommended — this methodological detail can itself become a highlight.

Population

2.5–6 years of age with GDD/language development delay, currently receiving systematic rehabilitation training (≥3 sessions per week). n=30–50

Primary endpoint

Gesell Developmental Schedules or GDS language/adaptive domains

Secondary endpoints

S-S language development assessment, training cooperation score (rated by therapist), sleep, caregiver burden

Design

Parallel-arm comparison against “rehabilitation training alone,” 12–24 weeks

Publication angle

Easiest to conduct in rehabilitation departments — these children already visit the hospital multiple times per week, so follow-up is essentially free and dropout rates are very low.

Note

The lower age limit must match the product's approved age range; confirm with the company before enrollment.

Population

2.5–8 years of age with GDD/ASD/cerebral palsy, currently receiving intensive rehabilitation training ≥3 times per week, with therapists reporting “cooperation drops off quickly later in the session.” n=30–50

Primary endpoint

Effective participation time per training session (stopwatch-timed by therapist, objective and zero-cost) + PedsQL Multidimensional Fatigue Scale, parent version

Secondary endpoints

Training cooperation score, training completion rate, parent-observed post-training fatigue, sleep, Gesell/GDS developmental domains

Design

Parallel-arm comparison against “rehabilitation training alone,” 12 weeks

Publication angle

“Training tolerance” is the ceiling on rehabilitation dosage — training volume determines efficacy, and fatigue determines training volume. No one has systematically studied this causal chain, yet every rehabilitation therapist knows it intimately — this resonates strongly when presented to experts.

Domain positioning: Antidepressants can resolve core mood symptoms, but residual symptoms (cognition, sleep, fatigue, somatization) are the primary drivers of relapse and incomplete functional recovery, and pharmacological options for these are limited. This is Chienomoto's primary battleground.

Population

8–14 years of age, normal intelligence, with reading/writing/math difficulties or executive function complaints, not meeting criteria for ADHD diagnosis. n=40–60

Primary endpoint

BRIEF executive function total score + Continuous Performance Test (CPT, if available)

Secondary endpoints

Academic self-rating, teacher rating, mood and sleep

Design

Randomized controlled trial (waitlist control), 12 weeks

Publication angle

A subclinical population with an easily accessible sample, suitable for journals at the intersection of education and medicine.

Population

Primary caregivers (mostly mothers) of children with ADHD/ASD/GDD, with PSI-SF or ZBI indicating moderate-to-severe burden. n=40–60

Primary endpoint

Caregiver burden scale (PSI-SF / ZBI)

Secondary endpoints

Caregiver PHQ-9, GAD-7, PSQI, family functioning (FAD)

Design

Open-label pre-post comparison or randomized controlled trial, 12 weeks

Publication angle

A reversed perspective with minimal competition. Nursing and psychology journals show high acceptance rates, and enrollment is very fast (parents themselves are highly motivated, with follow-up adherence far exceeding that of pediatric patients).

Population

Ages 6–16, confirmed epilepsy diagnosis, anti-seizure medication (ASM) regimen stable ≥3 months with stable seizure control over the past 3 months; presenting with declining attention, slowed responses, memory decline, or academic slippage (more common among users of topiramate, valproate, or levetiracetam). n=40–60

Primary endpoint

12-week BRIEF parent-rated executive function total score + digit span (working memory)

Secondary endpoints

Trail Making Test A/B or CPT reaction time and variability, teacher-rated classroom performance, PedsQL Multidimensional Fatigue Scale, QOLCE-55 quality of life, change in academic performance

Safety endpoints (key)

Seizure frequency and type changes, ASM dose adjustments, ASM blood levels (if routinely monitored by the department), adverse events

Design

Open-label self pre-post comparison, 12–24 weeks; sites with capacity may add an "ASM-alone" parallel control arm

Publication angle

"The seizures are controlled, but the child has gotten slower" is the most common — and least resolved — complaint in pediatric epilepsy clinics. Switching medication carries relapse risk, and parents are afraid to reduce doses, so clinically there is essentially nothing to do but wait. Cognitive comorbidity as an independent primary endpoint has almost no domestic intervention research behind it.

Division of labor across the four epilepsy directions: K1 cognition and attention (No. 3), K2 medication-related irritability (No. 2), K3 anxiety/depression (No. 2), K4 sleep (No. 2). All four share the same outpatient population and the same baseline assessment battery, and can be run in parallel or combined into a single "epilepsy comorbidity series" proposal.

Population

Ages 4–16 with epilepsy, developing irritability, aggressive behavior, emotional instability, or markedly increased crying after starting levetiracetam (or another ASM), clearly reported by parents or teachers; ASM regimen stable ≥4 weeks with no planned medication change in the near term. n=40–60

Primary endpoint

12-week ABC Irritability subscale (ABC-I) or CBCL externalizing behavior subscale

Secondary endpoints

Emotional outburst frequency diary, SCARED/DSRS-C, CSHQ sleep, parent-child conflict frequency, PSI-SF parenting stress, CGI-I, and the proportion of patients switching or reducing medication due to emotional/behavioral side effects

Safety endpoints (key)

Seizure frequency, ASM dose adjustments and blood levels, serious behavioral events, adverse events

Design

Open-label pre-post comparison, or parallel comparison against "original regimen + standard education," 12 weeks

Publication angle

Levetiracetam's behavioral side effects occur at a non-trivial rate in children and are among the leading reasons for switching or discontinuing medication, and clinically there is almost no second option besides switching drugs (evidence for pyridoxine is weak). "Switching has relapse risk; not switching means the child can't function at school" is the classic dilemma. The "medication-switch rate" endpoint is especially persuasive here — it's a pure clinical-decision endpoint, harder evidence than any rating scale.

Must not imply the ability to prevent or replace a medication-switch decision; when serious behavioral adverse events occur, clinical safety takes priority, with withdrawal per the protocol's pre-specified rules.

Population

Ages 8–16, confirmed epilepsy diagnosis, regimen stable ≥3 months, SCARED or DSRS-C at or above the cutoff; not on antidepressants or on a stable antidepressant regimen ≥8 weeks. n=40–60

Primary endpoint

12-week SCARED anxiety total score (or DSRS-C depression total score, pre-specified based on presenting complaint)

Secondary endpoints

Seizure-related fear and stigma assessment, QOLCE-55 quality of life, school attendance and social avoidance, CSHQ sleep, parental anxiety level

Safety endpoints (key)

Seizure frequency, ASM dose and blood levels, change in antidepressant use, adverse events

Design

Open-label pre-post comparison, or randomized controlled trial (control receives standard health education), 12 weeks

Publication angle

The rate of comorbid anxiety and depression in children with epilepsy is far higher than in the general pediatric population, but pediatric neurologists are generally cautious about prescribing SSRIs to these patients (concerned about seizure threshold and drug interactions), while referral rates to psychiatry remain low — this population effectively falls into a vacuum between two departments, a textbook case of "clear need, clear population, no protocol."

A mood-risk screen must be completed before enrollment; patients with moderate-to-severe depression or self-harm risk are excluded from this study and referred directly to psychiatry, with the referral pathway documented in the protocol.

Population

Ages 4–16 with epilepsy, ASM regimen stable ≥3 months, CSHQ ≥41 or sleep-onset latency >30 minutes; sleep-disordered breathing requiring specialist management already excluded. n=40–60

Primary endpoint

12-week CSHQ total score

Secondary endpoints

Sleep diary (sleep-onset latency, number and duration of night wakings), daytime drowsiness, BRIEF and attention, mood, primary caregiver PSQI

Safety endpoints (key)

Seizure frequency (particularly nocturnal seizures), ASM dose and blood levels, adverse events

Design

Open-label pre-post comparison, or randomized controlled trial (control receives sleep hygiene education), 12 weeks

Publication angle

Sleep and seizures form a bidirectional loop — poor sleep triggers seizures, and seizures plus ASMs in turn disrupt sleep architecture. Everyone in clinical practice knows this loop exists, yet there is almost no non-pharmacological intervention research on it; beyond melatonin there is basically no option, and melatonin use in children with epilepsy itself remains debated.

Nocturnal seizures and ordinary night wakings are easily confused; the protocol must specify criteria for parents to distinguish between them, and video or event recording is recommended.

Population

Ages 5–12 with SeLECTS, seizures controlled or infrequent, but with reading, writing, language, or attention problems (teacher- or parent-reported academic decline). n=30–50

Primary endpoint

BRIEF executive function total score + language/reading ability assessment (or standardized academic score), 24 weeks

Secondary endpoints

WISC short-form working memory and processing speed index, CSHQ sleep, SCARED/DSRS-C mood, teacher-rated classroom performance

Safety endpoints (key)

Seizure frequency, follow-up EEG discharge index (if routinely rechecked by the department), ASM dose adjustments, adverse events

Design

Open-label pre-post comparison, or parallel comparison against "follow-up observation alone," 24 weeks

Publication angle

"Benign" epilepsy isn't actually benign — evidence accumulated over the past decade repeatedly shows this population has clear language and executive-function impairment, and the international classification has already dropped the word "benign." This population has few seizures, follows up regularly, and parental anxiety is entirely focused on schoolwork — a textbook case of high need paired with zero available tools.

The follow-up EEG discharge index is recorded as an observational measure only and must not be used as a basis for judging efficacy or for external claims.

Population

Ages 4–14, EEG discharges markedly improved and condition stable ≥3 months after treatment with steroids, immunoglobulin, or ASMs, but with residual cognitive, language, or behavioral regression. n=15–30 (a rare population; multi-site pooling recommended)

Primary endpoint

24-week Wechsler intelligence scale (or short form) verbal comprehension and full-scale IQ + BRIEF

Secondary endpoints

Language function assessment, adaptive behavior scale (Vineland/ABAS), return-to-school status and academic performance, sleep, caregiver burden

Safety endpoints (key)

Seizure frequency, EEG discharge index, changes in immunotherapy and ASM regimen, adverse events

Design

Prospective cohort + parallel control (control drawn from routine follow-up patients over the same period), 24–48 weeks

Publication angle

Cognitive regression from epileptic encephalopathy is one of the heaviest clinical burdens in pediatric neurology, and once the acute phase has passed there is almost no intervention research targeting "recovery-phase cognitive rebuilding." Single-site sample sizes are scarce, but every major center has an accumulated caseload, making this a natural candidate for multi-site pooling.

This direction must never delay or replace first-line treatments such as steroids or immunoglobulin; enrollment must occur only after acute-phase treatment has concluded. The protocol should be jointly reviewed by the company's medical department and an epilepsy specialty center.

Population

Ages 6–18, confirmed autoimmune encephalitis, acute-phase immunotherapy completed, mRS ≤3 with condition stable ≥1 month, with residual cognitive, attentional, or fatigue symptoms. n=20–40

Primary endpoint

24-week composite cognitive score (Wechsler short form) + BRIEF executive function

Secondary endpoints

mRS and CASE score, PedsQL multidimensional fatigue, return-to-school rate and post-return adjustment, academic performance

Safety endpoints (key)

Relapse events, changes to immunotherapy regimen and steroid dose, infection events, growth and development, adverse events

Design

Prospective cohort + parallel control, 24 weeks (extending cohort follow-up to 12 months recommended)

Publication angle

Acute-phase treatment for pediatric autoimmune encephalitis already has consensus guidelines, but the recovery phase often lasts 1–2 years, and sequelae are the family's greatest source of distress — a phase where clinically there is essentially "nothing to offer." Several major domestic centers have a sizable caseload, yet recovery-phase intervention research is nearly blank.

Coordinate with K8's division of labor: K7 covers cognition and executive function (No. 3), K8 covers psychiatric-behavioral symptoms and sleep-wake disruption (No. 2) — the same cohort can collect both endpoint sets in parallel. The protocol must state clearly that this intervention does not affect or replace immunotherapy; relapse is the primary safety event, requiring pre-specified discontinuation and withdrawal rules.

Population

Ages 6–18, acute-phase immunotherapy for autoimmune encephalitis completed, condition stable ≥1 month, with residual irritability, emotional instability, stereotyped behavior, or circadian rhythm reversal. n=20–40

Primary endpoint

12–24 week CBCL externalizing behavior subscale + CSHQ sleep total score

Secondary endpoints

Sleep-wake rhythm recording (sleep diary or actigraphy), ABC Irritability subscale, dose changes in antipsychotic and sedative-hypnotic medications, mRS, caregiver burden and sleep

Safety endpoints (key)

Relapse events, changes to immunotherapy and psychiatric medication regimen, metabolic indicators (in patients on long-term antipsychotics), adverse events

Design

Prospective cohort + parallel control, 24 weeks

Publication angle

What truly wears families down in the recovery phase of anti-NMDAR encephalitis is often not cognition but behavioral disruption and a reversed day-night cycle — and clinically this phase is managed almost entirely by pushing through with antipsychotics and sedatives, which are very difficult to taper. Using "reduction in psychiatric medication dose" as a secondary endpoint is more persuasive than any rating scale.

Population

Ages 3–16, acute phase concluded ≥1 month, with residual consciousness, cognitive, motor, or behavioral impairment, currently receiving systematic rehabilitation training; includes patients fed via nasogastric tube. n=30–50

Primary endpoint

24-week WeeFIM (Functional Independence Measure for Children) or GMFM-66 (chosen based on the predominant impairment type)

Secondary endpoints

Cognitive/developmental scale (Wechsler short form or Gesell), effective rehabilitation-session participation time (therapist-timed), alertness, CSHQ sleep, caregiver burden

Safety endpoints (key)

Seizures, feeding tolerance and aspiration events, growth curves, infection, adverse events

Design

Parallel control against "rehabilitation training alone," 24 weeks

Publication angle

Encephalitis sequelae are among the leading causes of acquired disability in Chinese children; the recovery period is long, the assessment framework already exists, and follow-up dropout is nearly zero. The fact that No. 5 can be tube-fed makes it the only product line on the entire list able to enter the critical-care and feeding-tube pathway — a route no other functional food can access.

Pediatric dosing must follow medical guidance and be pre-fixed in the protocol; tube feeding requires specified preparation and flushing procedures, with feeding tolerance recorded at every session.

Population

Ages 3–16, disorder of consciousness (VS/MCS) from encephalitis, hypoxic-ischemic injury, trauma, or post-surgery, condition stable ≥4 weeks, mostly tube-fed. n=15–30

Primary endpoint

24-week change in CRS-R (Coma Recovery Scale-Revised) total score and consciousness-state transition (VS→MCS→emergence from MCS)

Secondary endpoints

Daily wakefulness duration recording, rehabilitation-session participation time, complication rate, family burden and psychological state

Safety endpoints (key)

Feeding tolerance, aspiration and aspiration pneumonia, seizures, infection, growth and development, adverse events

Design

Prospective single-arm, or parallel control against "standard arousal rehabilitation alone," 24 weeks

Publication angle

Arousal-promoting options for pediatric DOC are extremely scarce, and nutrition/functional-food research in this space is essentially blank. CRS-R is an internationally recognized endpoint, and a well-conducted case series alone would be publishable.

This is the most ethically sensitive direction on the list: subjects cannot provide independent informed consent, so a guardian must sign, and an independent safety monitoring process is required. It is recommended that only centers already experienced with pediatric DOC arousal care take this on, with the protocol jointly reviewed by the company's medical department.

Population

Ages 6–16, 1–6 months after moderate-to-severe TBI, vital signs stable, with cognitive, fatigue, irritability, or sleep problems. n=30–50

Primary endpoint

12–24 week BRIEF executive function + PedsQL Multidimensional Fatigue Scale

Secondary endpoints

WISC short-form processing speed and working memory, CBCL behavior, CSHQ sleep, WeeFIM, return-to-school rate and post-return adjustment

Safety endpoints (key)

Post-traumatic seizures, worsening headache, abnormal follow-up imaging, adverse events

Design

Open-label pre-post comparison, or parallel comparison against "rehabilitation training alone," 12–24 weeks

Publication angle

Post-TBI fatigue and executive-function impairment are the leading cause of failed return to school in children. The adult TBI literature is extensive, but pediatric data are seriously lacking. Paired with S10 (brain trauma and post-neurosurgical rehabilitation), this forms an adult-pediatric matched pair of directions, and the same cross-department hospital can share a single protocol and set of scales.

Population

Ages 4–16, 1–6 months after moyamoya revascularization surgery, or 1–6 months after pediatric arterial ischemic stroke, condition stable and currently in rehabilitation. n=20–40

Primary endpoint

24-week Wechsler short-form composite cognitive score + PedsQL quality of life

Secondary endpoints

BRIEF executive function, WeeFIM/GMFM, PedsQL multidimensional fatigue, return-to-school status, caregiver burden

Safety endpoints (key)

New stroke or TIA events, seizures, follow-up imaging and perfusion studies, adverse events

Design

Prospective cohort + parallel control, 24 weeks

Publication angle

China performs one of the highest volumes of pediatric moyamoya surgery in the world, yet post-surgical cognitive follow-up data are extremely scarce — "how much cognitive recovery can be expected after surgery" is the question parents care about most and that no one answers. A cohort of this kind has independent publication value on its own.

New cerebrovascular events are the primary safety endpoint, and withdrawal and reporting rules must be co-defined with neurosurgery; imaging follow-up should proceed per the existing clinical protocol and not be altered for the study.

Population

Ages 8–16, meets ICHD-3 migraine diagnostic criteria, confirmed via a 4-week baseline headache diary to have ≥4 headache days per month; preventive treatment regimen stable ≥4 weeks, or no preventive medication in use. n=40–60

Primary endpoint

12-week PedMIDAS pediatric migraine disability score + CSHQ sleep total score

Secondary endpoints

Monthly headache days and acute-medication days (headache diary), SCARED/DSRS-C mood, BRIEF attention and executive function, missed school days, PedsQL

Safety endpoints

Headache worsening events, acute-medication overuse, adverse events

Design

4-week baseline diary + 12-week open-label pre-post comparison, or randomized controlled trial (control receives standard headache hygiene education)

Publication angle

The evidence base for preventive medications in pediatric migraine is itself weak — large randomized trials have shown amitriptyline and topiramate to be no better than placebo, which is why guidelines increasingly emphasize non-pharmacological and lifestyle management, lending real legitimacy to an "adjunct support" positioning. Meanwhile, sleep, anxiety, and attention comorbidities occur at very high rates in pediatric migraine, yet are rarely treated as endpoints in their own right.

The primary endpoint is deliberately not set on headache days, but on disability and comorbidity burden; headache days are recorded only as a secondary endpoint. This maintains the compliance boundary of a food product making no analgesic/preventive efficacy claims, while also aligning with the international trend toward "function as the endpoint."

Population

Ages 3–14 with cerebral palsy (any GMFCS level I–V), CSHQ ≥41 or parent-reported ≥3 night wakings per week; spasticity and pain management regimen stable ≥4 weeks. n=30–50

Primary endpoint

12-week CSHQ total score (or SDSC Sleep Disturbance Scale for Children)

Secondary endpoints

Sleep diary (sleep-onset latency, number and duration of night wakings), daytime behavior and training cooperation, pain score, primary caregiver PSQI and ZBI

Safety endpoints

Seizures (comorbid epilepsy is common in cerebral palsy), feeding and bowel movements, growth and development, adverse events

Design

Open-label pre-post comparison, or randomized controlled trial (control receives sleep hygiene education), 12 weeks

Publication angle

Sleep problems occur at very high rates in children with cerebral palsy, yet available options are essentially limited to melatonin; and it's really the caregiver who gets worn down by the night wakings. Making parental sleep a co-endpoint is a highly receptive angle for journals at the intersection of rehabilitation and nursing. Clear division of labor with D12: D12 looks at daytime training tolerance, this direction looks at the night.

Population

Ages 8–18, narcolepsy (type 1/2) or idiopathic hypersomnia confirmed by polysomnography and MSLT, medication regimen stable ≥8 weeks with residual daytime sleepiness. n=15–30

Primary endpoint

12-week ESS-CHAD (Epworth Sleepiness Scale for Children and Adolescents)

Secondary endpoints

KSS multi-timepoint alertness self-rating, classroom drowsiness and missed school days, BRIEF, mood, weight change

Safety endpoints (key)

Cataplexy frequency, original-drug dose changes, cardiovascular-related adverse events, adverse events

Design

Open-label self pre-post comparison, 12 weeks

Publication angle

Diagnostic delay is common in pediatric narcolepsy, medication choice is limited by age with prominent side effects, and residual sleepiness has almost no supplementary options. Arousal support is core territory for No. 5, but this direction must be led by a sleep center.

It must never be implied in any form that this can replace treatment with modafinil, sodium oxybate, or similar medications; the protocol must state clearly that the original medication is neither reduced nor discontinued during the study period.

Population

Ages 6–16 with confirmed neuromuscular disease (primarily DMD), glucocorticoid regimen stable ≥3 months, currently receiving regular rehabilitation training. n=20–40

Primary endpoint

12–24 week PedsQL Neuromuscular Module fatigue domain + effective participation time per training session (therapist-recorded)

Secondary endpoints

BRIEF executive function and attention, 6-minute walk distance or NSAA (depending on disease stage), CSHQ sleep, academic performance and mood

Safety endpoints (key)

Weight and body composition changes (in steroid-treated patients), cardiopulmonary follow-up, fall events, adverse events

Design

Open-label pre-post comparison, 12–24 weeks

Publication angle

Cognitive and behavioral comorbidities in DMD have long been overlooked (linked to dystrophin isoform expression in the brain), while fatigue directly caps the achievable dose of rehabilitation training. Rare-disease parent communities are highly organized, so enrollment and follow-up are actually smoother here than in more common conditions.

Explicitly not designed with motor function or disease-course change as the primary endpoint; weight and metabolic changes in steroid-treated patients must be recorded separately to avoid confounded attribution.

Population

Ages 6–18, intracranial tumor (medulloblastoma, glioma, etc.), ≥6 months after completing surgery and/or chemoradiotherapy, no active disease, with declining attention, memory, processing speed, or academic difficulties. n=30–50

Primary endpoint

24-week Wechsler short-form processing speed and working memory index + BRIEF

Secondary endpoints

PedsQL Brain Tumor Module, PedsQL multidimensional fatigue, CSHQ sleep, mood, return-to-school status and academic performance

Safety endpoints (key)

Tumor follow-up imaging and relapse events, post-radiotherapy endocrine function, growth curves, adverse events

Design

Open-label pre-post comparison, or parallel comparison against "routine follow-up alone," 24 weeks

Publication angle

Pediatric brain-tumor survival rates have risen markedly, making cognitive sequelae a core long-term outcome issue, yet intervention options remain scarce. Paired with domain O (oncology supportive care), this forms an adult-pediatric matched pair of directions; the follow-up systems in pediatric oncology and neurosurgery are already comprehensive, keeping the marginal cost of data collection very low.

Enrollment requires confirmation of no active disease from the oncology specialty team; imaging follow-up should proceed on the existing tumor-surveillance schedule and not be altered for the study.

Population

Ages 4–16, under regular follow-up in pediatric neurology for any chronic condition (epilepsy, cerebral palsy, encephalitis sequelae, chronic headache, neuromuscular disease, neurogenetic disease, etc.), primary condition stable ≥3 months, with SCARED/DSRS-C or CSHQ at or above the cutoff on either measure. n=60–100, stratified by primary condition

Primary endpoint

12-week composite mood score (SCARED + DSRS-C) and CSHQ sleep total score, co-primary endpoints

Secondary endpoints

QOLCE-55 or PedsQL quality of life, school attendance, BRIEF, PSI-SF parenting stress, CGI-I; subgroup analysis stratified by primary condition

Safety endpoints (key)

Primary-disease activity indicators (seizure frequency, relapse, headache days, etc., pre-specified separately by disease), original-drug dose adjustments and blood levels, adverse events

Design

Prospective cohort + parallel or randomized control, 12 weeks; direct linkage to the X1 multi-site unified registry recommended

Publication angle

This is the fastest-recruiting direction in the entire domain — it doesn't discriminate by disease, and pediatric neurology clinics generate eligible cases every single day. Mood and sleep comorbidity is a burden shared across all chronic neurological conditions in children, yet it has always been fragmented by disease and never studied as a combined whole. The cross-disease design is itself a methodological selling point, and stratified analysis can yield multiple subgroup conclusions from a single study.

Because this crosses disease categories, safety endpoints must be pre-specified separately by disease, the protocol needs a disease-by-safety-indicator matrix, not a vague catch-all like "primary disease worsening." This is the key to whether the direction can pass ethics review.

Population

18–60 years of age with MDD, on a stable antidepressant regimen for ≥8 weeks, HAMD-17 ≤10 (clinical remission or partial remission), but with subjective cognitive complaints (PDQ-5-D ≥ cutoff). n=50–80

Primary endpoint

12-week change in THINC-it composite score or DSST (Digit Symbol Substitution Test)

Secondary endpoints

PDQ-5-D subjective cognition, TMT-A/B, HAMD-17, SDS Sheehan Disability Scale, return-to-work/return-to-school status

Design

Randomized double-blind placebo-controlled trial (preferred) or open-label controlled trial, 12 weeks

Publication angle

Residual cognitive symptoms are an international hotspot (CANTAB/THINC-it are now standard tools), and domestic data on non-pharmacological interventions are very scarce; an analytical angle contrasting subjective vs. objective cognitive dissociation is likely to stand out.

Population

18–60 years of age with MDD, on a stable antidepressant regimen for ≥8 weeks, with partial remission on HAMD but prominently presenting with “no interest, no motivation to move, no energy,” AES ≥34 or SHAPS indicating anhedonia. n=40–60

Primary endpoint

AES Apathy Evaluation Scale or SHAPS Anhedonia Scale

Secondary endpoints

TEPS anticipatory/consummatory pleasure, Behavioral Activation for Depression Scale (BADS), HAMD (as a covariate for adjustment), SDS functional disability, return-to-work/return-to-school status

Design

Open-label pre-post comparison or randomized controlled trial, 12 weeks

Publication angle

Anhedonia and loss of motivation are among the dimensions most resistant to antidepressant treatment (SSRIs may even worsen them), and are a direct cause of incomplete functional recovery. Framing “apathy improvement independent of mood improvement” as the core analysis gives the study substantial academic weight.

Population

18–55 years of age with MDD, on SSRI treatment with mood symptoms in remission, but reporting “my emotions have gone flat — I can't feel happy or sad, I just don't care about anything.” n=40–60

Primary endpoint

OQESA (Oxford Questionnaire on the Emotional Side-effects of Antidepressants)

Secondary endpoints

AES apathy, SHAPS, sexual function and other SSRI side effects, SSRI self-discontinuation rate and adherence, HAMD (to ensure no worsening)

Design

Open-label pre-post comparison or randomized controlled trial, 12 weeks

Publication angle

This is a severely underestimated clinical problem — reported rates of emotional blunting run as high as 40–60%, and it is one of the leading reasons patients discontinue medication on their own, yet there are almost no available interventions. Setting “discontinuation rate” as a co-primary endpoint directly links symptom improvement to relapse prevention. Domestic research is essentially blank, and I personally believe this is one of the directions on this entire list with the greatest potential to “make a splash.”

Population

MDD patients whose HAMD has remitted after treatment but with prominent fatigue/low energy. n=40–60

Primary endpoint

FSS Fatigue Severity Scale or MFI-20

Secondary endpoints

PHQ-15, SDS functioning, work productivity (WPAI)

Design

Open-label pre-post comparison, 12 weeks

Publication angle

Fatigue is the most common yet least-measured residual symptom, and is directly linked to relapse risk.

Population

Patients on more sedating antidepressants such as mirtazapine, paroxetine, or trazodone, reporting daytime fatigue and grogginess. n=40–60

Primary endpoint

FSS Fatigue Severity Scale or MFI-20

Secondary endpoints

ESS sleepiness, daytime functioning (WPAI work productivity), rate of antidepressant dose reduction or switching, HAMD (to ensure no worsening), adherence

Design

Open-label pre-post comparison, 12 weeks

Publication angle

Drug-induced fatigue is a textbook case of “curing the illness but ruining daily life,” and a leading reason for switching or discontinuing medication; approaching it from the angle of adverse-effect management gives the study a clean rationale and simple ethics.

Domain positioning: This is the area with the strongest data foundation from the original Japanese research product, and also the domestic memory clinic population easiest to enroll. It is recommended to focus on both early-stage (SCD/MCI) and BPSD/caregiver burden — the former offers a large sample size and fast recruitment, while the latter addresses the sharpest clinical pain point.

Population

18–65 years of age with MDD and comorbid insomnia, ISI ≥15, stable antidepressant regimen. n=40–60

Primary endpoint

ISI Insomnia Severity Index

Secondary endpoints

PSQI, sleep diary, change in hypnotic dose (including benzodiazepines/Z-drugs), HAMD sleep factor, daytime fatigue

Design

Open-label pre-post comparison or randomized controlled trial, 8–12 weeks

Publication angle

Setting “hypnotic dose reduction” as a co-primary endpoint — de-benzodiazepination is currently a shared policy and clinical priority in China, and this angle significantly raises the value of the paper.

Population

Ages 12–18 with MDD, newly initiated on an SSRI (≤7 days). n=50–80

Primary endpoint

Trajectory of HAMD/CDI change within 6 weeks of initiation, and “time to onset of response”

Secondary endpoints

ARI irritability, agitation/akathisia, sleep, NSSI behavior frequency, early SSRI discontinuation rate

Safety endpoints

Activation syndrome and changes in suicidal ideation (C-SSRS) must be monitored throughout

Design

Randomized controlled (SSRI + Chienomoto vs. SSRI alone), 6–12 weeks

Publication angle

The window before SSRIs take effect is the highest-risk period for adolescent depression and also the period with the highest discontinuation rate, yet almost no intervention studies address it

Note

Involves a population at risk of suicide; ethical requirements are stringent — recommended only for centers with an adolescent psychiatric ward and an established crisis-response protocol

Population

Ages 12–18 with NSSI behavior, receiving standardized treatment. n=30–50

Primary endpoint

NSSI behavior frequency (Self-Injury Log / OSI)

Secondary endpoints

DERS Difficulties in Emotion Regulation Scale, ARI irritability, impulsivity (BIS-11), sleep

Design

Open-label, pre-post comparison, 12 weeks

Publication angle

NSSI is currently among the most widely discussed topics in adolescent mental health; an emotion-regulation-mechanism perspective offers more depth than a purely symptom-based one

Note

High-risk population; ethical and safety-protocol requirements are stringent

Population

Ages 18–55, BD-I/II in remission (YMRS ≤7 and HAMD ≤8 sustained ≥8 weeks), mood stabilizer regimen stable. n=40–60

Primary endpoint

24-week change in cognition (MCCB brief version, or Digit Symbol + TMT + verbal fluency)

Secondary endpoints

BRIAN Biological Rhythms Interview, PSQI, FAST functional assessment, quality of life

Safety endpoints (key)

YMRS and ASRM must be monitored throughout to track risk of switching into mania; every mood-episode event must be individually documented

Design

Open-label, pre-post comparison, 24 weeks (the cognitive endpoint requires a longer observation period)

Publication angle

Cognitive impairment during bipolar remission is the core driver of incomplete functional recovery, and no effective medication exists for it; moreover, safety data showing that “an adjunctive supplement does not trigger a switch into mania” carries independent publication value in its own right

Note

Risk of switching into mania is the greatest scientific and compliance risk in this direction; the protocol must include clearly defined stopping rules

Population

Age ≥60 with depressive disorder, GDS-15 ≥8, MoCA 18–25 (suggesting mild cognitive impairment), antidepressant regimen stable. n=40–60

Primary endpoint

Co-primary endpoints: MoCA + GDS-15

Secondary endpoints

AVLT auditory verbal learning, daily functioning (IADL), sleep, fall events

Design

Open-label, pre-post comparison, 24 weeks

Publication angle

Late-onset depression is a prodromal manifestation of dementia; the intervention window along the “depression–dementia continuum” has been a hot topic in recent years, and findings can be published across geriatrics, psychiatry, and neurology

Population

Ages 18–65 with GAD or an anxiety disorder, HAMA ≥14, regimen stable. n=40–60

Primary endpoint

HAMA total score (can be broken down into somatic and psychic factors)

Secondary endpoints

GAD-7, PHQ-15 somatization, PSQI, change in benzodiazepine dosage

Design

Open-label, pre-post comparison, 8–12 weeks

Publication angle

The somatization subtype of anxiety responds poorly to medication and presents across scattered departments (gastroenterology, cardiology) — an underappreciated population

Population

Depressed patients undergoing a course of rTMS or MECT. n=30–50

Primary endpoint

HAMD response rate at end of course / post-MECT cognitive recovery (MMSE, AVLT)

Secondary endpoints

Treatment-related adverse effects (headache, memory impairment), sleep, course completion rate

Design

Randomized controlled, spanning the entire treatment course plus a 4-week follow-up

Publication angle

Nutritional protection against post-MECT cognitive impairment is a highly novel angle that very few researchers in China have pursued

Population

Age ≥55 with memory complaints but normal objective cognition (MoCA ≥26, CDR=0). n=60–100

Primary endpoint

SCD-Q / MAC-Q subjective cognition questionnaire; objective memory (AVLT) as a co-primary endpoint

Secondary endpoints

HADS anxiety/depression, sleep, quality of life, cognition-related healthcare-seeking behavior

Design

Randomized controlled (control arm: health education), 24 weeks

Publication angle

SCD is the largest yet least-studied population in memory clinics, with recruitment far faster than MCI/AD; a “subjective–objective dissociation” analysis carries theoretical depth

Population

Age ≥55, meeting Petersen MCI criteria, MoCA 18–25, CDR=0.5. n=50–80

Primary endpoint

24-week change in ADAS-Cog or MoCA

Secondary endpoints

AVLT delayed recall, TMT, daily functioning (FAQ), mood, sleep, rate of conversion to dementia (long-term follow-up)

Design

Randomized controlled (open-label or double-blind), 24 weeks, with follow-up recommended to be extended to 12 months

Publication angle

MCI intervention is a global hotspot; retaining the cohort for a 12-month conversion-rate follow-up would multiply the study's value

Population

Mild-to-moderate AD, stable on donepezil/memantine for ≥3 months, MMSE 10–24. n=40–60

Primary endpoint

ADAS-Cog (or MMSE)

Secondary endpoints

ADCS-ADL activities of daily living, NPI-Q, CDR-SB, caregiver burden (ZBI)

Design

Open-label self pre-post comparison or parallel-arm comparison, 24 weeks

Publication angle

Cognitive endpoints in AD are unlikely to show significant change within 24 weeks; ADL and NPI are recommended as co-primary endpoints instead, offering both a higher probability of success and greater clinical significance

Population

Dementia of any type with BPSD, NPI-Q total score ≥6 or prominent agitation subscale. n=40–60

Primary endpoint

NPI-Q total score and agitation/irritability subscale

Secondary endpoints

CMAI agitation inventory, change in antipsychotic dosage, caregiver burden (ZBI), risk of institutionalization

Design

Open-label, pre-post comparison, 12 weeks

Publication angle

BPSD is the most painful pain point in dementia care — antipsychotics carry a black-box warning and guidelines emphasize non-pharmacological approaches first; demonstrating an “antipsychotic dose reduction” would be an extremely strong publication selling point

Population

Mild-to-moderate AD, VCI, or PDD, with a prominent NPI apathy subscale or AES-I (caregiver version) ≥38, cholinesterase inhibitor regimen stable. n=40–60

Primary endpoint

AES-I Apathy Evaluation Scale (caregiver version) or NPI apathy subscale

Secondary endpoints

Daily activity engagement (caregiver activity diary), ADCS-ADL, cognition (MoCA/ADAS-Cog), depression (CSDD Cornell Scale for Depression in Dementia, for differential purposes), caregiver burden (ZBI)

Design

Open-label, pre-post comparison, 12–24 weeks

Publication angle

Apathy is the most prevalent BPSD in dementia (50–70%), more common than agitation, yet the least studied — because it is “quiet,” families don't complain about it and physicians don't prescribe for it. Yet it directly determines whether patients remain willing to stay active, socialize, and participate in rehabilitation, and it is also the deepest source of caregivers' sense of helplessness. No approved treatment currently exists. This direction offers extremely high clinical value and very little competition

Population

Dementia with nighttime awakenings, day-night reversal, or evening agitation. n=30–50

Primary endpoint

Sleep diary (caregiver-recorded) total sleep time and number of nighttime awakenings; or actigraphy-derived rhythm parameters

Secondary endpoints

Sundowning episode frequency, NPI nighttime-behavior subscale, caregiver sleep and burden, hypnotic drug use

Design

Open-label, pre-post comparison, 8–12 weeks

Publication angle

Sundowning directly determines whether families can continue providing home care and is the leading trigger for institutionalization — its clinical significance is very strong

Population

Probable DLB, regimen stable. n=20–40 (rare disease; case series acceptable)

Primary endpoint

NPI hallucination subscale + cognitive fluctuation scale (CAF / MFC)

Secondary endpoints

RBDSQ, MoCA, UPDRS-III, fall events, antipsychotic sensitivity events

Design

Open-label pre-post comparison or prospective case series, 12–24 weeks

Publication angle

DLB patients are highly sensitive to antipsychotics (which can trigger neuroleptic malignant syndrome), and treatment options are extremely limited; even a case series with n=20 carries publication value

Population

PD with cognitive complaints, meeting MDS PD-MCI criteria, anti-Parkinsonian regimen stable. n=40–60

Primary endpoint

MoCA / PD-CRS Parkinson's Disease Cognitive Rating Scale

Secondary endpoints

MDS-UPDRS-I (non-motor symptoms), RBDSQ, PDSS-2 sleep, depression, quality of life (PDQ-39)

Design

Open-label, pre-post comparison, 24 weeks

Publication angle

Non-motor symptoms of PD (cognition, sleep, mood) are a mainstream focus of current PD research, leaving substantial room beyond motor symptoms

Population

VCIND or mild vascular dementia, ≥3 months post-stroke, secondary prevention regimen stable. n=40–60

Primary endpoint

MoCA + executive function (TMT-B, Stroop)

Secondary endpoints

Apathy, depression, daily functioning, recurrence events

Design

Open-label, pre-post comparison, 24 weeks

Publication angle

VCI is dominated by executive-function impairment (as distinct from the memory impairment of AD); choosing the right cognitive assessment tool is the key to success

Population

Behavioral-variant FTD. n=15–30

Primary endpoint

FBI Frontal Behavioral Inventory / NPI disinhibition and apathy subscales

Secondary endpoints

CBI-R, caregiver burden, cognition (frontal executive function)

Design

Prospective case series, 24 weeks

Publication angle

No approved treatment exists for FTD; case series on rare diseases have a reliable place for publication in specialty journals

Population

Age ≥65, community-dwelling or outpatient older adults, FRAIL scale score 1–3 (pre-frail/frail), core complaint includes fatigue. n=50–80

Primary endpoint

FRAIL scale score or Fried frailty phenotype grading

Secondary endpoints

Grip strength, 4-meter gait speed, SPPB Short Physical Performance Battery, FSS fatigue, MNA-SF nutritional status, fall and hospitalization events, cognition and mood

Design

Randomized controlled (control arm: exercise + nutrition education), 24 weeks

Publication angle

Fatigue is one of the five core criteria in the Fried frailty phenotype; frailty is currently the leading discipline in geriatric medicine, directly linked to disability, hospitalization, and mortality. Geriatrics, general practice, or rehabilitation medicine can all lead the study, and findings can be published in both geriatric-medicine and clinical-nutrition journals

Field Positioning: Psychiatric inpatient/day rehabilitation wards are the research setting with the highest adherence and follow-up completeness (patients are concentrated, medication administration can be supervised, and dropout rates are extremely low). The recommended primary focus is negative symptoms, cognitive impairment, and tapering of sedative medications.

Population

Primary caregivers of patients with moderate-to-severe dementia, ZBI ≥21. n=40–60

Primary endpoint

ZBI Zarit Burden Interview

Secondary endpoints

Caregiver PHQ-9, GAD-7, PSQI, quality of life, caregiver's own cognitive complaints

Design

Randomized controlled (control arm: standard caregiving education), 12 weeks

Publication angle

High acceptance rate in nursing journals; fast recruitment and good adherence; can also be conducted as a parallel sub-study alongside the A4/A8 directions

Population

Ages 18–55, schizophrenia in a stable phase, antipsychotic regimen stable ≥8 weeks, PANSS negative subscale ≥15. n=50–80

Primary endpoint

PANSS negative subscale or SANS

Secondary endpoints

MCCB / BACS cognitive battery, PSP personal and social performance, CGI-S, positive symptoms (safety observation)

Safety endpoints

Positive-symptom worsening events, hospitalization events

Design

Randomized controlled (open-label or double-blind), 12–24 weeks

Publication angle

Negative symptoms and cognitive impairment represent the greatest unmet need in schizophrenia and are the core determinants of social functioning; adjunctive intervention research has clear room to grow domestically

Population

Ages 18–55, clinically stable schizophrenia, antipsychotic regimen stable for ≥8 weeks, BNSS or CAINS indicating prominent impairment in the motivation-pleasure dimension. n=40–60

Primary endpoint

BNSS (Brief Negative Symptom Scale) "Motivation-Pleasure" factor, or CAINS-MAP

Secondary endpoints

MAP-SR self-reported motivation and pleasure, daily activity logs (behavioral indicators), PSP social functioning, PANSS negative subscale, cognition

Design

Randomized controlled trial, 12–24 weeks

Publication angle

Negative symptoms have been clearly separated into two independent factors — "diminished expression" and "diminished motivation-pleasure" — with the latter being a stronger predictor of functional outcomes and showing a poorer pharmacological response. Using next-generation instruments such as BNSS/CAINS rather than PANSS-N as the primary endpoint is itself methodologically advanced.

Population

Patients on strongly sedating antipsychotics such as quetiapine, clozapine, or olanzapine, with ESS ≥10 or self-reported daytime drowsiness affecting functioning. n=40–60

Primary endpoint

ESS (Epworth Sleepiness Scale)

Secondary endpoints

FSS fatigue, daytime alertness (KSS at multiple time points), cognition (reaction time, sustained attention), rate of self-discontinuation of antipsychotics and adherence, PSP functioning, psychiatric symptoms (to confirm no worsening)

Design

Randomized controlled trial, 12 weeks

Publication angle

Daytime sedation is the single biggest threat to antipsychotic adherence and a direct barrier to patients returning to work and social life; in clinical practice, physicians are typically left with only two options — "switch medication or endure it." Making adherence a co-primary endpoint links the intervention directly to relapse risk.

Field positioning: The subacute inpatient window in rehabilitation medicine (2 weeks–3 months post-onset) is an ideal research setting — patients are in hospital daily, assessments are performed routinely by therapists, and follow-up has zero attrition. It is recommended to prioritize the three drug-free directions: "post-stroke cognition, fatigue, and apathy."

Population

Chronic patients hospitalized for ≥1 year, on a stable treatment regimen. n=50–80

Primary endpoint

PANSS total score + PSP functioning

Secondary endpoints

Cognition, sleep, self-care ability, Nurses' Observation Scale for Inpatient Evaluation (NOSIE), body weight and metabolic indicators

Design

Randomized controlled trial, 24 weeks

Publication angle

The highest feasibility in the entire catalog — medication intake can be supervised, follow-up has zero attrition, assessments are completed by ward nurses, and there is no risk of loss to follow-up. Well suited as the first collaboration project with a psychiatric specialty hospital.

Population

First-episode patients, ≤3 months since antipsychotic initiation, ages 18–35. n=40–60

Primary endpoint

Change in MCCB cognitive battery at 24 weeks

Secondary endpoints

PANSS, PSP, rate of return to school/work, analysis related to duration of untreated psychosis (DUP)

Design

Randomized controlled trial, 24 weeks

Publication angle

The "cognitive trajectory" during the first-episode period is a central topic in early intervention research worldwide.

Population

Psychiatric inpatients on long-term benzodiazepines or Z-drugs for sleep, willing to taper. n=40–60

Primary endpoint

Magnitude of reduction in daily benzodiazepine-equivalent dose (diazepam equivalents)

Secondary endpoints

PSQI, ISI, taper success rate, withdrawal-related symptoms, fall events, daytime sleepiness

Design

Randomized controlled trial (standard tapering protocol ± Chienomoto), 12 weeks

Publication angle

Benzodiazepine de-prescribing is a shared policy direction both in China and internationally. Linking an adjunctive intervention to taper success rate makes this one of the strongest publication angles in this catalog; an associated analysis of fall risk in elderly patients would further strengthen it.

Population

OCD patients with residual symptoms after an adequate dose and duration of SSRI treatment, Y-BOCS ≥16. n=30–50

Primary endpoint

Y-BOCS total score

Secondary endpoints

Anxiety and depression, sleep, functioning, quality of life

Design

Open-label, pre-post comparison, 12 weeks

Publication angle

OCD has a low treatment response rate and a high residual symptom rate, with little existing research on adjunctive approaches.

Population

Patients on closed (locked) psychiatric wards. n=50–100

Primary endpoint

Incidence of nighttime adverse events (falls, impulsive behavior, frequency of restraint use)

Secondary endpoints

NOSIE (Nurses' Observation Scale), nursing workload records, patient sleep

Design

Pre-post comparison (ward-level) or randomized controlled trial, 12 weeks

Publication angle

Nursing-team led, with low competition, and high acceptance rates at core nursing journals; data are drawn from routine ward records, so collection cost is nearly zero.

Population

2 weeks–6 months after a first stroke, MoCA <26, currently receiving cognitive rehabilitation training. n=50–80

Primary endpoint

Change in MoCA or LOTCA at 12–24 weeks

Secondary endpoints

Executive function (TMT-B, Stroop), AVLT, MBI activities of daily living, mRS

Design

Randomized controlled trial (standard rehabilitation ± Chienomoto), 12–24 weeks

Publication angle

PSCI has an incidence as high as 30–60%, guideline recommendations remain weak, and it is the mainstream research direction in rehabilitation medicine.

Population

1–6 months after stroke, HAMD-17 ≥8 or PHQ-9 ≥5. n=40–60

Primary endpoint

HAMD-17 or PHQ-9

Secondary endpoints

Engagement and cooperation with rehabilitation training, MBI, fatigue, sleep, rate of antidepressant initiation

Design

Randomized controlled trial, 12 weeks

Publication angle

PSD directly affects adherence to rehabilitation training; setting "training engagement" as a secondary endpoint links mood improvement to functional recovery, giving the study a more complete logical narrative.

Population

≥1 month after stroke, FSS ≥4 or FAS ≥22. n=40–60

Primary endpoint

FSS (Fatigue Severity Scale)

Secondary endpoints

Rehabilitation training tolerance duration (objective measure), 6-minute walk distance, mood, sleep, quality of life

Design

Randomized controlled trial, 12 weeks

Publication angle

There is currently no effective pharmacological treatment for post-stroke fatigue; guidelines can only recommend non-pharmacological approaches — this is one of the most legitimately justified indications for a functional-food positioning.

Population

1–6 months after stroke, AES (Apathy Evaluation Scale) indicating apathy, to be differentiated from depression. n=30–50

Primary endpoint

AES (Apathy Evaluation Scale)

Secondary endpoints

Initiative in rehabilitation training (therapist-rated), executive function, MBI, caregiver burden

Design

Open-label pre-post comparison or randomized controlled trial, 12 weeks

Publication angle

Distinguishing apathy from depression has been a hot topic in recent years, with very little domestic research; apathy is the largest hidden barrier to rehabilitation training, and it resonates strongly with clinicians.

Population

2 weeks–6 months after stroke, ESS ≥10, or frequent drowsiness and insufficient alertness during rehabilitation training (more common with thalamic, brainstem, or frontal lobe lesions). n=40–60

Primary endpoint

ESS (Epworth Sleepiness Scale)

Secondary endpoints

Alertness during rehabilitation training sessions (KSS at multiple time points before/after training), effective training duration, MoCA, AES apathy (for differentiation), PSQI (to rule out insufficient nighttime sleep), MBI

Design

Randomized controlled trial, 12 weeks

Publication angle

Post-stroke sleepiness directly eats into the effective time available for rehabilitation training, yet it has almost never been studied as a standalone endpoint; together with S3 (fatigue) and S5 (apathy), it forms a "low-arousal triad" — the three directions can be run in parallel within the same department using a shared assessment framework.

Field positioning: This is the field with the least competition, the fastest recruitment, and the lowest ethical risk. The core entry point should be "the population unwilling or unsuited to use hormone therapy (MHT)" — a group that gynecology outpatient clinics face every day without being able to offer a solution.

Population

Post-stroke insomnia or disrupted sleep architecture, PSQI >7. n=40–60

Primary endpoint

PSQI / ISI

Secondary endpoints

Sleep diary, hypnotic medication use, daytime rehabilitation training performance, fatigue, cognition

Design

Randomized controlled trial, 8–12 weeks

Publication angle

Post-stroke sleep disturbance affects neuroplasticity and functional recovery, giving the study a complete mechanistic narrative.

Population

Inpatient rehabilitation patients 2 weeks–3 months post-stroke (not restricted to specific symptoms). n=60–100

Primary endpoint

Composite symptom burden (combined score of cognition [MoCA] + mood [HADS] + fatigue [FSS] + sleep [PSQI])

Secondary endpoints

FMA motor function, MBI, length of hospital stay, mRS at discharge

Design

Randomized controlled trial, spanning the entire inpatient rehabilitation period (typically 4–12 weeks)

Publication angle

The closest fit to real-world clinical practice, with the lowest enrollment and follow-up costs; symptom-cluster analysis is a current methodological trend in rehabilitation research.

Population

Post-stroke aphasia, currently receiving systematic speech therapy. n=30–50

Primary endpoint

WAB (Western Aphasia Battery) Aphasia Quotient (AQ)

Secondary endpoints

CADL communication ability, mood, family communication burden

Design

Randomized controlled trial, 12 weeks

Publication angle

Aphasia rehabilitation assessment is relatively time-consuming; it is recommended to assign this to centers with dedicated speech therapists.

Population

Stroke patients aged ≥65, MNA-SF indicating nutritional risk. n=40–60

Primary endpoint

MNA nutritional assessment + grip strength/skeletal muscle index

Secondary endpoints

Albumin/prealbumin, MBI, infectious complications, length of hospital stay

Design

Randomized controlled trial, 12 weeks

Publication angle

A cross-disciplinary nutrition-rehabilitation perspective, suitable for clinical nutrition journals; involves a different author group from rehabilitation medicine, so it can proceed in parallel.

Population

Mild-to-moderate TBI or 1–6 months post-craniotomy, clinically stable. n=30–50

Primary endpoint

MoCA + executive function

Secondary endpoints

Rivermead Post-Concussion Symptoms Questionnaire (RPQ), mood, sleep, fatigue, return-to-work rate

Design

Open-label pre-post comparison or randomized controlled trial, 12–24 weeks

Publication angle

Post-TBI syndrome has long lacked effective intervention options; either neurosurgery or rehabilitation medicine can lead this study.

Population

Women aged 40–58 in the perimenopausal or early postmenopausal period, modified Kupperman score ≥15, not using MHT. n=50–80

Primary endpoint

Modified Kupperman score or MRS (Menopause Rating Scale)

Secondary endpoints

Hot flash frequency and severity diary, PSQI, HADS, MENQOL quality of life

Design

Randomized controlled trial (control group receives lifestyle guidance), 12 weeks

Publication angle

Fast enrollment, low dropout rate, purely scale-based assessment — the lowest start-up cost direction in this catalog.

Population

Women with moderate-to-severe symptoms who have contraindications to MHT (e.g., history of thrombosis, liver disease, unexplained vaginal bleeding) or who explicitly refuse MHT. n=50–80

Primary endpoint

Modified Kupperman Index / MRS

Secondary endpoints

Hot flash diary, sleep, mood, quality of life, satisfaction with and willingness to continue the intervention

Design

Randomized controlled trial or single-arm pre-post comparison, 12 weeks

Publication angle

The population with the most clearly defined clinical gap—guidelines explicitly state that these patients lack effective alternatives; the "clinical need" section of the paper practically writes itself

Population

Women on guideline-concordant MHT for ≥3 months who still have residual symptoms (particularly mood, sleep, cognition). n=40–60

Primary endpoint

Severity of residual symptoms (Kupperman subscale items)

Secondary endpoints

Sleep, mood, cognition, MHT dose changes, MHT adherence

Design

Open-label pre-post comparison, 12 weeks

Publication angle

MHT is highly effective for vasomotor symptoms but has limited effect on mood and cognition—this "efficacy gap" is precisely the rationale for an add-on approach

Population

Perimenopausal women with mild-to-moderate scores on HADS or PHQ-9/GAD-7, not meeting diagnostic criteria for major depressive disorder. n=40–60

Primary endpoint

HADS or PHQ-9 + GAD-7

Secondary endpoints

Kupperman mood-related items, sleep, irritability, self-reported family and work relationships

Design

Randomized controlled trial, 12 weeks

Publication angle

Whether to use antidepressants for perimenopausal depression is a point of clinical controversy—there is clear room for non-pharmacological intervention in subclinical populations

Population

Perimenopausal women with PSQI >7 or ISI ≥15. n=40–60

Primary endpoint

PSQI / ISI

Secondary endpoints

Association analysis between nocturnal hot flashes and awakenings, sleep diary, daytime fatigue, mood, hypnotic medication use

Design

Randomized controlled trial, 8–12 weeks

Publication angle

Coupling analysis of nocturnal hot flashes and sleep disruption is an interesting angle—distinguishing "sleep improvement driven by hot-flash improvement" from "independent sleep improvement"

Population

Perimenopausal women aged 40–58 years reporting persistent fatigue for ≥3 months, FSS ≥4, with correctable causes such as anemia and thyroid dysfunction excluded. n=50–80

Primary endpoint

FSS (Fatigue Severity Scale) or MFI-20 (Multidimensional Fatigue Inventory)

Secondary endpoints

Kupperman/MRS, PSQI (distinguishing "fatigue due to poor sleep" from "independent fatigue"), HADS, MENQOL, WPAI work productivity

Design

Randomized controlled trial, 12 weeks

Publication angle

Fatigue consistently ranks among the top three perimenopausal complaints, yet is almost never studied as a primary endpoint—in the Kupperman scale it is just a single item. Isolating it as a standalone primary endpoint gives the study topic immediate distinctiveness; and the design requirement to exclude anemia/hypothyroidism actually lends the methodology greater rigor

Population

Perimenopausal women reporting "no motivation to do anything, loss of interest, daytime drowsiness," positive on AES or ESS, not meeting clinical diagnostic criteria for depression. n=40–60

Primary endpoint

AES (Apathy Evaluation Scale) + ESS (Epworth Sleepiness Scale)

Secondary endpoints

SHAPS anhedonia, HADS (as covariate adjustment), Kupperman, social activity participation, quality of life

Design

Open-label pre-post comparison or randomized controlled trial, 12 weeks

Publication angle

In clinical practice these complaints are often lumped together as "perimenopausal depression" and treated with antidepressants, yet most cases do not actually meet diagnostic criteria for depression. Separating "apathy" from "depression" is both an academic contribution and a direct answer to physicians' everyday dilemma of "whether to prescribe medication"

⚠️ Unified compliance baseline: In all oncology-direction protocols and publications, tumor response rate, progression-free survival, overall survival, or any other antitumor efficacy endpoints must not be included, and no antitumor-related claims may be made. Endpoints are strictly limited to symptom burden and quality of life. For safety, observations of interactions with antitumor therapy must be documented.

Population

Perimenopausal women with subjective memory/attention complaints and normal objective cognition. n=50–80

Primary endpoint

Subjective cognitive questionnaire (PDQ-5-D / Cognitive Failures Questionnaire, CFQ) + objective cognition (DSST, verbal fluency, working memory)

Secondary endpoints

Kupperman, mood, sleep, work productivity (WPAI)

Design

Randomized controlled trial, 12–24 weeks

Publication angle

"Menopausal brain fog" has been widely discussed internationally over the past two years but is almost entirely unstudied domestically, giving it the highest novelty; it is also theoretically supported by the estrogen-cognition hypothesis, making for a strong discussion section

Population

POI patients aged <40 years. n=30–50

Primary endpoint

MRS / MENQOL

Secondary endpoints

Mood, sleep, cognition, fertility-related psychological distress, social functioning

Design

Open-label pre-post comparison, 12–24 weeks

Publication angle

POI patients are young, carry a heavy psychological burden, and have excellent follow-up adherence—an overlooked, high-value population

Population

Breast or colorectal cancer patients currently receiving or having just completed anthracycline-, taxane-, or oxaliplatin-based chemotherapy, with cognitive complaints. n=50–80

Primary endpoint

FACT-Cog (subjective) + objective cognition (DSST, TMT-B, AVLT)

Secondary endpoints

HADS, ISI, FACIT-F fatigue, quality of life (EORTC QLQ-C30), return-to-work rate

Design

Randomized controlled trial, spanning the chemotherapy cycle plus 3-month follow-up after chemotherapy completion

Publication angle

CRCI is a leading topic in international oncology supportive care, with very limited domestic data; separating subjective from objective cognitive analysis is a standard bonus point in the discussion section

Population

Solid tumor patients with BFI (Brief Fatigue Inventory) ≥4 or FACIT-F indicating moderate-to-severe fatigue, with correctable causes such as anemia and hypothyroidism excluded. n=50–80

Primary endpoint

BFI or FACIT-F

Secondary endpoints

ECOG performance status, 6-minute walk test, sleep, mood, chemotherapy completion rate and dose intensity

Design

Randomized controlled trial, 8–12 weeks

Publication angle

CRF is the most prevalent symptom (60–90%) yet has no approved drug treatment; NCCN guidelines explicitly recommend non-pharmacological intervention—this is the single direction most closely aligned with Chienomoto's positioning. Setting "chemotherapy dose-intensity maintenance rate" as a secondary endpoint significantly enhances clinical relevance

Population

Solid tumor patients undergoing radical radiotherapy (breast, head and neck, or prostate cancer preferred), enrolled before radiotherapy begins. n=50–80

Primary endpoint

FACIT-F or BFI fatigue trajectory during radiotherapy and through 4 weeks after completion

Secondary endpoints

Peak fatigue and time of onset, number of radiotherapy interruptions/delays, ECOG, sleep, mood, QLQ-C30

Design

Randomized controlled trial, spanning the full radiotherapy course (typically 5–7 weeks) plus 4-week follow-up after completion

Publication angle

The time course of radiation-related fatigue is highly predictable (typically onset at weeks 2–3, peaking at the end of the course), which means the enrollment timing, observation window, and endpoint timing are all naturally fixed—making this the cleanest-designed, lowest-dropout direction among all fatigue studies; since patients come in for radiotherapy daily, follow-up costs are nearly zero

Population

Solid tumor patients during or after treatment, AES ≥34 or ESS ≥10, reporting "no desire to do anything, drowsy during the day," HADS depression subscale not meeting clinical diagnostic criteria. n=40–60

Primary endpoint

AES (Apathy Evaluation Scale) + ESS (Epworth Sleepiness Scale)

Secondary endpoints

FACIT-F fatigue (for differentiation from fatigue), HADS (as covariate adjustment), participation in daily activities, QLQ-C30, caregiver-observed ratings

Design

Open-label pre-post comparison, 12 weeks

Publication angle

In oncology supportive care, discussion almost always centers on fatigue; "apathy" as an independent construct is essentially unexplored. Yet clinically, patients who "just lie there and want to do nothing" are extremely common and are often mistakenly treated as depression. A three-way dissociation analysis of fatigue, apathy, and depression offers very high novelty

Population

Cancer patients during or after treatment, ISI ≥15. n=40–60

Primary endpoint

ISI (Insomnia Severity Index)

Secondary endpoints

PSQI, sleep diary, hypnotic medication dose, fatigue, mood, quality of life

Design

Randomized controlled trial, 8–12 weeks

Publication angle

Insomnia prevalence in cancer patients is roughly 2–3 times that of the general population, and long-term benzodiazepine use carries high risk; the angle of hypnotic dose reduction applies equally well here

Population

Solid tumor patients diagnosed ≤6 months ago, Distress Thermometer (DT) ≥4 or HADS ≥8. n=50–80

Primary endpoint

HADS anxiety and depression subscales

Secondary endpoints

DT (Distress Thermometer), sleep, fatigue, treatment adherence, QLQ-C30

Design

Randomized controlled trial, 12 weeks

Publication angle

Psycho-oncology is a distinct journal pool, with less competition than clinical oncology

Population

Post-surgical breast cancer patients receiving tamoxifen or an aromatase inhibitor for ≥3 months, with hot flashes, mood, sleep, or cognitive complaints. n=50–80

Primary endpoint

FACT-ES endocrine symptom subscale or Modified Kupperman Index

Secondary endpoints

Hot flash diary, HADS, ISI, FACT-Cog, joint pain VAS, endocrine therapy adherence and discontinuation rate

Design

Randomized controlled trial, 12–24 weeks

Publication angle

"Adherence" is the killer endpoint for this direction—the 5-year discontinuation rate for endocrine therapy is as high as 30–50%, driven mainly by these symptoms; linking symptom improvement to sustained adherence gives the clinical significance a direct tie to survival benefit

⚠️ Must be in place first

This direction involves hormone-sensitive tumors. Before enrollment, the company must provide assessment data on the phytoestrogen/estrogen-like activity of the formula's ingredients, and this must be clearly stated in the protocol and informed consent. If the data are insufficient, this direction should be deferred.

Population

Patients who are clinically stable after surgery for meningioma or glioma, or after whole-brain/local radiotherapy. n=30–50

Primary endpoint

MoCA + HVLT-R (Hopkins Verbal Learning Test–Revised; the standard instrument in radiotherapy cognition research)

Secondary endpoints

Executive function, fatigue, mood, seizure frequency, quality of life (QLQ-BN20)

Design

Randomized controlled trial or pre-post comparison, 24 weeks

Publication angle

Radiation-induced cognitive impairment is a well-defined clinical problem (memantine is currently the only drug with supporting evidence), leaving substantial room for research; neurosurgery and radiation oncology can jointly lead this direction

Population

Solid-tumor patients receiving PD-1/PD-L1 inhibitor therapy. n=40–60

Primary endpoint

FACIT-F fatigue

Secondary endpoints

QLQ-C30, sleep, mood, irAE documentation (safety)

Design

Open-label pre-post comparison, 12 weeks

Publication angle

Supportive-care research in immunotherapy populations is still in its infancy, offering high novelty

⚠️ Note

Immune-related adverse events must be clearly documented; the protocol must not include any language suggesting immunomodulatory effects

Population

Primary caregivers of patients with advanced or actively treated cancer, ZBI ≥21. n=40–60

Primary endpoint

ZBI (Zarit Burden Interview) caregiver burden

Secondary endpoints

Caregiver HADS, PSQI, quality of life, anticipatory grief (PG-12)

Design

Randomized controlled, 12 weeks

Publication angle

Oncology caregiver research has steady publication opportunities in nursing and psycho-oncology journals, and enrollment is very fast

Population

Patients requiring long-term nasogastric, nasoenteric, or gastrostomy tube feeding due to stroke, traumatic brain injury, hypoxic-ischemic encephalopathy, etc., clinically stable for ≥2 weeks. n=30–50

Primary endpoint

Composite feeding tolerability score (gastric residual volume, bloating, diarrhea, vomiting) + CRS-R (Coma Recovery Scale-Revised) or GCS

Secondary endpoints

Prealbumin, body weight, mid-upper arm circumference, incidence of pulmonary infection, participation in rehabilitation training, caregiver operational burden

Safety endpoints (key)

Aspiration events, tube occlusion, gastrointestinal adverse reactions — must be recorded case by case

Design

Open-label pre-post comparison or randomized controlled, 12 weeks

Publication angle

Suitability for nasogastric/tube administration is Chienomoto's unique advantage in this population — most functional foods cannot enter the tube-feeding pathway at all. Tube-fed patients are concentrated in neurology, post-ICU, and rehabilitation wards, so follow-up has essentially zero dropout; and "tube passability and tolerability" is itself a publishable paper on its own

※ Mandatory prerequisite: the company must first provide data on the product's solubility, viscosity, and tube passability (including occlusion risk across different tube diameters); without this, the project cannot be initiated. This is the direction with the strictest prerequisite in the entire catalog.

Population

Hospitalized patients ≥18 years, NRS-2002 ≥3 (nutritional risk present), FSS ≥4 or a clear complaint of fatigue, on top of standard nutritional support. n=50–80

Primary endpoint

FSS (Fatigue Severity Scale)

Secondary endpoints

PG-SGA (Patient-Generated Subjective Global Assessment), grip strength, albumin and prealbumin, daily oral intake, appetite score (SNAQ), length of hospital stay

Design

Randomized controlled (standard nutritional support ± Chienomoto), 8–12 weeks

Publication angle

Nutritional risk and fatigue are mutually causal, yet "fatigue" is rarely used as the primary endpoint in nutrition intervention studies. The nutrition department's assessment framework is already in place — every measure is data the department already collects routinely

Population

≥65 years old, meeting AWGS 2019 sarcopenia diagnostic criteria, or FRAIL scale score 1–3 (pre-frail to frail). n=50–80

Primary endpoint

Grip strength + 4-meter gait speed (or SPPB, Short Physical Performance Battery)

Secondary endpoints

Skeletal muscle mass index (bioelectrical impedance), FSS fatigue, MNA-SF, falls and hospitalization events, cognition and mood

Design

Randomized controlled (control group: resistance exercise + nutrition education), 24 weeks

Publication angle

Sarcopenia and frailty are currently the leading topic in geriatric medicine, and fatigue is one of the five core criteria of the Fried frailty phenotype. The nutrition department, geriatrics, and rehabilitation medicine can each lead this study, and it can be submitted to either clinical nutrition or geriatric medicine journals

This shares the same population as A11 in the dementia domain but takes a different angle — the two can be led separately by the nutrition department and geriatrics while sharing the same subject pool.

Population

Patients ≥65 years undergoing elective major surgery or hip fracture surgery, with preoperative MNA-SF indicating nutritional risk or malnutrition. n=60–100

Primary endpoint

Incidence of postoperative delirium (CAM or 3D-CAM, assessed daily on postoperative days 1–7)

Secondary endpoints

Postoperative cognition (MoCA at discharge and at 3 months postoperatively), grip strength, length of hospital stay, complication rate, 30-day readmission rate

Design

Randomized controlled, from 7 days preoperatively to 30 days postoperatively

Publication angle

Postoperative delirium occurs in as many as 20–40% of older hip fracture patients, preventive measures remain limited, and it is a hard outcome of shared concern to anesthesiology, geriatrics, and orthopedics. Nutritional intervention for delirium prevention is a current international hotspot, and delirium's presentation (fluctuating consciousness, agitation, hallucinations) aligns closely with No. 4's intended scope

This direction's endpoint is a hard outcome with major clinical significance, but it requires daily postoperative assessment — recommended for centers with a geriatric hip-fracture fast-track pathway or an ERAS team.

Population

≥65 years old, MNA-SF ≤11 (malnourished or at nutritional risk) and MoCA <26. n=50–80

Primary endpoint

Dual endpoints: MoCA and MNA-SF

Secondary endpoints

AVLT (Auditory Verbal Learning Test), grip strength, body weight and composition, activities of daily living (IADL), mood, eating behavior

Design

Randomized controlled, 24 weeks

Publication angle

The "nutrition-cognition axis" is a hot cross-disciplinary topic between geriatric medicine and clinical nutrition: malnutrition is both a consequence and a risk factor for dementia, yet intervention studies addressing this bidirectional relationship are very scarce domestically

Population

Post-stroke dysphagia (Kubota Water Swallowing Test grade ≥3, or confirmed by VFSS/FEES), with restricted oral intake or requiring tube feeding. n=40–60

Primary endpoint

Nutritional status (MNA-SF, body weight, prealbumin) + FOIS (Functional Oral Intake Scale)

Secondary endpoints

Incidence of pulmonary infection, NIHSS, MBI (Modified Barthel Index) activities of daily living, time to tube removal, length of hospital stay

Design

Randomized controlled, 12 weeks

Publication angle

Dysphagia is the leading cause of post-stroke malnutrition and aspiration pneumonia, making nutrition and rehabilitation departments natural collaborators. Because the product can be administered via feeding tube, patients with restricted oral intake can be covered throughout the study without dropping out due to a change in administration route

Population

Solid-tumor patients, PG-SGA ≥4 (moderate-to-severe malnutrition) and BFI ≥4. n=40–60

Primary endpoint

PG-SGA score + BFI (Brief Fatigue Inventory)

Secondary endpoints

Body weight and fat-free mass, grip strength, chemotherapy completion rate and dose intensity, EORTC QLQ-C30, ECOG performance status

Design

Randomized controlled (standard nutritional support ± Chienomoto), 12 weeks

Publication angle

Malnutrition and cancer-related fatigue are the two main threads of oncology supportive care, yet they are usually studied separately. Bringing both into a single endpoint framework allows joint authorship between the nutrition department and oncology

This addresses the same clinical question as O2 in the oncology domain but with a different lead department — recommended to choose one or the other to avoid topic overlap within the same center.

Population

Children aged 3–8 with pronounced picky/selective eating behavior, height or weight below the 10th percentile for age and sex, with organic disease excluded. n=40–60

Primary endpoint

Change in weight and height Z-scores at 24 weeks

Secondary endpoints

CEBQ (Children's Eating Behaviour Questionnaire), daily energy and protein intake, serum zinc and ferritin, sleep, mood, parental feeding stress

Design

Randomized controlled (control group: feeding behavior guidance), 24 weeks

Publication angle

Picky/selective eating is one of the most frequent complaints in pediatric health-care and children's nutrition clinics; parental anxiety is very high and follow-up adherence is excellent. Both pediatric health care and nutrition departments can lead this study, and it is the fastest-enrolling direction in this domain

Population

Regular hemodialysis for ≥3 months, FSS ≥4 or a significant decline in the SF-36 vitality domain. n=40–60

Primary endpoint

FSS (Fatigue Severity Scale)

Secondary endpoints

Post-dialysis recovery time, grip strength, nutritional markers (albumin, nPCR), KDQOL quality of life, depression and sleep

Safety endpoints (key)

Changes in serum potassium, phosphorus, creatinine, and BUN; dialysis adequacy (Kt/V) — must be monitored before and after every dialysis session

Design

Open-label pre-post comparison, 12 weeks

Publication angle

Dialysis-related fatigue has an incidence exceeding 60% and is the symptom patients care about most yet is least often targeted by intervention. Conducted jointly by nephrology and the nutrition department, with a fixed population and a naturally built-in follow-up rhythm (three hospital visits per week) and an extremely low dropout rate

※ Mandatory prerequisite: in populations with renal insufficiency, the electrolyte and metabolic load of any supplement must be strictly monitored. This direction may only be initiated after obtaining test data on the product's potassium, phosphorus, and sodium content; if this data is insufficient, the project should be postponed.