TAP-GRIN: L‑serine for GRIN-related neurodevelopmental disorders
L-serine Supplementation in Patients With GRIN-related Neurodevelopmental Disorders: Multicentre Protocol for an Aggregated Series of Randomised, Placebo-controlled N-of-1 Trials
This trial will test whether oral L‑serine helps children and young adults (ages 2–30) who have GRIN-related neurodevelopmental disorders caused by loss-of-function variants.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 2 Years to 30 Years |
| Sex | All |
| Sponsor | Meyer Children's Hospital IRCCS Academic / other |
| Locations | 3 sites (Lyon and 2 other locations) |
| Trial ID | NCT07377032 on ClinicalTrials.gov |
What this trial studies
This is a randomized, double-blind, placebo-controlled series of aggregated n-of-1 trials testing oral L‑serine versus placebo in participants aged 2–30 with pathogenic or likely pathogenic loss-of-function variants in GRIN1, GRIN2A, GRIN2B, or GRIN2D. The primary clinical outcome is change in overall status measured by the Clinical Global Impression‑Severity (CGI‑S) score, with secondary outcomes including behavior, cognition, adaptive and motor function, sleep, seizure frequency and EEG findings. The trial also monitors safety and tolerability and will explore neurophysiological biomarkers such as TMS‑EMG and TMS‑EEG for treatment response. Each participant serves as their own control through alternating treatment and placebo periods, allowing within-person comparisons despite the rarity and heterogeneity of the condition.
Who should consider this trial
Good fit: Ideal candidates are children and young adults (2–30 years) with a confirmed pathogenic or likely pathogenic loss-of-function variant in GRIN1, GRIN2A, GRIN2B, or GRIN2D whose caregivers can provide consent and comply with study procedures.
Not a fit: Patients without loss-of-function GRIN variants (for example those with gain-of-function changes), children under age 2, or those unable to comply with study procedures are unlikely to benefit from this intervention in the trial context.
Why it matters
Potential benefit: If effective, L‑serine supplementation could improve overall clinical functioning including behavior, cognition, motor skills and possibly reduce seizures in patients with LoF GRIN variants.
How similar studies have performed: Small case series and early-phase studies have reported clinical improvements with L‑serine in individuals with LoF GRIN variants, but randomized, blinded evidence has been limited until now.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Clinical diagnosis of a GRIN-related neurodevelopmental disorder (GRIN-NDD) * Presence of a pathogenic or likely pathogenic loss-of-function (LoF) variant in GRIN1, GRIN2A, GRIN2B, or GRIN2D * Parent(s), caregiver(s), or legally authorised representative(s) have been informed of the nature of the study and have provided written informed consent. * Participants who are able to do so have provided written informed consent or assent, according to local regulations and cognitive capacity. * Parent(s)/caregiver(s) are willing and able to comply with study procedures and visits, in the opinion of the investigator. * Participants who have previously received L-serine supplementation are willing to discontinue L-serine for at least one week prior to the baseline observation period. Exclusion Criteria: * Age younger than 2 years at screening. * Known hypersensitivity or intolerance to L-serine, placebo, or any excipients used in the study formulations. * Presence of a clinically significant unstable medical condition (other than epilepsy) that, in the investigator's judgement, may place the participant at increased risk or interfere with study participation. * Any other significant disease or disorder that may compromise participant safety, affect study outcomes, or impair the participant's ability to complete the study procedures. * Inadequate supervision by parent(s) or caregiver(s), as judged by the investigator. * Participation in another clinical trial involving an investigational medicinal product within the previous 6 months. * Female participants who are pregnant or breastfeeding. * Presence of a GRIN1, GRIN2A, GRIN2B, or GRIN2D variant for which a clear loss-of-function effect cannot be demonstrated.
Where this trial is running
Lyon and 2 other locations
- Hospices Civils de Lyon — Lyon, France (Not_yet_recruiting)
- Meyer Children's Hospital — Florence, Italy (Recruiting)
- Children's Memorial Health Institute — Warsaw, Poland (Recruiting)
Study contacts
- Study coordinator: Simona Balestrini, Md, PhD
- Email: simona.balestrini@meyer.it
- Phone: 00390555662719
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.