TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
Recruiting · NCT07377032 · Interventional (participants receive a specific treatment) · Lead sponsor: Meyer Children's Hospital IRCCS
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
The goal of this clinical study is to find out whether L-serine dietary supplementation helps improve overall clinical functioning in children and young adults (2-30 years) with GRIN-related neurodevelopmental disorders (GRIN-NDD) caused by loss-of-function (LoF) variants in GRIN1, GRIN2A, GRIN2B, or GRIN2D. It will also assess the safety and tolerability of L-serine. The main questions it aims to answer are: Does L-serine improve overall clinical status, measured mainly by the Clinical Global Impression-Severity (CGI-S) score? Does L-serine improve behaviour, cognition, adaptive functioning, motor skills, sleep, and (in those with epilepsy) seizure frequency and EEG findings? What side effects or medical problems occur during L-serine compared with placebo? Do neurophysiological measures (including TMS-EMG/TMS-EEG) change with treatment and potentially act as biomarkers of response? Researchers will compare L-serine to a placebo (maltodextrin powder with similar appearance/texture) using a randomised, double-blind, placebo-controlled "n-of-1" approach, where each participant receives both treatments in alternating periods. Results from multiple single-patient trials will then be combined (aggregated) to estimate the overall treatment effect across the study population. Participants will: Complete a 4-week baseline period with assessments (and seizure diary use where applicable) Receive L-serine and placebo in alternating 3-month periods within each cycle (minimum 2 cycles, up to 4 cycles; each cycle lasts 6 months) Take the assigned study product by mouth 3 times per day at 500 mg/kg/day (maximum 30 g/day for participants ≥60 kg) Have the first 7 days of each 3-month period treated as washout, with data from that week not analysed Attend regular clinic visits for clinical exams, safety labs, and standardized assessments of global status, behaviour/cognition, motor function, and sleep If they have epilepsy: keep a seizure diary and undergo EEG assessments after each treatment period In some sites (Italy and France): undergo TMS-based neurophysiology testing Optionally, a subset may join a cellular biomarker substudy (blood collection to generate iPSC-derived neuronal models and organoids) to explore treatment effects in variant-specific lab models.
Who can take part
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 it is running
3 locations listed.
- Meyer Children's Hospital - Florence, Italy
- Hospices Civils de Lyon - Lyon, France
- Children's Memorial Health Institute - Warsaw, Poland