Clinical Research Directory

TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders

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.

Honeycomb: Evaluation of Radiprodil in Children with GRIN-related Disorder

Study RAD-GRIN-101 is a phase 1B trial to assess safety, tolerability, PK, and potential efficacy of radiprodil for the treatment of GRIN-related disorder in children with a Gain-of-Function (GoF) genetic variant. The study is open-label, so all participants will be treated with radiprodil. Subjects' participation in the study is expected to last up to six months in Part A. After the end of part A, all participants who are still eligible can choose to continue to receive radiprodil as part of an open-label long-term treatment period (Part B).