Assess the potential efficay of L-serine dietary supplementation in patients children with a GRIN2B LoS mutation.
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PRPP (Perceive-Recall-Plan-Perform) assessment
Secondary outcome
• Goal Attainment Scaling (GAS)
• If epilepsy: seizure control (seizure log book)
• EEG
• Sleep (sleep log book)
• Irritability (Brief Irritability Test)
• Bowel movement assessment (Bristol stool scale)
• Language (MacArthur)
• Quality of Life (PedsQL)
Background summary
Loss-of-function (LoF) mutations in GRIN2B result in neurologic abnormalities
due to N-methyl-D-aspartate receptor (NMDAR) dysfunction. In vitro experiments
showed that the naturally occurring coagonist D-serine restores function to
GluN2B (mutation)-containing NMDARs. In a 5 years old patient with a missense
mutation in GRIN2B with a Rett-like syndrome with severe encephalopathy notable
improvements in motor and cognitive performance and communication were observed
after L-serine dietary supplementation. Thus, L-serine supplementation, which
has proven safe and well-tolerated in patients with inborn errors of serine
biosynthesis, offers a therapeutic strategy for patients with GRIN2B
deficiency, previously considered untreatable and for which there exist no
other options.
Study objective
Assess the potential efficay of L-serine dietary supplementation in patients
children with a GRIN2B LoS mutation.
Study design
A series of prospective double-blind randomized and placebo-controlled multiple
cross-over, single centre studies within a participant (multiple n-of-1
trials).
Intervention
Each patient receives multiple blocks consisting of 4 time daily L-serine (500
mg/kg/day) alternated with placebo and washout periods.
Study burden and risks
No treatment is available for this severely affected patient group. There is an
unmet medical need to treat this severe encephalopathy and other neurological
conditions. L-serine is a semi-essential amino acid that is found in normal
diet and is naturally synthesized by humans. L-serine intake has shown no
adverse events to date. A recent study demonstrated that L-serine
supplementation might ameliorate motor and cognitive performance in
GRIN2B-related encephalopathy. Because of the major impact on quality of life,
early innervation is necessary. Therefore paediatric patients with GRIN2B
deficiency are necessary to include. Risk for subject participating in this
trial consist of additional blood draw. As the clinical trial enables a
potential treatment for patients that lack treatment options, we will expect
that the benefits substantially outweigh the burden of participation.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1) The patient or the parent(s)/legal guardian(s) must provide written informed
consent before start of the study;
2) Male and female patients with confirmed GRIN2B LoF mutation;
3) >=37 weeks, <=18 years
4) Able to travel to the study site.
Exclusion criteria
1) Has taken L-serine supplement within 30 days prior to enrolment;
2) The patient has received another investigational product within 30 days
prior to enrolment;
3) Known hypersensitivity reactions, intolerance or adverse reactions to
L-serine or the inactive ingredients;
4) The patient is unwilling or, in the investigator*s opinion, unable to adhere
to the requirements of the study;
5) The patient is unable to swallow powder and has no other enteral access
(e.g. gastrostomy);
6) Any condition or abnormality which may, in the opinion of the investigator,
compromise the safety of patients.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-000241-32-NL |
| CCMO | NL80290.018.22 |