Clinical Long Term Evaluation of Glutamine Supplement in MELAS Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to assesses the clinical efficacy of oral supplementation with glutamine over 3 years.

Detailed Description
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Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder. The most common mutation is in the mtDNA gene MT-TL1 encoding the mitochondrial tRNALeu (UUR). For understanding the development of seizures in patients with mitochondrial disease, a study has recently emphasized the deficiency of astrocytic glutamine synthetase, creating a disinhibited neuronal network for seizure generation. The investigators propose to evaluate nine patients with mitochondrial DNA mutation and MELAS. Patients will receive oral supplementation with 12-18 g/day of glutamine (adjusted for weight and plasma concentrations). The primary outcome measures modification in clinical scales.

Official Title
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Clinical Long Term Evaluation of Glutamine Supplement in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) Syndrome in Order to Prevent Neurological Damage.

Conditions
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MELAS Syndrome

Intervention / Treatment
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* Dietary Supplement: Glutamine oral supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MELAS syndrome Clinically and genetically confirmed. Patients have already participated in GLN-9-MIT study Exclusion Criteria: subjects harboring a MELAS-related pathogenic mtDNA mutation no fulfilling the complete diagnostic criteria for the MELAS phenotype

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Glutamine oral supplementation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MELAS<br>Patients with MELAS syndrome will receive 12-18g/day of glutamine | Dietary Supplement: Glutamine oral supplement<br>* 12-18 g /day of glutamine supplementation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy; JMDRS | Change from Baseline clinical scale (Japanese mitochondrial disease rating scale (JMDRS)) at 12,24,36 months to test Clinical efficacy of oral supplementation | 36 months | 
| Clinical efficacy; MMSE | Change from Baseline cognitive test (Mini-Mental State Examination (MMSE)) at 12,24,36 months to test Clinical efficacy of oral supplementation | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | To recorde all adverse events grades; with special interest on investigations (CTCAE v5.0, 2017) | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MELAS, Glutamine, Amino acids, Oral supplements