Glutamine Supplement in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to assesses the efficacy of oral supplementation with glutamine over three months on several amino acids and lactate concentration measured in cerebrospinal fluid and cerebral lactate measured by magnetic resonance spectroscopy.

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 10-15 g/day of glutamine (adjusted for weight and plasma concentrations). The primary outcome measures several amino acids (including glutamine) and lactate concentration measured in cerebrospinal fluid and cerebral lactate measured by magnetic resonance spectroscopy.

Official Title
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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 supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of MELAS syndrome is based on medical history (lactic acidosis, stroke-like episodes, and encephalomyopathy). Subjects have to be clinically stable for more than six months after any stroke-like episodes. All subjects have to be genetically confirmed. 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 (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) syndrome<br>Patients with MELAS syndrome that will receive oral supplementation with 10-15 g/day of glutamine (adjusted for weight and plasma concentrations) | Dietary Supplement: Glutamine oral supplementation<br>* Oral supplementation with 10-15 g/day of glutamine (adjusted for weight and plasma concentrations).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amino Acids concentration in cerebrospinal fluid | Amino Acids (including glutamine) concentration measured in cerebrospinal fluid | 3 months | 
| Lactate concentration in cerebrospinal fluid | Lactate concentration measured in cerebrospinal fluid | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate measured by magnetic resonance spectroscopy. | Cerebral Lactate measured by magnetic resonance spectroscopy. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glutamine, Oral supplements, Lactate, MELAS, Cerebrospinal fluid, Magnetic resonance spectroscopy