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

Glutamine Supplement in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) Syndrome in Order to Prevent Neurological Damage.

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.

Study Overview

• Status: Completed
• Conditions: MELAS Syndrome
• Intervention / Treatment: Dietary supplement: Glutamine oral supplementation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) syndrome; 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; Oral supplementation with 10-15 g/day of glutamine (adjusted for weight and plasma concentrations).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jesús González de la Aleja Tejera
• Investigators: Principal Investigator: Jesús González de la Aleja Tejera, MD, PhD, Hospital Universitario 12 de Octubre

Publications and helpful links

General Publications

• Guerrero-Molina MP, Morales-Conejo M, Delmiro A, Moran M, Dominguez-Gonzalez C, Arranz-Canales E, Ramos-Gonzalez A, Arenas J, Martin MA, de la Aleja JG. High-dose oral glutamine supplementation reduces elevated glutamate levels in cerebrospinal fluid in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome. Eur J Neurol. 2022 Nov 5. doi: 10.1111/ene.15626. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Actual): September 9, 2021
• Study Completion (Actual): October 6, 2021

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 8, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: MELAS; Cerebrospinal fluid; Glutamine; Magnetic resonance spectroscopy; Lactate; Oral supplements
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Mitochondrial Diseases; Brain Diseases, Metabolic, Inborn; Cerebral Small Vessel Diseases; Acid-Base Imbalance; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Syndrome; Brain Diseases; MELAS Syndrome; Acidosis; Acidosis, Lactic
• Other Study ID Numbers: GLN-9-MIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No