Clinical trial NCT04948138: Glutamine Supplement in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) Syndrome
Official title: Glutamine Supplement in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) Syndrome in Order to Prevent Neurological Damage.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: MELAS Syndrome
Keywords: MELAS
Glutamine
Oral supplements
Lactate
Cerebrospinal fluid
Magnetic resonance spectroscopy
Lead sponsor: Hospital Universitario 12 de Octubre
Sponsor class: OTHER
First posted: 2021-07-01
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Glutamine oral supplementation
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Amino Acids concentration in cerebrospinal fluid
timeFrame: 3 months
measure: Lactate concentration in cerebrospinal fluid
timeFrame: 3 months
Secondary outcomes:
measure: Lactate measured by magnetic resonance spectroscopy.
timeFrame: 3 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Hospital Universitario 12 de Octubre
name: Jesús González de la Aleja Tejera, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. 2023 Feb;30(2):538-547. doi: 10.1111/ene.15626. Epub 2022 Nov 18.