L-Citrulline Dose Finding Safety Study in MELAS
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|ClinicalTrials.gov Identifier: NCT03952234|
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : April 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|MELAS Syndrome||Drug: L-Citrulline||Phase 1|
The human body is made of many cells and each cell contains many mitochondria. Mitochondria are called the powerhouses of the cell, because they produce the energy needed for a cell to be healthy and function the way it is meant to.
Diseases of the mitochondria affect the way the tissues and cells of the body make and use energy, and can affect almost all the different organs of the body like the brain and the muscles.
MELAS syndrome is one of the mitochondrial diseases; patients with this disease have different complications including stroke like episodes, headache, muscle weakness, fatigue, and hearing loss. One of the factors contributing to complications seen in patients with MELAS syndrome, in particular the stroke like episodes, is decreased amount of an element called nitric oxide. This element is made in the bodies from an amino acid called arginine. Amino acids are the building blocks of proteins. Proteins make the muscles in the bodies, and they are present in meat, chicken and fish.
In this study, the highest acceptable dose of an amino acid called citrulline will be established in participants who have a mitochondrial disorder. Previous research conducted by several groups including Baylor College of Medicine has determined that there is a deficiency of a compound called nitric oxide in patients affected with MELAS.
The lack of nitric oxide could cause constriction of blood vessels in the brain making it easier for these patients to have a metabolic stroke. The amino acid citrulline is a foundation for nitric oxide. In earlier studies, the investigator has found that there is more production of nitric oxide in the body when participants affected with MELAS take L-citrulline.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||L-Citrulline|
|Masking:||None (Open Label)|
|Official Title:||Phase-1, Dose Finding and Safety Study on L- Citrulline Treatment of Nitric Oxide Deficiency in MELAS|
|Actual Study Start Date :||April 22, 2021|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||April 2023|
Dose finding safety study
In this study, the highest acceptable dose of an amino acid called citrulline will be established in people who have a mitochondrial disorder. Previous research conducted by several groups including our center at Baylor College of Medicine has determined that there is a deficiency of a compound called nitric oxide in people affected with MELAS.
To determine the safest maximum dose of L-Citrulline which could be used as a potential treatment for adults with disorder of energy metabolism called MELAS
Other Name: L-Citrulline powder
- Establishment of the maximum tolerable dose of L-citrulline in patients with MELAS syndrome by measuring the incidence of dose limiting toxicities (DLTs) [ Time Frame: Eight weeks ]
Measurement of the incidence of treatment-emergent adverse events in a safety and tolerability phase 1 study.
The following Dose Limiting
Toxicities (DLTs) will be measured:
Treatment-related adverse events (AE) at grade 3 or higher, or worsening of baseline status, defined by increase of at least 2 grades, if baseline grade is ≤1. The AEs will be graded based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Subjects will be specifically monitored for the occurrence of the following adverse events:
- Blurred Vision
- Concentration Impairment
- Orthostatic hypotension defined as a decrease in systolic blood pressure of 20 mm Hg, or a decrease in diastolic blood pressure of 10 mm Hg, within three minutes of standing when compared with blood pressure from the sitting or supine position.
- Changes in cerebral blood flow effected by the use of citrulline supplementation [ Time Frame: Four weeks ]Changes in cerebral blood flow by using arterial spin-labeling (ASL) magnetic resonance imaging (MRI) will be measured in milliliters per 100 grams of tissue per minute at four weeks while on citrulline and compared to measurement at baseline in milliliters per 100 grams of tissue per minute before the use of citrulline
- Changes in cerebrovascular reactivity effected by the use of citrulline supplementation [ Time Frame: Four weeks ]Changes in cerebrovascular reactivity by using arterial spin-labeling (ASL) magnetic resonance imaging (MRI) will be measured in milliliters per 100 grams of tissue per minute at four weeks while on citrulline and compared to measurement in milliliters per 100 grams of tissue per minute at baseline before use of citrulline
- Changes effected by the use of citrulline supplementation in the micromolar concentration of plasma amino acids citrulline, arginine, ornithine, and alanine levels. [ Time Frame: Four weeks ]Concentrations of plasma citrulline, arginine, ornithine, and alanine will be measured at baseline before citrulline supplementation and at four weeks during citrulline supplementation to determine the changes in concentration in micromoles per liter
- Changes effected by the use of citrulline in the micromolar concentration of plasma alanine and in the concentration of plasma lactate (expressed in millimole per liter) [ Time Frame: Four weeks ]Concentrations of plasma lactate and plasma alanine will be measured at baseline before citrulline supplementation and at four weeks during citrulline supplementation to determine the change in concentration in micromoles per liter in plasma alanine and in millimoles per liter in plasma lactate
- Changes effected by the use of citrulline in the concentration of plasma guanidino compounds [ Time Frame: One week ]Concentration of plasma guanidino compounds will be measured at baseline before citrulline supplementation and at one week during citrulline supplementation by using untargeted metabolomics profiling and values will be expressed in Z scores
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03952234
|Contact: MAY ALI||+1 email@example.com|
|Contact: DIANNE BAURI, N.P.||+1 firstname.lastname@example.org|
|United States, Texas|
|Baylor St. Luke'S Medical Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: FERNANDO SCAGLIA, M.D. 832-822-4280 email@example.com|
|Contact: Claudia soler, M.D. +1 832-822-4280 firstname.lastname@example.org|
|Principal Investigator: FERNANDO SCAGLIA, M.D.|
|Sub-Investigator: CLAUDIA SOLER, M.D.|
|Sub-Investigator: STEPHEN KRALIK, M.D.|
|Sub-Investigator: DIANNE BAURI, N.P.|
|Sub-Investigator: SAIMA ALI, N.P|
|Principal Investigator:||FERNANDO SCAGLIA, M.D||Baylor College of Medicine|