Nitric Oxide Production in MELAS Syndrome

Arginine Flux and Nitric Oxide Production in Patients With MELAS Syndrome and the Effect of Arginine and Citrulline Supplementation

Introduction

Baylor College of Medicine and Texas Children's Hospital are recruiting individuals with MELAS syndrome for a clinical study. MELAS syndrome is a mitochondrial disease; patients with this disease have muscle weakness and often develop brain strokes, where blood does not flow normally to different parts of the brain. It is believed that these strokes could be due to decreased production of nitric oxide, a naturally occurring compound important for normal blood vessel function. Nitric oxide is made from arginine and citrulline that are normally found in our bodies.

What is the purpose of this study? The purpose of this study is to measure nitric oxide in individuals with MELAS and see if giving arginine or citrulline will increase the formation of nitric oxide. Nitric oxide is thought to be helpful in preventing strokes. Therefore, if arginine and/or citrulline are shown to increase the formation of nitric oxide, they could be used to prevent or treat the strokes in patients with MELAS syndrome.

Study Overview

• Status: Completed
• Conditions: MELAS Syndrome
• Intervention / Treatment: Dietary supplement: Arginine and citrulline supplementations

Detailed Description

What does the study involve? Individuals with MELAS syndrome will be admitted twice to the General Clinical Research Center (GCRC) at Texas Children's Hospital. Each time they will stay for five days, during which a special diet will be provided. Nitric oxide production will be measured by stable isotopes infusion technique that involves placing small tubes in veins (IV catheter), blood sampling, and injecting a harmless stable isotope. Stable isotopes are forms of normal compounds that can be measured accurately. They are not radioactive and there are no known risks to giving them; they are already part of your body in small amounts.

During the first admission nitric oxide levels will be measured, then arginine supplementation will be provided for 48 hours, after which nitric oxide levels will be re-measured to determine the effect of arginine supplementation. During the second admission, the effect of citrulline supplementation will be measured.

Who can participate in the study? Adults or children affected with MELAS syndrome and carrying the DNA change that causes the condition (3243 A>G mutation) can participate. Adults without MELAS disease will be recruited to participate as control subjects.

How to get more information? Subjects interested in participation or getting more information can contact Dr. Ayman El-Hattab at email: elhattab@bcm.edu, office phone: 832-822-4289, cell phone: 646-660-5666, or pager: 832-824-7243 (5523).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age from 3 - 65 years
2. Clinical diagnosis of MELAS syndrome
3. Carrying the m.3243A>G mutation

Exclusion Criteria:

1. Having acute or chronic disease or physical disability that will interfere with the ability to undergo the study procedures
2. Being pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: arginine supplementation; Oral L-arginine supplementation will be administered to subjects with MELAS for 48 hours at a dose of 10 grams per M2 per day. Arginine will be given every 4 hours.	Dietary supplement: Arginine and citrulline supplementations; Arginine or citrulline will be given orally at dose of 10 grams per meter square body surface area per day divided every 4 hours.
Active Comparator: citrulline supplementation; Oral L-citrulline supplementation will be administered to subjects with MELAS for 48 hours at a dose of 10 grams per M2 per day. Citrulline will be given every 4 hours	Dietary supplement: Arginine and citrulline supplementations; Arginine or citrulline will be given orally at dose of 10 grams per meter square body surface area per day divided every 4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in nitric oxide production	Nitric oxide production will be measured at baseline before supplementation and after 48 hours of arginine or citrulline supplementation

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Fernando Scaglia, M.D., Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: April 19, 2011
• First Submitted That Met QC Criteria: April 19, 2011
• First Posted (Estimate): April 20, 2011

Study Record Updates

• Last Update Posted (Estimate): April 5, 2016
• Last Update Submitted That Met QC Criteria: April 1, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; 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; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Syndrome; MELAS Syndrome
• Other Study ID Numbers: H-24783

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Yes the data have been made available to