Nitric Oxide Production in MELAS Syndrome

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ClinicalTrials.gov Identifier: NCT01339494

Recruitment Status : Completed

First Posted : April 20, 2011

Last Update Posted : April 5, 2016

Sponsor:

Information provided by (Responsible Party):

Fernando Scaglia, Baylor College of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
MELAS Syndrome	Dietary Supplement: Arginine and citrulline supplementations	Early Phase 1

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 Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	30 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Arginine Flux and Nitric Oxide Production in Patients With MELAS Syndrome and the Effect of Arginine and Citrulline Supplementation
Study Start Date :	July 2009
Actual Primary Completion Date :	April 2016
Actual Study Completion Date :	April 2016

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

Drug Information available for: Arginine Arginine Hydrochloride Nitric oxide

Genetic and Rare Diseases Information Center resources: Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like Episodes Encephalomyopathy

U.S. FDA Resources

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	3 Years to 65 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

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): NCT01339494

Locations


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

Sponsors and Collaborators

Baylor College of Medicine

Investigators


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

More Information


Responsible Party:	Fernando Scaglia, Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT01339494 History of Changes
Other Study ID Numbers:	H-24783
First Posted:	April 20, 2011 Key Record Dates
Last Update Posted:	April 5, 2016
Last Verified:	April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Yes the data have been made available to

Additional relevant MeSH terms:


Mitochondrial Encephalomyopathies Mitochondrial Myopathies Muscular Diseases Mitochondrial Diseases Syndrome MELAS Syndrome Disease Pathologic Processes Musculoskeletal Diseases Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Cerebral Small Vessel Diseases	Cerebrovascular Disorders Neuromuscular Diseases Vascular Diseases Cardiovascular Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Nitric Oxide Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Free Radical Scavengers

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