L-arginine Therapy on Endothelium-dependent Vasodilation & Mitochondrial Metabolism in MELAS Syndrome

NCT01603446 | Completed Phase 2

• 1 other identifier: 1000023405
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

MELAS patients suffer from exercise intolerance, weakness, poor vision or blindness, poor growth, developmental delay, and deafness. They also have unique 'stroke-like' episodes (SLEs) which are not due to blockages of large or medium arteries. These 'strokes' are thought to be due to energy failure of very small brain blood vessels combined with energy failure in the mitochondria (cell battery) of the brain cells, especially in the back region of the brain in the vision centre. This leads to visual loss and paralysis. The overall goal of this study is to better understand the mechanism of these SLEs at the level of the brain cells and small blood vessels.

Conditions

MELAS Syndrome

Keywords

pediatric; MELAS; mechanism of action of L-arginine

Outcome Measures

Primary Outcomes (1)

• Muscle function investigation via 31P-Magnetic resonance spectroscopy

  We will study exercising quadriceps using our MR-compatible up-down ergometer and our well established aerobic exercise protocol at 65 % of maximal voluntary contraction.

  60 to 105 minutes post dose

Secondary Outcomes (3)

• Total body maximal aerobic capacity

  60-75 mins post dose

• CerebroVascular Reactivity

  75-105 mins post dose

• Exhaled Nitric Oxide (eNO)

  75 mins pre dose, 75 mins post dose

Study Arms (2)

MELAS Patients

EXPERIMENTAL

Three siblings with MELAS (A3243G) syndrome (1 male; 2 females) aged 17-23 years, followed or previously followed in the Neurometabolic Clinic at the Hospital for Sick Children will be studied.

Drug: L-Arginine

Control Group

NO INTERVENTION

Four age- and sex-matched controls and female controls will be matched according to phase in menstrual cycle corresponding with their age-matched MELAS subjects

Interventions

L-Arginine DRUG

NOW® L-Arginine powder

MELAS Patients

Eligibility Criteria

• Age: 17 Years - 23 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Experimental Siblings with MELAS (A3243G) syndrome
• years
• Followed Neurometabolic Clinic at the Hospital for Sick Children will be studied.
• Normal electrolytes, glucose, renal and liver functions \& no history of gastrointestinal, respiratory or cardiac problems.
• Controls
• Aged 17-23- Sex matched to the MELAS subjects

You may not qualify if:

• Controls
• Experience migraines
• Have a metabolic disorder
• Taking medications predisposing to lactic acidosis or vasodilatation
• Neuromuscular/neurologic condition
• Cardiac or pulmonary disease
• Visual abnormalities
• Hypertension, anemia and prothrombotic state. Control subjects
• Contraindication for MRI (pacemaker, ocular metal, claustrophobia, tattoos) will be excluded from the study.

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5V1X8, Canada

Location

Related Publications (2)

• Rodan LH, Poublanc J, Fisher JA, Sobczyk O, Mikulis DJ, Tein I. L-arginine effects on cerebrovascular reactivity, perfusion and neurovascular coupling in MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) syndrome. PLoS One. 2020 Sep 3;15(9):e0238224. doi: 10.1371/journal.pone.0238224. eCollection 2020.

  PMID: 32881886 DERIVED

• Rodan LH, Wells GD, Banks L, Thompson S, Schneiderman JE, Tein I. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome. PLoS One. 2015 May 20;10(5):e0127066. doi: 10.1371/journal.pone.0127066. eCollection 2015.

  PMID: 25993630 DERIVED

MeSH Terms

Conditions

MELAS Syndrome

Interventions

Arginine

Condition Hierarchy (Ancestors)

Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Muscular Diseases; 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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Ingrid Tein, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Neurologist

Study Record Dates

• First Submitted: May 18, 2012
• First Posted: May 22, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 17, 2013

Record last verified: 2013-12

Locations

CA (1)