Safety, Tolerability and Effects of L-Arginine in Boys With Dystrophinopathy on Corticosteroids

Pilot Study: To Assess the Safety, Tolerability and Effects of L-Arginine on Muscles in Boys With Dystrophinopathy on Corticosteroids

The purpose of the study is to assess the safety, tolerability, and effects of L-Arginine on muscles in boys with dystrophinopathy on corticosteroids. Specifically, to see if L-arginine reduces muscle signal abnormalities on MRI done pre and post 30 days of L-arginine administration.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy; Dystrophinopathy; Becker's Muscular Dystrophy
• Intervention / Treatment: Drug: L-arginine

Detailed Description

Dystrophinopathy is a muscular dystrophy (includes Duchenne or Becker's Muscular Dystrophy) that can be a lethal muscle disorder resulting from defects in the gene for dystrophin, a structural protein required to maintain muscle integrity. Absence of functional dystrophin leaves the muscle membrane vulnerable to damage during contraction. This damage can be exacerbated by an inflammatory response leading to myofiber necrosis.

L-arginine is a widely available dietary supplement amino acid postulated to affect dystrophinopathy in several favorable ways: upregulation of utrophin, vasodilation in muscle via nitric oxide, enhanced synthesis of creatine, increase levels of growth hormone.

We hypothesize that administration of L-arginine may increase levels of creatine and growth hormone and in turn reduce the extent of myofiber damage in our patients with dystrophinopathy

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Confirmation of diagnosis of dystrophinopathy, documented by clinical exam and dystrophin DNA mutation analysis
• Ambulatory male subjects between the ages of 7-11 years
• Stable dosage of corticosteroids for 3 months prior to entry (Screening/Baseline Day 0) and during treatment period
• Able to follow instructions and give assent
• Able to complete nonsedated MR

Exclusion Criteria:

• Presence of metallic orthopedic hardware in the lower extremity that could affect MRI/MRS measurements
• Routine MRI exclusion criteria such as the presence of a pacemaker, cochlear implant, or cerebral aneurysm clip
• Subjects not capable of cooperating during MR examination
• Known hypersensitivity to L-arginine
• Exposure to another investigational agent, investigational supplements, growth hormone within 3 months prior to entry (Screening/Baseline Day 0) or during treatment period
• Subjects must not be taking L-arginine for at least 4 weeks prior to entry (Day 0)
• Subjects who are non-ambulatory or with daytime ventilatory dependence

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-arginine	Drug: L-arginine; Subjects will receive oral L-Arginine (0.3 grams/kg/day, divided 2 times per day, not to exceed 14 grams/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI/MRS of calf muscle	MRI/MRS will be performed of the calf muscle in all subjects (N=8) to assess muscle signal abnormalities on MRI and creatine levels on MRS, done at the start of the study (Day 0) and at the end of the study (Day 30), after 30 days of L-arginine administration.	Day 0 and Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood tests	We will obtain safety labs [complete blood count (CBC) and comprehensive metabolic panel (CMP)] from all subjects (N =8), at day 0 and day 30, after 30 days of oral L-argninine administration.	Day 0 and Day 30
Assessment of muscle strength and function	Measurements of upper and lower extremity strength will be performed using a hand-held dynamometer. Functional tests will also be performed which include time to walk specified distances and time to climb stairs.	Day 0 and Day 30
Pulmonary function tests	Subjects will have pulmonary function studies to assess forced vital capacity	Day 0 and Day 30

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Namita Goyal, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: July 5, 2011
• First Posted (Estimate): July 7, 2011

Study Record Updates

• Last Update Posted (Estimate): July 3, 2012
• Last Update Submitted That Met QC Criteria: June 30, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: L-arginine supplement study
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 2011D001591