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

Duchenne Muscular Dystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01388764
• Other study ID #: 2011D001591
• Status: Completed
• Phase: Phase 1
• First received: July 5, 2011
• Last updated: June 30, 2012
• Start date: January 2012
• Est. completion date: May 2012

Study information

• Verified date: June 2012
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 7 Years to 11 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Becker's Muscular Dystrophy
• Duchenne Muscular Dystrophy
• Dystrophinopathy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

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)

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	Pulmonary function tests	Subjects will have pulmonary function studies to assess forced vital capacity	Day 0 and Day 30	No