Clinical trial NCT01388764: Safety, Tolerability and Effects of L-Arginine in Boys With Dystrophinopathy on Corticosteroids
Official title: Pilot Study: To Assess the Safety, Tolerability and Effects of L-Arginine on Muscles in Boys With Dystrophinopathy on Corticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dystrophinopathy
Duchenne Muscular Dystrophy
Becker's Muscular Dystrophy
Keywords: L-arginine supplement study
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-07-07
Enrollment: 7
Sex: MALE
Minimum age (years): 7
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: MRI/MRS of calf muscle
timeFrame: Day 0 and Day 30
Secondary outcomes:
measure: Blood tests
timeFrame: Day 0 and Day 30
measure: Assessment of muscle strength and function
timeFrame: Day 0 and Day 30
measure: Pulmonary function tests
timeFrame: Day 0 and Day 30
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Namita Goyal, MD
role: PRINCIPAL_INVESTIGATOR
References: