Effect of Oral Glutamine on Muscle Mass and Function in Duchenne Muscular Dystrophy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether long-term oral glutamine supplementation is effective in improving muscle mass and function in children with Duchenne muscular dystrophy (DMD).

Detailed Description
-----------------
Glutamine inhibits whole body protein degradation in children with Duchenne Muscular Dystrophy (DMD). The effect is observed after 5 h oral glutamine administration and is also found when glutamine is given over a 10-day period. This multi-site national study aims to evaluate the functional benefit of long-term oral glutamine administration in 30 DMD children using a randomized double-blind placebo-controlled cross-over design. The study includes two 4-month periods: 1) a treatment period in which the subject receives oral glutamine (0.5 g/kg/d) and 2) a control period in which the subject receives a placebo. The order of treatment allocation is randomized. The two 4-month periods are separated by a 1 month wash-out period. The children are monitored every 2 months during period 1 (M0, M2, M4) and period 2 (M5, M7, M9) in the clinical investigation centres of Hospital Robert Debré in Paris and the CHR&U de Lille, as well as the clinical research centre of the CHU de Poitiers. Evidence of a functional benefit would involve evaluating the administration of glutamine over longer periods (as early as possible following diagnosis) among severely handicapped children and in other chronic pathologies associated with increased muscle protein catabolism. In DMD, such evidence would enable children to undergo gene therapy under improved physical condition. Comparisons: Glutamine administration compared to placebo on the following outcome measures: walking speed on a standard course, work (kcal) and power (kcal/s) in relation to effort, body composition (bioelectrical impedance analysis and BIPHOTONIC absorptiometry), muscle mass (24-h urinary creatinine excretion), indices of protein degradation (CPK and 3-methyl histidine excretion) and biochemical parameters (electrolytes, fasting glucose, transaminases, insulin, IgfI, Igf-BPI).

Official Title
-----------------
Efficacy Study of Oral Glutamine Supplementation in Duchenne Muscular Dystrophy

Conditions
-----------------
Muscular Dystrophy, Duchenne

Intervention / Treatment
-----------------
* Drug: L-Glutamine
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of Duchenne muscular dystrophy Able to walk >170 m Absence of hepatic insufficiency Absence of renal insufficiency Exclusion Criteria: Dependent upon wheelchair Body weight >60kg Liver failure Kidney failure Surgery scheduled during the year following the first visit
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: L-Glutamine<br>* L-Glutamine<br>|
| Placebo Comparator: 2<br> | Drug: placebo<br>* placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| walking speed at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| work (kcal) at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 
| power (kcal/s) at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 
| 2-minute walk test at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 
| body composition (bioelectrical impedance analysis) at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 
| body composition (BIPHOTONIC absorptiometry) at 4,9 months |  | at 4,9 months | 
| muscle mass (24-h urinary creatinine excretion) at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 
| indices of protein degradation (CPK and 3-methyl histidine excretion) at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 
| biochemical parameters (electrolytes, fasting glucose, transaminases, insulin, IgfI, Igf-BP3) at 0,2,4,5,7,9 months |  | at 0,2,4,5,7,9 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
glutamine, nutrition, children, pediatrics, randomized controlled clinical trial, therapy, supplement, oral administration, handicap