Clinical trial NCT00296621: Effect of Oral Glutamine on Muscle Mass and Function in Duchenne Muscular Dystrophy
Official title: Efficacy Study of Oral Glutamine Supplementation in Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Muscular Dystrophy, Duchenne
Keywords: glutamine
nutrition
children
pediatrics
randomized controlled clinical trial
therapy
supplement
oral administration
handicap
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2006-02-27
Enrollment: 30
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: walking speed at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
Secondary outcomes:
measure: work (kcal) at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
measure: power (kcal/s) at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
measure: 2-minute walk test at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
measure: body composition (bioelectrical impedance analysis) at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
measure: body composition (BIPHOTONIC absorptiometry) at 4,9 months
timeFrame: at 4,9 months
measure: muscle mass (24-h urinary creatinine excretion) at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
measure: indices of protein degradation (CPK and 3-methyl histidine excretion) at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
measure: biochemical parameters (electrolytes, fasting glucose, transaminases, insulin, IgfI, Igf-BP3) at 0,2,4,5,7,9 months
timeFrame: at 0,2,4,5,7,9 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre d'Investigation Clinique, Hôpital Cardiologique, CHR&U de Lille
city: Lille
country: France
facility: Service d'Hépato Gastro Entérologie, Hôpital Jeanne de Flandre, CHR&U de Lille
city: Lille
country: France
facility: Service de Neuropédiatrie, Hôpital Roger Salengro, CHR&U de Lille
city: Paris
country: France
facility: Centre d'Investigation Clinique (CIC9202), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris
city: Poitiers
country: France
facility: Pédiatrie Multidisciplinaire et Nutrition de l'Enfant, Centre Hospitalier Universitaire de Poitiers
Study officials:
affiliation: Centre Hospitalier Universitaire (CHU) de Poitiers
name: Régis Hankard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mok E, Eleouet-Da Violante C, Daubrosse C, Gottrand F, Rigal O, Fontan JE, Cuisset JM, Guilhot J, Hankard R. Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy. Am J Clin Nutr. 2006 Apr;83(4):823-8. doi: 10.1093/ajcn/83.4.823.
citation: Hankard R, Mauras N, Hammond D, Haymond M, Darmaun D. Is glutamine a 'conditionally essential' amino acid in Duchenne muscular dystrophy? Clin Nutr. 1999 Dec;18(6):365-9. doi: 10.1016/s0261-5614(99)80017-x.
citation: Hankard RG, Hammond D, Haymond MW, Darmaun D. Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy. Pediatr Res. 1998 Feb;43(2):222-6. doi: 10.1203/00006450-199802000-00011.
citation: Hankard RG, Haymond MW, Darmaun D. Effect of glutamine on leucine metabolism in humans. Am J Physiol. 1996 Oct;271(4 Pt 1):E748-54. doi: 10.1152/ajpendo.1996.271.4.E748.
citation: Hankard RG, Darmaun D, Sager BK, D'Amore D, Parsons WR, Haymond M. Response of glutamine metabolism to exogenous glutamine in humans. Am J Physiol. 1995 Oct;269(4 Pt 1):E663-70. doi: 10.1152/ajpendo.1995.269.4.E663.
citation: Mok E, Beghin L, Gachon P, Daubrosse C, Fontan JE, Cuisset JM, Gottrand F, Hankard R. Estimating body composition in children with Duchenne muscular dystrophy: comparison of bioelectrical impedance analysis and skinfold-thickness measurement. Am J Clin Nutr. 2006 Jan;83(1):65-9. doi: 10.1093/ajcn/83.1.65.
citation: Mok E, Letellier G, Cuisset JM, Denjean A, Gottrand F, Alberti C, Hankard R. Lack of functional benefit with glutamine versus placebo in Duchenne muscular dystrophy: a randomized crossover trial. PLoS One. 2009;4(5):e5448. doi: 10.1371/journal.pone.0005448. Epub 2009 May 6.