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

Muscular Dystrophy, Duchenne Clinical Trial

— MDB-GLN  

Official title:

Efficacy Study of Oral Glutamine Supplementation in Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00296621
• Other study ID #: P030420
• Secondary ID: AOM 03 121
• Status: Completed
• Phase: Phase 2
• First received: February 23, 2006
• Last updated: December 20, 2007
• Start date: February 2006
• Est. completion date: November 2007

Study information

• Verified date: December 2007
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2007
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• L-Glutamine
L-Glutamine
• placebo
placebo

Locations

Country	Name	City	State
France	Centre d'Investigation Clinique, Hôpital Cardiologique, CHR&U de Lille	Lille
France	Service d'Hépato Gastro Entérologie, Hôpital Jeanne de Flandre, CHR&U de Lille	Lille
France	Service de Neuropédiatrie, Hôpital Roger Salengro, CHR&U de Lille	Lille
France	Centre d'Investigation Clinique (CIC9202), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris	Paris
France	Pédiatrie Multidisciplinaire et Nutrition de l'Enfant, Centre Hospitalier Universitaire de Poitiers	Poitiers

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View Citation

Mok E, Béghin 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. — View Citation

Mok E, Eléouet-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	walking speed at 0,2,4,5,7,9 months		at 0,2,4,5,7,9 months	Yes
Secondary	work (kcal) at 0,2,4,5,7,9 months		at 0,2,4,5,7,9 months	Yes
Secondary	power (kcal/s) at 0,2,4,5,7,9 months		at 0,2,4,5,7,9 months	Yes
Secondary	2-minute walk test at 0,2,4,5,7,9 months		at 0,2,4,5,7,9 months	Yes
Secondary	body composition (bioelectrical impedance analysis) at 0,2,4,5,7,9 months		at 0,2,4,5,7,9 months	Yes
Secondary	body composition (BIPHOTONIC absorptiometry) at 4,9 months		at 4,9 months	Yes
Secondary	muscle mass (24-h urinary creatinine excretion) at 0,2,4,5,7,9 months		at 0,2,4,5,7,9 months	Yes
Secondary	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	Yes
Secondary	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	Yes

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