L-citrulline and Metformin in Duchenne's Muscular Dystrophy

Study Overview
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Brief Summary
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The purpose of the study is to show that the intake of L-citrulline and metformin improves muscle function and delay of progression in patients with Duchenne's muscular dystrophy.

Detailed Description
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This is a single center, randomized, double-blind, placebo controlled study. The study medication consists of L-citrulline and metformin, respectively placebo given orally; 2.5 g L-citrulline or placebo will be given 3 times daily, metformin containing 250 mg or placebo will be administered 3 times daily. The duration of the study is 26 weeks and comprehends one screening and three study visits. Amendment 1: Amended eligibility criteria

Official Title
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A Double Blind Randomised Placebo Controlled Efficacy and Safety Study of L-citrulline and Metformin in Ambulant Children Aged Between 7 and 10 Years With Duchenne's Muscular Dystrophy

Conditions
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Duchenne's Muscular Dystrophy (DMD)

Intervention / Treatment
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* Drug: 750 mg metformin and 7.5 g L-citrulline daily p.o.
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Molecular diagnosis of DMD Patients 6.5 - 10 years of age at time of screening Ambulant Ability to walk 150 m in the 6 min walking distance (6MWT) D1 subdomain of the MFM scale >40% stable treatment with steroids for >6 months or steroid naïve patients Exclusion Criteria: Previous (3 months or less) or concomitant participation in another therapeutic trial Use of L-citrulline, L-arginine or metformin within the last 3 months Known individual hypersensitivity to L-citrulline or metformin known or suspected malignancy Other chronic disease or clinical relevant limitation of renal, liver, heart function according to discretion of investigator start of cortisone treatment or change in dosage <6 months prior to screening

Ages Eligible for Study
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Minimum Age: 78 Months
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 750 mg metformin and 7.5 g L-citrulline daily p.o.<br>7.5 g L-citrulline p.o. and 750 mg metformin daily p.o. (3x 2.5 g, respectively 3x 250 mg) for 26 weeks | Drug: 750 mg metformin and 7.5 g L-citrulline daily p.o.<br> <br> |
| Placebo Comparator: Placebo<br>metformin placebo and L-citrulline placebo 3 times daily p.o. for 26 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers) |  | baseline to week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of MFM total score, the D2, and D3 MFM subscores |  | baseline to week 26 | 
| Mean change of six minute walking distance (6MWD) |  | baseline to week 26 | 
| Change of quantitative muscle MRI (Magnetic Resonance Imaging) including muscle fat content (MFC) and T2 times of thigh muscles |  | baseline to week 26 | 
| Change in the plasma/urine concentration for markers of muscle necrosis, oxidative stress, nitrosative stress, and change of microRNA (miRNA) |  | baseline to week 26 | 
| Mean change of quantitative muscle force (QMT) of knee extension and elbow flexion using hand held dynamometry (HHD) |  | baseline to week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne's muscular dystrophy, DMD