L-citrulline and Metformin in Duchenne's Muscular Dystrophy

Phase 3

Completed

• Conditions: Duchenne's Muscular Dystrophy (DMD)
• Interventions: Drug: 750 mg metformin and 7.5 g L-citrulline daily p.o.; Drug: Placebo

• Registration Number: NCT01995032
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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

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

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-11-20
• Study First Submitted QC: 2013-11-20
• Study First Posted: 2013-11-26
• Primary Completion: 2015-10
• Study Completion: 2016-03
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-17
• Last Update Posted: 2018-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
750 mg metformin and 7.5 g L-citrulline daily p.o.	750 mg metformin and 7.5 g L-citrulline daily p.o.	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
Placebo	Placebo	metformin placebo and L-citrulline placebo 3 times daily p.o. for 26 weeks

Primary Outcome Measures

Name	Time	Method
Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers)	baseline to week 26

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University Children's Hospital; 🇨🇭 Basel, BS, Switzerland