L-citrulline and Metformin in Duchenne's Muscular Dystrophy

• Sponsor: University Hospital, Basel, Switzerland
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Duchenne's Muscular Dystrophy (DMD)	Drug: 750 mg metformin and 7.5 g L-citrulline daily p.o.; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: "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"
• Study Start Date: October 2013
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: March 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: 750 mg metformin and 7.5 g L-citrulline daily p.o.
Placebo Comparator: Placebo; metformin placebo and L-citrulline placebo 3 times daily p.o. for 26 weeks	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers) [ Time Frame: baseline to week 26 ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 78 Months to 10 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Switzerland

University Children's Hospital

Basel, BS, Switzerland, 4031

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Investigators

• Principal Investigator: Dirk Fischer, MD; University Children's Hospital Basel

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hafner P, Bonati U, Rubino D, Gocheva V, Zumbrunn T, Gueven N, Fischer D. Treatment with L-citrulline and metformin in Duchenne muscular dystrophy: study protocol for a single-centre, randomised, placebo-controlled trial. Trials. 2016 Aug 3;17(1):389. doi: 10.1186/s13063-016-1503-1.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT01995032 History of Changes
• Other Study ID Numbers: DMD02
• First Posted: November 26, 2013
• Last Update Posted: April 19, 2018
• Last Verified: April 2018

Keywords provided by University Hospital, Basel, Switzerland:

Duchenne's muscular dystrophy; DMD

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs