L-citrulline and Metformin in Duchenne's Muscular Dystrophy

• ClinicalTrials.gov Identifier: NCT01995032
• Recruitment Status: Completed
• First Posted: November 26, 2013
• Last Update Posted: April 19, 2018
• 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, Klein A, Rubino D, Gocheva V, Schmidt S, Schroeder J, Bernert G, Laugel V, Steinlin M, Capone A, Gloor M, Bieri O, Hemkens LG, Speich B, Zumbrunn T, Gueven N, Fischer D. Effect of Combination l-Citrulline and Metformin Treatment on Motor Function in Patients With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA Netw Open. 2019 Oct 2;2(10):e1914171. doi: 10.1001/jamanetworkopen.2019.14171.

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
• 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