Clinical trial NCT01995032: L-citrulline and Metformin in Duchenne's Muscular Dystrophy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Duchenne's Muscular Dystrophy (DMD)
Keywords: Duchenne's muscular dystrophy
DMD
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2013-11-26
Enrollment: 47
Sex: ALL
Minimum age (years): 78
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers)
timeFrame: baseline to week 26
Secondary outcomes:
measure: Mean change of MFM total score, the D2, and D3 MFM subscores
timeFrame: baseline to week 26
measure: Mean change of six minute walking distance (6MWD)
timeFrame: baseline to week 26
measure: Change of quantitative muscle MRI (Magnetic Resonance Imaging) including muscle fat content (MFC) and T2 times of thigh muscles
timeFrame: baseline to week 26
measure: Change in the plasma/urine concentration for markers of muscle necrosis, oxidative stress, nitrosative stress, and change of microRNA (miRNA)
timeFrame: baseline to week 26
measure: Mean change of quantitative muscle force (QMT) of knee extension and elbow flexion using hand held dynamometry (HHD)
timeFrame: baseline to week 26
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Children's Hospital
state: BS
Study officials:
affiliation: University Children's Hospital Basel
name: Dirk Fischer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.