L-citrulline and Metformin in Duchenne's Muscular Dystrophy

NCT01995032 | Completed Phase 3

• 1 other identifier: DMD02
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Duchenne's Muscular Dystrophy (DMD)

Keywords

Duchenne's muscular dystrophy; DMD

Outcome Measures

Primary Outcomes (1)

• Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers)

  baseline to week 26

Secondary Outcomes (5)

• 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

Study Arms (2)

750 mg metformin and 7.5 g L-citrulline daily p.o.

EXPERIMENTAL

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

PLACEBO COMPARATOR

metformin placebo and L-citrulline placebo 3 times daily p.o. for 26 weeks

Drug: Placebo

Interventions

750 mg metformin and 7.5 g L-citrulline daily p.o. DRUG

750 mg metformin and 7.5 g L-citrulline daily p.o.

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 78 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Children's Hospital

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 31664444 DERIVED

• 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.

  PMID: 27488051 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

Metformin

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Dirk Fischer, MD

  University Children's Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 26, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: March 1, 2016
• Last Updated: April 19, 2018

Record last verified: 2018-04

Locations

CH (1)