search
Back to results

L-citrulline and Metformin in Duchenne's Muscular Dystrophy

Primary Purpose

Duchenne's Muscular Dystrophy (DMD)

Status
Completed
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
750 mg metformin and 7.5 g L-citrulline daily p.o.
Placebo
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Duchenne's Muscular Dystrophy (DMD) focused on measuring Duchenne's muscular dystrophy, DMD

Eligibility Criteria

78 Months - 10 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

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

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mean change of MFM total score, the D2, and D3 MFM subscores
Mean change of six minute walking distance (6MWD)
Change of quantitative muscle MRI (Magnetic Resonance Imaging) including muscle fat content (MFC) and T2 times of thigh muscles
Change in the plasma/urine concentration for markers of muscle necrosis, oxidative stress, nitrosative stress, and change of microRNA (miRNA)
Mean change of quantitative muscle force (QMT) of knee extension and elbow flexion using hand held dynamometry (HHD)

Full Information

First Posted
November 20, 2013
Last Updated
April 17, 2018
Sponsor
University Hospital, Basel, Switzerland
search

1. Study Identification

Unique Protocol Identification Number
NCT01995032
Brief Title
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

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Data Monitoring Committee
No

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne's Muscular Dystrophy (DMD)
Keywords
Duchenne's muscular dystrophy, DMD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
750 mg metformin and 7.5 g L-citrulline daily p.o.
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
metformin placebo and L-citrulline placebo 3 times daily p.o. for 26 weeks
Intervention Type
Drug
Intervention Name(s)
750 mg metformin and 7.5 g L-citrulline daily p.o.
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers)
Time Frame
baseline to week 26
Secondary Outcome Measure Information:
Title
Mean change of MFM total score, the D2, and D3 MFM subscores
Time Frame
baseline to week 26
Title
Mean change of six minute walking distance (6MWD)
Time Frame
baseline to week 26
Title
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
Title
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
Title
Mean change of quantitative muscle force (QMT) of knee extension and elbow flexion using hand held dynamometry (HHD)
Time Frame
baseline to week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
78 Months
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk Fischer, MD
Organizational Affiliation
University Children's Hospital Basel
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Children's Hospital
City
Basel
State/Province
BS
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
31664444
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.
Results Reference
derived
PubMed Identifier
27488051
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.
Results Reference
derived

Learn more about this trial

L-citrulline and Metformin in Duchenne's Muscular Dystrophy

We'll reach out to this number within 24 hrs