Duchenne's Muscular Dystrophy (DMD)Phase 3NCT01995032
L-citrulline and Metformin in Duchenne's Muscular Dystrophy
A Phase 3 study testing 750 mg metformin and 7.5 g L-citrulline daily p.o. in people with Duchenne's Muscular Dystrophy (DMD), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 78 months to 10 years
- Conditions the study is for
- Duchenne's Muscular Dystrophy (DMD)
- What is being tested?
- 750 mg metformin and 7.5 g L-citrulline daily p.o.
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteSwitzerland
- Study dates
- Oct 2013to Mar 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 78 months to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Children's Hospital
Basel, Canton of Basel-City, 4031
About this study
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"
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.
Read the 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
- Conditions
- Duchenne's Muscular Dystrophy (DMD)
- Being tested
- 750 mg metformin and 7.5 g L-citrulline daily p.o., Placebo
- Keywords
- Duchenne's muscular dystrophy, DMD
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
750 mg metformin and 7.5 g L-citrulline daily p.o.Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers)
Measured: baseline to week 26
Secondary outcomes (5)
Mean change of MFM total score, the D2, and D3 MFM subscores
Measured: baseline to week 26
Mean change of six minute walking distance (6MWD)
Measured: baseline to week 26
Change of quantitative muscle MRI (Magnetic Resonance Imaging) including muscle fat content (MFC) and T2 times of thigh muscles
Measured: baseline to week 26
Change in the plasma/urine concentration for markers of muscle necrosis, oxidative stress, nitrosative stress, and change of microRNA (miRNA)
Measured: baseline to week 26
Mean change of quantitative muscle force (QMT) of knee extension and elbow flexion using hand held dynamometry (HHD)
Measured: baseline to week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2013 (estimated)
- Study startOct 2013
- Primary completionOct 2015
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Duchenne's Muscular Dystrophy (DMD)Studies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dirk Fischer, MD, Principal investigator, University Children's Hospital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01995032
- Sponsor's protocol ID
- DMD02
- Status last verified
- Apr 2018
- First submitted
- 20 Nov 2013
- Last updated
- 19 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 31664444Hafner 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.
PubMed 27488051
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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"
- ClinicalTrials.gov ID
- NCT01995032
- Acronym / sponsor ID
- DMD02
- Conditions
- Duchenne's Muscular Dystrophy (DMD)
- Keywords
- Duchenne's muscular dystrophy, DMD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 26 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 750 mg metformin and 7.5 g L-citrulline daily p.o. | Experimental | Drug: 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 |
| Placebo | Placebo comparator | Drug: Placebometformin placebo and L-citrulline placebo 3 times daily p.o. for 26 weeks |
Who may qualify
- Ages
- 78 months to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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%
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers)
Time frame: baseline to week 26
5 secondary outcomes
Mean change of MFM total score, the D2, and D3 MFM subscores
Time frame: baseline to week 26
Mean change of six minute walking distance (6MWD)
Time frame: baseline to week 26
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
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
Mean change of quantitative muscle force (QMT) of knee extension and elbow flexion using hand held dynamometry (HHD)
Time frame: baseline to week 26
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2018.
- Derived from this study: PubMed 31664444Hafner 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.
- Derived from this study: PubMed 27488051Hafner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dirk Fischer, MD principal investigator
University Children's Hospital Basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 750 mg metformin and 7.5 g L-citrulline daily p.o. in people with Duchenne's Muscular Dystrophy (DMD), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change of motor function measure (MFM) D1 subscore (assessing standing and transfers) (time frame: baseline to week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01995032, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2018.