Metformin to improve muscle strength in myotonic dystrophy type 1

Evaluation of the Efficacy and Safety of Metformin in the Myotonic Dystrophy Type 1 (Steinert's Disease). A Phase III, Prospective, Multicentre, Randomized, Double-blind Controlled Study

This will test whether taking metformin can improve muscle strength and daily function in adults with myotonic dystrophy type 1 who can still walk.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 142 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Garches)
• Trial ID: NCT05532813 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, placebo-controlled Phase 3 trial in France compares oral metformin versus placebo in adults with genetically confirmed myotonic dystrophy type 1 and preserved walking ability. Participants are randomized 1:1 (about 71 per group) and receive metformin titrated up to a maximum of 1000 mg three times daily or matching placebo, with dose adjustments for gastrointestinal tolerance. Muscle function, hand-grip and pinch strength, walking tests, respiratory and cardiac function, quality of life, and safety are assessed at 6 and 12 months. The trial aims to determine whether metformin leads to measurable improvements in motor function and daily activity compared with placebo.

Who should consider this trial

Good fit: Adults aged 18–70 with genetically confirmed DM1, preserved walking ability (MIRS 3–4), able to consent, and not pregnant or planning pregnancy are ideal candidates.

Not a fit: Patients with severe respiratory or cardiac impairment, creatinine clearance below 50 ml/min, those requiring prolonged ventilatory support, or with contraindications to metformin are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, metformin could improve muscle strength, walking ability, and day-to-day quality of life for people with DM1.

How similar studies have performed: Preclinical work and small early clinical studies have suggested metformin may correct splicing defects and improve muscle outcomes in DM1, but larger randomized trials like this are needed for confirmation.

Eligibility criteria

Inclusion Criteria:

* DM1 disease confirmed by genetic analysis
* Men and women between 18 and 70 years of age.
* Preserved walking abilities (stick assistance possible)
* MIRS score 3 or 4
* Women of childbearing potential under efficient contraception during treatment
* Patient able to consent
* All patients who have completed and signed the specific information and informed consent form
* Affiliation to a social security system

Exclusion Criteria:

* Pregnant or breast-feeding women
* Men with an intention to conceive a child during the time of the study
* Contraindications to Metformin (hypersensitivity to metformin or to one of the excipients)
* Respiratory:

  * Patient requiring tracheotomy or
  * Patient requiring non-invasive-ventilation: - more than 12 hours per day; - insufficiently ventilated
* Creatinine clearance inferior to 50 ml/min
* Cardiac:

  * Left ventricular ejection fraction below 35%
  * Conduction system disease on the electrocardiogram with PR interval \>200 ms or QRS duration \>110 ms without a pacemaker or an implantable defibrillator or cardiac electrophysiological study performed over the past 5 years
  * Third-degree or Second degree type II atrioventricular block without a pacemaker or an implantable defibrillator
  * Sustained ventricular tachycardia
* Acute disease that may lead to tissue hypoxia

Where this trial is running

Garches

• Neurology Department, Raymond-Poincaré hospital - APHP — Garches, France (Recruiting)

Study contacts

• Principal investigator: Pascal LAFORÊT, MD, PhD — Neurology Department, Raymond Poincaré Hospital, APHP
• Study coordinator: Pascal LAFORÊT, MD, PhD

Conditions Steinert's Disease; Myotonic Dystrophy 1; Metformin; Muscle function