Evaluation of the Efficacy and Safety of Metformin in the Myotonic Dystrophy Type 1 (Steinert's Disease)

NCT ID: NCT05532813

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-29
• Study Completion Date: 2026-12-31

Brief Summary

The study team hypothesize that non-diabetic patients with Myotonic dystrophy type I (DM1) will improve their symptoms, especially their motor deficit which is the main feature of the disease, because of the splicing defect correction by metformin.

The primary objective of the study is to evaluate the efficacy of metformin vs placebo, on the improvement of muscle function in patients with DM1 compared to its placebo.

As the secondary objectives, the study aims:

• To evaluate the safety of metformin on patient with DM1.
• To evaluate the efficacy of metformin vs placebo on:

1. The hand-grip strength;

2. The thumb-index pinch strength;

3. The locomotor function;

4. The respiratory function;

5. The cardiac function;

6. The quality of life;

7. The daily and social activity.

Detailed Description

This is a multicenter, national, comparative study comparing the efficacy and safety of metformin and placebo in patients (1:1 ratio between the 2 groups) with DM1.

Population of study participants: patients with biochemically and/or genetically confirmed DM1 disease already followed in the referral and competence departments, as well as new patients.

All patients will be included by a neuromuscular specialist from French centers participating in the research.

Enrolled patients were randomly assigned (71 patients per group with 1:1 ratio) to either metformin therapy or a placebo, using a centralized randomization procedure.

Metformin or placebo will be administered orally and titrated as recommended in diabetic patients. Initial digestive effects (nausea, vomiting and constipation) of metformin that can be observed in the first days. If digestive tolerance is good, treatment will be increased to a maximum of 1000 mg three times a day i.e. 3000 mg/day after another week. In case of bad digestive tolerance, the dosage should be decrease and the maximum tolerated dosage of metformin should be used. The evaluations of muscle function, walking test, respiratory and cardiac function, quality of life, and tolerance will be assessed at M6 and M12, in the neuromuscular centers. With the estimated effect size, we believe that the inclusion capacities evaluated at 8 to 12 patients per center over one year (18 reference centers involved) will allow to determine a significant difference of MFM score 12 months after inclusion. Dose titration, monitoring of side effects and dose adjustments will be assessed at each visit according to the site endocrinologist advice, if necessary.

Statistical analysis: The difference between the score at 12 months and baseline will be compared between treatment groups using the Student T-test.

Secondary efficacy endpoints evaluating the evolution of symptoms will be analyzed using either a GMM or a GEE for continuous and categorical variables, respectively.

Other quantitative variables will be compared using the Student t-test (or a non-parametric test if the distribution remains skewed following transformation), while categorical variables will be analyzed using either the Chi-squared or the Fisher-exact tests.

All efficacy endpoints will be analysed on an intention-to- treat basis and safety endpoints on a per-protocol basis.

All statistical tests will be performed with a level of significance of 5%. No interim analysis will be performed.

Conditions

Steinert's Disease; Myotonic Dystrophy 1; Metformin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Metformin arm

Patients randomized in Metformin arm will take metformin orally.

Group Type: EXPERIMENTAL

Treatment taken

Intervention Type: DRUG

Treatment (Metformin or placebo) will be administered orally and titrated following the same guideline that metformin in diabetic patient: start with a daily dose of 500 mg twice a day, given during or after meals; then increase to 1000 mg twice a day after a week. If digestive tolerance is good, treatment will be increased to a maximum of 1000 mg three times a day i.e. 3000 mg/day after another week.

Placebo receivers

Patients randomized in placebo arm will take placebo orally in the same procedure as metformin taken.

Group Type: PLACEBO_COMPARATOR

Treatment taken

Intervention Type: DRUG

Treatment (Metformin or placebo) will be administered orally and titrated following the same guideline that metformin in diabetic patient: start with a daily dose of 500 mg twice a day, given during or after meals; then increase to 1000 mg twice a day after a week. If digestive tolerance is good, treatment will be increased to a maximum of 1000 mg three times a day i.e. 3000 mg/day after another week.

Interventions

Treatment taken

Treatment (Metformin or placebo) will be administered orally and titrated following the same guideline that metformin in diabetic patient: start with a daily dose of 500 mg twice a day, given during or after meals; then increase to 1000 mg twice a day after a week. If digestive tolerance is good, treatment will be increased to a maximum of 1000 mg three times a day i.e. 3000 mg/day after another week.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pascal LAFORÊT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Neurology Department, Raymond Poincaré Hospital, APHP

Locations

Neurology Department, Raymond-Poincaré hospital - APHP

Garches, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Pascal LAFORÊT, MD, PhD

Role: CONTACT

pascal.laforet@aphp.fr

+33 (0)1 47 10 77 36

References

Berard C, Payan C, Hodgkinson I, Fermanian J; MFM Collaborative Study Group. A motor function measure for neuromuscular diseases. Construction and validation study. Neuromuscul Disord. 2005 Jul;15(7):463-70. doi: 10.1016/j.nmd.2005.03.004.

Reference Type: BACKGROUND

PMID: 16106528 (View on PubMed)

Landfeldt E, Nikolenko N, Jimenez-Moreno C, Cumming S, Monckton DG, Faber CG, Merkies ISJ, Gorman G, Turner C, Lochmuller H. Change over time in ability to perform activities of daily living in myotonic dystrophy type 1. J Neurol. 2020 Nov;267(11):3235-3242. doi: 10.1007/s00415-020-09970-6. Epub 2020 Jun 15.

Reference Type: BACKGROUND

PMID: 32542526 (View on PubMed)

Other Identifiers

2023-507660-39-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

APHP220832

Identifier Type: -

Identifier Source: org_study_id