Efficacy and Safety Evaluation of Metformin Hydrochloride in Myotonic Dystrophy Type 1: A Phase III Randomized, Double-Blind, Multicenter Study

The primary objective of this study is to evaluate the **efficacy** of metformin compared to placebo in improving muscle function in patients with **myotonic dystrophy type 1 (DM1)**. This is clinically relevant as muscle function impairment is a significant symptom of DM1, and improving it could enhance patient mobility and quality of life.

Secondary objectives include:

• To evaluate the safety of metformin in patients with DM1.
• To assess the efficacy of metformin on various functions, including muscle, locomotor, hand-grip strength, thumb-index pinch strength, cardiac, and respiratory functions.
• To evaluate the impact of metformin on the quality of life of patients.

The clinical trial focuses on evaluating the efficacy of metformin versus placebo in improving muscle function in patients with **myotonic dystrophy type 1 (DM1)**. The study population comprises both male and female participants aged between 18 and 70 years. Participants are required to have preserved walking abilities, with stick assistance permissible, and a Muscular Impairment Rating Scale (MIRS) score of 3 or 4. The trial does not include a vulnerable population. Participants must have DM1 confirmed by genetic analysis and be capable of understanding the French language, either independently or with assistance. Women of childbearing potential are required to use effective contraception during the treatment period and up to two days after its conclusion. The sponsor has not provided information regarding the total number of participants. Participants must be affiliated with a social security system and able to provide signed informed consent. The selection process ensures that individuals meet these criteria to participate in the study.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy and safety of **metformin** in patients with **myotonic dystrophy type 1 (DM1)**. The trial is a Phase III, multicenter study with an estimated duration of 52 weeks for each participant. Participants will be randomly assigned in a 1:1 ratio to receive either metformin or a placebo. The primary objective is to assess the improvement in muscle function, as measured by the MFM-32 (Motor Function Measure) scale, from baseline to the final visit at 12 months. Secondary objectives include evaluating the safety of metformin and its effects on various functional and quality of life measures over the same period.

The study will commence with a screening visit to confirm eligibility based on criteria such as age, genetic confirmation of DM1, and preserved walking abilities. Participants must also be able to provide informed consent and have an understanding of the French language or assistance from a relative or medical team. Following successful screening, participants will be enrolled and undergo a baseline visit where initial assessments will be conducted. Subsequent follow-up visits will occur at 6 months and 12 months to monitor progress and collect data on primary and secondary endpoints, including muscle function, locomotor function, hand-grip strength, cardiac and respiratory function, and quality of life.

The expected length of participant involvement is approximately 12 months, with conditions for early termination including withdrawal of consent, significant adverse events, or non-compliance with study procedures. The trial is anticipated to start recruitment in September 2024 and conclude by March 2027. The study aims to provide comprehensive data on the therapeutic potential of metformin in improving the quality of life and functional outcomes for individuals with DM1.

The clinical trial involves the administration of **METFORMIN HYDROCHLORIDE** as the experimental medication. The pharmaceutical form of this medication is a **dispersible tablet**, marketed under the name METFORMINE VIATRIS 500 mg, comprimé dispersible. The active substance, metformin hydrochloride, is of chemical origin. The medication is administered orally, with a maximum daily dose of 3000 mg and a total maximum dose of 1095 g over the course of the study. The treatment period extends up to 52 weeks. The medication is produced by VIATRIS SANTE and is authorized in France under the marketing authorization number NL 32726. The ATC code for metformin is A10BA02, indicating its classification as an antidiabetic medication.

The study also includes a **placebo** treatment, which serves as the comparator in this double-blind, randomized controlled trial. The placebo is designed to mimic the appearance and administration route of the active medication, ensuring blinding is maintained throughout the study. The placebo is administered orally, in a form that is indistinguishable from the METFORMINE VIATRIS 500 mg dispersible tablet, to ensure the integrity of the study's blinding process. The placebo is not associated with any active pharmaceutical ingredient and is used to evaluate the efficacy and safety of metformin in improving muscle function in patients with Myotonic Dystrophy Type I (Steinert’s Disease).

The efficacy of metformin in the treatment of **Myotonic Dystrophy Type I (DM1)** will be assessed through a Phase III prospective, multicenter, randomized, double-blind controlled study. The primary endpoint for evaluating efficacy is the evolution of the MFM-32 (Motor Function Measure) scale scoring, measured from the baseline visit to the final visit at 12 months. Secondary endpoints include the assessment of muscle function at 6 months using the MFM-32 scale, locomotor function via the six-minute walking test, hand-grip strength through MyoGrip scoring, and thumb-index pinch strength using MyoPinch scoring. Additionally, cardiac function will be evaluated by changes in left ventricular ejection fraction, respiratory function by supine vital capacity, and quality of life through QoLgNMD scoring. These assessments will occur at baseline, 6 months, and 12 months.