Clinical trial

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

Name

APHP220832

Description

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.

Trial arms

Trial start

2024-03-01

Estimated PCD

2026-10-01

Trial end

2026-10-01

Status

Not yet recruiting

Phase

Early phase I

Treatment

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.

Arms:

Metformin arm, Placebo receivers

Size

142

Primary endpoint

Change of muscle function

at baseline and 12 months

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 142, 'type': 'ESTIMATED'}}

Updated at

2024-01-31

1 organization

1 product

3 indications

Organization

Assistance Publique - Hôpitaux de Paris

Product

Indication

Indication

Indication