A phase II study of metformin in myotonic dystrophy type 1 patients
- Conditions
- Myotonic dystrophy type 1 (DM1) also known as Steinert diseaseTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2013-001732-21-FR
- Lead Sponsor
- Centre d'Etude des Cellules Souches (CECS)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
A diagnosis of DM1, confirmed by DM1 genetic mutation
Male or female patients, age =18 to = 60 years
Muscular Impairment Rating Scale (MIRS) score 2 or 3
Ambulatory, able to perform the 6 Minute Walk Test (6MWT)
All laboratory parameters must be grade 0 or 1 (as per CTCAE criteria) except for AST, ALT for which a grade 2 will be allowed if stated non clinically significant
For women of child-bearing potential, i.e. with no history of hysterectomy or tubal ligation, use of one effective method of birth control during the conduct of the study
Written informed consent
Patient covered by a national health insurance scheme affiliated with the French healthcare system
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Serious concomitant medical disorder, evidence of renal dysfunction (creatinine clearance < 60 ml/min), blood dyscrasia, hepatic insufficiency, symptomatic pancreatitis, cardiac diseases not controlled, congestive heart failure (NYHA score > 3), cardiac rhythm anomalies (supra-ventricular or ventricular) not controlled or severe conduction abnormalities (AVB I, II or III or HV > 70 ms) without medical device (patients with pacemaker could be included) [echocardiography in the year before the inclusion], congenital heart defect, known history of heart attack, metabolic acidosis, hypertension, significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than DM1
History of psychiatric conditions including, but not limited to, psychosis, suicidal ideations, or major depression. Patients with mild to moderate depression in the past may be enrolled if, in the Investigator’s opinion, they are suitable for treatment
Drug or alcohol abuse within 12 months of enrollment
Other medical condition (besides DM1) that would significantly impact ambulation
Any history of malignancy except for cases of remission (remission > 12 months) and surgically cured skin cancer or pilomatricoma (benign tumor of the hair follicle that is associated with DM1)
Vital capacity < 60% or total lung capacity < 60%, hypercapnia (PCO2 = 50 mmHg)
or other signs of poor respiratory status which is expected to require the initiation of BiPAP within the study period (patients with nocturnal non-invasive ventilation CPAP or BiPAP could be included)
Use of medications intended for the treatment of DM1 including glucocorticoids, anabolic steroids, testosterone, growth hormone, or insulin-like growth factor I (IGF-I) within 1 year of entry
Any medical contraindications to metformin
Known allergy to metformin and/or his excipients
Symptomatic insulin requiring diabetes or type 2 diabetes requiring oral anti-diabetic agents
Women who are pregnant or breast-feeding
Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period (participation in natural history study is allowed)
Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study
Patient unable or unwilling to comply with the protocol requirements
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of metformin on ambulation in patients with myotonic dystrophy type 1.;Secondary Objective: To determine the efficacy of metformin on myotonia, insulin resistance, cholesterol and triglycerides, muscle function and strength, quality of life, gastrointestinal function, and cardiac function<br>To determine the safety of metformin<br>To determine the INSRA and INSRB Messenger Ribonucleic Acid (mRNA) ratio in blood, as well as FAS ATP2A1 and LMNA splice variants;Primary end point(s): Efficacy: At week 52, change from baseline in distance walked at the 6MWT (6MWT);Timepoint(s) of evaluation of this end point: Evaluation at week 52
- Secondary Outcome Measures
Name Time Method