Myotonic dystrophy type 1 (DM1) also known as Steinert disease
Conditions
Interventions
Trade Name: metformin 500mg
Pharmaceutical Form: Tablet
INN or Proposed INN: METFORMIN
CAS Number: 657-24-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pha
Sponsors
Centre d'Etude des Cellules Souches (CECS)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: Serious concomitant medical disorder, evidence of renal dysfunction (creatinine clearance 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 To determine the safety of metformin 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety: Overall incidence of adverse events and serious adverse events as well as laboratory assessments will be evaluated for each arm and for the study as a whole. Efficacy: MyoTone test (performed with the hand grip) at W52: improvement = 20% of relaxation phase from baseline Muscle MRI at W52: stabilization from baseline of the volume of residual muscle tissue in TA muscle, of the mean T2-relaxation-time of residual muscle tissue, and of the mean fat-to-water ratio in the entire TA muscle Insulin resistance, cholesterol and triglycerides will be measured and compared to baseline over time Muscle function and strength measured by the grip test (Handgrip) and the Quantitative Muscle Testing (QMT) test at W52: improvement = 5% of the muscle strength from baseline Cardiac: 12-lead resting ECG will be analyzed at W52 compared to baseline Activity and social participation: Scores of DM1-Activ scale and InQoL questionnaires at baseline and over 52 weeks will be analyzed Biomarker Assays: Change of level in blood INSRA and INSRB Messenger Ribonucleic Acid (mRNA), FAS ATP2A1 and LMNA splice variants from screening, W2, W4, W16, and W52;Timepoint(s) of evaluation of this end point: Safety will be evaluated during the whole study. Efficacy endpoints will be evaluated at week 52 compared to baseline. Biomarkers will be mesured at screening, at Week 2, Week 4, Week 16, and Week 52 | — |
Countries
France
Contacts
Public ContactClinical Trial Information
CECS
Outcome results
None listed