Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
203
Countries
1
Sites
15
Myotonic dystrophy type 1 (DM1)
To evaluate the efficacy of metformin vs placebo, on the improvement of muscle function in DM1 patients.
Key facts
- Sponsor
- Assistance Publique Hopitaux De Paris
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 3 Dec 2024 → ongoing
- Decision date (initial)
- 2024-06-24
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- Programme Hospitalier de Recherche Clinique - PHRC 2021 (French Ministry of Health)
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To evaluate the efficacy of metformin vs placebo, on the improvement of muscle function in DM1 patients.
Secondary objectives 9
- • To evaluate the safety of metformin on patient with DM1
- • To evaluate the efficacy of metformin on muscle function
- To evaluate the efficacy of metformin on locomotor function
- To evaluate the efficacy of metformin on hand-grip strength
- To evaluate the efficacy of metformin on thumb-index pinch strength
- To evaluate the efficacy of metformin on respiratory function
- To evaluate the efficacy of metformin on quality of life
- - To evaluate the efficacy of metformin on cognitive function using the evolution SDMT and Stroop interference naming scoring between the baseline visit, the visit at 6 months and the final visit at 12 months.
- To evaluate the efficacy of metformin on cardiac function
Conditions and MedDRA coding
Myotonic dystrophy type 1 (DM1)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10068862 | Steinert disease | 10010331 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | METFORMYO A phase III multicenter, national, comparative, randomized, controlled, double-blinded study comparing the efficacy and safety of metfomin and placebo in patients with DM1.
Participants will be distributed in a 1:1 ratio between the 2 groups.
|
Randomised Controlled | Double | [{"id":134521,"code":4,"name":"Analyst"},{"id":134525,"code":5,"name":"Carer"},{"id":134524,"code":2,"name":"Investigator"},{"id":134522,"code":3,"name":"Monitor"},{"id":134523,"code":1,"name":"Subject"}] | Metformin, 500 mg, dispersible: Metformin will be administered orally and titrated as recommended in diabetic patients: 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 of metformine 500 mg: 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 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- DM1 disease confirmed by genetic analysis
- Men and women between 18 and 70 years of age
- Preserved walking abilities (stick assistance possible)
- MIRS (Muscular Impairment Rating Scale) 3 or 4
- Women of childbearing potential under efficient contraception during treatment and up to 2 days after the end of the experimental treatment
- Ability to provide signed informed consent
- Capacity of the patient to understand French language or presence of a relative (or the medical team) who can help the patient understand the study.
- Affiliation to a social security system
Exclusion criteria 9
- Diabetic patient
- Patient already taking metformin
- Pregnant or breast-feeding women
- Men with an intention to conceive a child during the time of the study
- Contraindications to Metformin: o All types of acute metabolic acidosis o Acute conditions that may impair renal function, such as: dehydration, severe infection, shock o Hepatocellular insufficiency, acute alcohol intoxication, alcoholism o Hypersensitivity to metformin or to one of the excipients o Acute disease that may lead to tissue hypoxia such as decompensated heart failure, acute respiratory failure, recent myocardial infarction. - Respiratory contraindications: o Patient requiring tracheotomy or o Patient requiring non-invasive-ventilation: - more than 12 hours per day - insufficiently ventilated
- Creatinine clearance inferior to 60 ml/min (MDRD).
- Cardiac contraindications: o Left ventricular ejection fraction below 35% o 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 has been performed o Third-degree or Second degree type II atrioventricular block without a pacemaker or an implantable defibrillator o Sustained ventricular tachycardia o Acute cardiac failure o Myocardial infarction of less than three months
- Patient participating in another interventional clinical trial
- Patient under legal protection (curatorship, tutorship)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is the evolution of the MFM-32 (Motor Function Measure) scale scoring between the baseline visit and the final visit at 12 months.
Secondary endpoints 8
- To evaluate the safety of metformin in DM1 patient using the collection of serious adverse event during the 12 months of treatment.
- To evaluate the efficacy on metformin on muscle function at 6 months using the evolution of MFM-32 scale scoring between the baseline visit and the visit at 6 months as endpoint.
- To evaluate the efficacy of metformin on locomotor function using the evolution of six minutes walking test scoring between the baseline visit, the visit at 6 months and the final visit at 12 months as endpoints.
- To evaluate the efficacy of metformin on hand-grip strength using the evolution of MyoGrip scoring between the baseline visit, the visit at 6 months and the final visit at 12 months as endpoints.
- To evaluate the efficacy of metformin on thumb-index pinch strength using the evolution of MyoPinch scoring between the baseline visit, the visit at 6 months and the final visit at 12 months as endpoints.
- To evaluate the efficacy of metformin on respiratory function using the evolution of supine vital capacity between the baseline visit, the visit at 6 months and the final visit at 12 months as endpoints.
- To evaluate the efficacy of metformin on quality of life using the evolution of QoLgNMD scoring between the baseline visit, the visit at 6 months and the final visit at 12 months as endpoints
- To evaluate the efficacy of metformin on cardiac function using the evolution of left ventricular ejection fraction between the baseline visit and the final visit at 12 months as endpoints.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
METFORMINE VIATRIS 500 mg, comprimé dispersible
PRD9930710 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- DISPERSIBLE TABLET
- Route of administration
- ORAL
- Max daily dose
- 3000 mg milligram(s)
- Max total dose
- 1095 g gram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- NL 32726
- MA holder
- VIATRIS SANTE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Assistance Publique Hopitaux De Paris
- Sponsor organisation
- Assistance Publique Hopitaux De Paris
- Address
- Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
- City
- Paris Cedex 10
- Postcode
- 75475
- Country
- France
Scientific contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Pr Pascal LAFORET
Public contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Malika Yahmi
Locations
1 EU/EEA country · 15 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 203 | 15 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Universitaire De Toulouse
Centre de Référence des Maladies Neuromusculaires, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
CHRU De Nancy
Centre de Référence des Maladies Neuromusculaires, Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Nancy Cedex
Centre Hospitalier Universitaire De Lille
Centre de Référence des Maladies Neuromusculaires, Avenue Du Professeur Emile Laine, 59037, Lille Cedex
Assistance Publique Hopitaux De Paris
Centre de Référence des Maladies Neuromusculaires, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex
Les Hopitaux Universitaires De Strasbourg
Centre de Référence des Maladies Neuromusculaires, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Centre Hospitalier Regional Et Universitaire De Brest
Centre de Référence des Maladies Neuromusculaires, Boulevard Tanguy Prigent, 29609, Brest Cedex 2
Assistance Publique Hopitaux De Paris
Centre de Référence des Maladies Neuromusculaires, 43 Boulevard De L Hopital, 75013, Paris
Centre Hospitalier Universitaire De Nantes
Centre de Référence des Maladies Neuromusculaires, 1 Place Alexis Ricordeau, 44000, Nantes
Assistance Publique Hopitaux De Paris
Centre de référence des maladies neuromusculaires, 104 Boulevard Raymond Poincare, 92380, Garches
Centre Hospitalier Universitaire De Bordeaux
Centre de Référence des Maladies Neuromusculaires, 1 Rue Jean Burguet, 33000, Bordeaux
Centre Hospitalier Et Universitaire De Limoges
Centre de Référence des Maladies Neuromusculaires, 2 Avenue Martin Luther King, 87042, Limoges Cedex 1
Centre Hospitalier Universitaire De Montpellier
Centre de Référence des Maladies Neuromusculaires, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Centre Hospitalier Universitaire D'Angers
Centre de Référence des Maladies Neuromusculaires, 4 Rue Larrey, 49100, Angers
Centre Hospitalier Universitaire De Nice
Centre de Référence des Maladies Neuromusculaires, 30 Voie Romaine, 06000, Nice
Hospices Civils De Lyon
Centre de Référence des Maladies Neuromusculaires, 59 Boulevard Pinel, 69500, Bron
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-12-03 | 2024-12-03 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol _2023-507660-39-00 | 2-2 |
| Protocol (for publication) | D4_Investigator list_2023-507660-39-00 | 2-0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire 2023-507660-39-00 | 1 |
| Protocol (for publication) | D4_Patient facing documents_carnet patient_2023-507660-39-00_J1-M3 | 1 |
| Protocol (for publication) | D4_Patient facing documents_carnet patient_2023-507660-39-00_M3-M6 | 1 |
| Protocol (for publication) | D4_Patient facing documents_carnet patient_2023-507660-39-00_M6-M12 | 1 |
| Protocol (for publication) | D4_Patient facing documents_Patient Card _2023-507660-39-00 | 1-1 |
| Protocol (for publication) | D4_Pregnancy_notification_form_2023-507660-39-00 | 1 |
| Protocol (for publication) | D4_SAEnotification_form _2023-507660-39-00 | 1 |
| Recruitment arrangements (for publication) | RecruitmentProcedure_2023-507660-39-00 | 1-1 |
| Subject information and informed consent form (for publication) | L1_SIS _2023-507660-39-00 | 2-1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPCMETFORMINE | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_FR_2023-507660-39-00 | 2-2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-19 | France | Acceptable 2024-06-20
|
2024-06-24 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-04-30 | France | Acceptable 2025-08-04
|
2025-08-07 |