Impact of Metformin on Peripheral Arterial Calcification in Type 1 Diabetes

Overview

Sponsor-declared trial summary

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] - Nutritional and Metabolic Diseases [C18]

Trial duration

2 Jun 2021 → ongoing

Decision date (initial)

2024-09-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Organisation name Direction Générale de l’Offre des Soins du Ministère de la santé et de la prévent

External identifiers

EU CT number

2024-511867-27-00

EudraCT number

2018-003121-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To show that metformin, patients with type 1 diabetes but without chronic kidney disease, is able to slow below- knee arterial calcification

Secondary objectives 5

1. To show that metformin, in patients with type 1 diabetes but without CKD, is able to slow below-knee arterial occlusive disease
2. To show that metformin, in patients with type 1 diabetes but without CKD, is able to improve ankle and toe brachial indexes
3. To show that metformin, in patients with type 1 diabetes but without CKD, is able to improve pulse wave velocity
4. To show that metformin, in patients with type 1 diabetes but without chronic kidney disease, is able to slow coronary arterial calcification
5. To conduct a subgroup analysis for the primary outcome to evaluate whether the effect of metformin on the difference of below-knee arterial calcification score evaluated by CT-scan at T0 and T2years varies according to initial below-knee arterial calcification score (≤ versus >400).

Conditions and MedDRA coding

Vascular calcification and type 1 diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Type 1 diabetes
2. Women and Men ≥ 18 years old and ≤ 80 years old with: *Complications: -diabetic retinopathy and/or -nephropathy (with creatinine clearance ≥ 60 mL/mn) and/or -neuropathy and/or -peripheral arterial occlusive disease and/or -cardiopathy and/or -stroke and/or *cardiovascular risk factors - hypertension and/or - dyslipidemia (HDL < 0.35g/L or LDL > 1.9g/L or treated dyslipidemia) and/or - tobacco use (old or active smoking greater than 5 pack years) and/or *Diabetes duration >20 years
3. For women in childbearing age, effective contraception during the whole trial
4. Signed written informed consent
5. Affiliation of a social security regime (patient with AME cannot be included)

Exclusion criteria 11

1. Creatinine clearance of less than 3 months <60 mL/mn (MDRD) at the inclusion time
2. Known metformin contra-indication: • severe liver insufficiency –CHILD B or C • heart failure (FEVG<45%) or • history of pulmonary oedema, respiratory insufficiency with history of acute respiratory failure or patients receiving oxygen therapy • chronic ethylism • lactic acidosis
3. Known hypersensitivity to metformin or to any of its excipients or placebo excipients (lactose)
4. Indication or history of lower limb angioplasty (with stenting) and/or bypass
5. Previous treatment with metformin (within 3 months prior to inclusion)
6. HbA1c of less than 3 months >11%
7. Chronic inflammatory disease or chronic immune-suppressive drugs intake
8. Participation in an another interventional trial (Jardé 1 and 2) or in the exclusion period of any other interventional study
9. Pregnancy woman (confirmed by a sanguine beta-HCG test) or breastfeeding woman
10. Patient under legal protection measure (tutorship or curatorship) or deprived of freedom or under measure of safety
11. Unable to consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference between below-knee arterial calcification score evaluated by CT-scan at T0 and T2years in type 1 diabetic patients treated or not with metformin.

Secondary endpoints 5

1. Difference between below-knee arterial ultrasonographic occlusion score at T0 and T2years in type 1 diabetic patients supplemented or not with metformin.
2. Difference between ankle and toe brachial indexes at T0 and T2years in type 1 diabetic patients supplemented or not with metformin.
3. Difference between pulse wave velocity at T0 and T2 years in type 1 diabetic patients supplemented or not with metformin.
4. Difference between coronary calcification score evaluated by CT-scan at T0 and T2years in type 1 diabetic patients treated or not with metformin.
5. Difference between below-knee arterial calcification score progression between T0 and T2years in type 1 diabetic patients treated or not with metformin and with initial below-knee arterial calcification score ≤ and >400.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

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

Coordinating Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications