Study comparing a metformin treatment to standard care to extend time without diabetes after bariatric surgery

Start 7 Jan 2021 · Status Ongoing, recruiting · 1 EU/EEA countries · 13 sites · Protocol P170901J

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ongoing, recruiting

Participants planned 126

Countries 1

Sites 13

Type 2 Diabetes complete remission after bariatric surgery under antidiabetic drug

To demonstrate that metformin increases the proportion of patients with T2D remission compared to standard care among ex-T2D patients operated of BS, after a 3-year period of treatment.

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: 7 Jan 2021 → ongoing
Decision date (initial): 2024-08-14
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: French Ministry of Health: Programme hospitalier de Recherche Clinique – PHRC 2017

External identifiers

EU CT number: 2024-516409-22-00
EudraCT number: 2019-000312-28
ClinicalTrials.gov: NCT04581447

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate that metformin increases the proportion of patients with T2D remission compared to standard care among ex-T2D patients operated of BS, after a 3-year period of treatment.

Secondary objectives 7

To assess the proportion of patients with T2D partial or complete remission with metformin compared to standard care in ex-T2D patients operated of BS, after 1 and 2 years of treatment
To assess body weight and metabolic parameters in metformin group versus standard care.
To assess tolerance, nutritional status and adherence to metformin in intervention group versus standard care.
To assess micro and macroangiopathy at 3 years.
To assess quality of life changes from baseline at 1, 2 and 3 years.
To assess the accuracy of long term prediction score (i.e. prolonged remission assessed at the end of the study with the Ad-DiaRem score)
To explore gut microbiota differences (diversity, composition and function) between metformin treated and non-treated individuals

Conditions and MedDRA coding

Type 2 Diabetes complete remission after bariatric surgery under antidiabetic drug

Version	Level	Code	Term	System organ class
20.0	LLT	10012594	Diabetes	10027433
20.0	SOC	10014698	Endocrine disorders	5

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

Adults 18-70 years-old
Having undergone gastric bypass or sleeve gastrectomy 12 to 36 ±3 months before inclusion
Ex-T2D treated with at least one anti-diabetic drug before bariatric surgery or HbA1c ≥ 6.5% before bariatric surgery
HbA1C < 6.5 % at inclusion with no anti-hyperglycemic medications for the last three months
Written consent

Exclusion criteria 7

Known type 1 diabetes
Pregnancy and breastfeeding
Estimated glomerular filtration rate ≤44 ml/min (MDRD)
Known intolerance to metformin
Known contraindication to metformin: o Acute metabolic acidosis o Acute affection which could lead to renal deterioration (ex: dehydration, serious infection, shock, intravascular administration of iodinated contrast agent within the last 48 hours) o Acute or chronic disease which could lead to a tissue hypoxia (ex : severe cardiac insufficiency, severe respiratory insufficiency, myocardial infarction within the last 3 months, shock) o Hepatocellular insufficiency o Prothrombin ratio ≤ 50% o SGOT or SGPT levels ≥ 10 times the upper limits of the normal range o Alcohol use disorder
Medications and medical conditions likely to confound the assessment of diabetes: o glucocorticoids treatment o renal graft o Cushing’s syndrome o acromegaly o fasting plasma triglyceride > 600 mg/dl despite treatment
Patient under legal protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Proportion of patients with partial or complete T2D remission criteria at three years in T2D patients operated of BS (GB or SG). Criteria for diabetes remission assessment will be used as described in 2012 in the American Diabetes Association guidelines (8,9): - Complete remission: HbA1c<5.7% and no anti-diabetic medication (except metformin in the experimental group). - Partial remission: HbA1c<6.5% and no anti-diabetic medication (except metformin in the experimental group).

Secondary endpoints 11

Proportion of patients with T2D partial or complete remission criteria at 1 and 2 years
Proportion of patients with strict complete remission at 3 years
Percentage of weight and BMI change at 1,2 and 3 years compared to baseline
Level of cardio-metabolic parameters associated to T2D (fasting glycaemia and insulinemia, HOMA-IR, triglycerides and HDL cholesterol, blood pressure) at 1,2 and 3 years compared to baseline
Level of nutritional parameters associated with BS (albumin, hemoglobin, iron, serum ferritin, transferrin saturation, calcium, vitamins D and B1, B9, B12) at 1,2 and 3 years compared to baseline
Proportion of adverse drug reactions in the intervention group compared to standard care all along the trial (all visits)
Adherence level in the intervention group as measured using pill counts (defined as taking at least 80% of assigned study pills in the intervention group) (all visits) and metformin plasmatic dosage at 1,2 and 3 years in sites that can perform it
Number and level of retinopathy, nephropathy and macroangiopathy events at 3 years
Quality of life changes assessed by EQ5D auto-questionnaire from baseline to 1, 2 and 3 years
5y-Ad-Diarem score calculated with baseline data (inclusion) to assess clinical outcome at the end of the study
Changes in fecal microbiota (diversity, composition and function) from baseline at 1 and 3 years

Investigational products

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

Test 1

Metformin Embonate

SCP10310250 · ATC

Active substance: Metformin Embonate
Substance synonyms: Metformin hemiembonate, METFORMIN PAMOATE
Route of administration: ORAL USE
Max daily dose: 1700 mg milligram(s)
Max total dose: 1836 g gram(s)
Max treatment duration: 36 Month(s)
Authorisation status: Authorised
ATC code: A10BA02 — METFORMIN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: 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 Claire CARETTE

Public contact point

Organisation: Assistance Publique Hopitaux De Paris
Contact name: Pr Claire CARETTE

Locations

1 EU/EEA country · 13 investigational sites

By country

Country	MS status	Planned subjects	Sites
France	Ongoing, recruiting	126	13
Rest of world	—	0	—

Investigational sites

France

13 sites · Ongoing, recruiting

Centre Hospitalier Universitaire De Lille

Chirurgie Générale et Endocrinienne, Rue Michel Polonovski, 59037, Lille Cedex

Centre Hospitalier Universitaire De Toulouse

Endocrinologie, maladies métaboliques et nutrition, 24 Chemin De Pouvourville, 31400, Toulouse

Hospices Civils De Lyon

Service d'endocrinologie, diabétologie, maladies de la nutrition, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite