E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes complete remission after Bariatric surgery under antidiabetic drug |
Rémission complète du Diabète de type 2 avec traitement antidiabétique, après chirurgie Bariatrique des |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 Diabetes complete remission after Bariatric surgery under antidiabetic drug |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
Démontrer que la metformine augmente la proportion de patients en rémission du DT2 après 3 ans de traitement comparativement à une prise en charge standard sans traitement médicamenteux, chez des patients anciennement diabétiques de type 2 et opérés de chirurgie bariatrique. |
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E.2.2 | Secondary objectives of the trial |
- 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
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- Évaluer la proportion de patients en rémission partielle ou complète du DT2 après 1 et 2 ans de traitement par metformine comparativement à une prise en charge standard sans traitement médicamenteux. - Évaluer la perte de poids et les paramètres du syndrome métabolique dans le groupe metformine versus prise en charge standard - Évaluer la tolérance, le statut nutritionnel et la compliance au traitement par metformine - Évaluer la microangiopathie et macroangiopathie diabétique à 3 ans dans les deux groupes - Évaluer les modifications de la qualité de vie à 1, 2 et 3 ans - Évaluer l’efficacité du score de prédiction de rémission du diabète long terme (c’est-à-dire la rémission prolongée évaluée à la fin de l’étude avec le score Ad-DiaRem) - Explorer les différences de variation du microbiote intestinal entre chez les patients traités par metformine versus les patients sans traitement
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adults 18-70 years-old - Having undergone gastric bypass or sleeve gastrectomy 12 to 24 months before inclusion - “ex-T2D” treated with at least one anti-diabetic drug before bariatric surgery - HbA1C < 6.5 % at inclusion with no anti-hyperglycemic medications for the last three months - Written consent |
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E.4 | Principal exclusion criteria |
- 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) o Acute or chronic disease which could lead to a tissue hypoxia (ex : cardiac insufficiency, respiratory insufficiency, latest myocardial infarction, shock) o Hepatocellular insufficiency 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
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E.5 End points |
E.5.1 | Primary end point(s) |
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).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- 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 - 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
one with medication, control arm without medication |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 17 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |