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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003841-13 | EudraCT Number |
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Obesity progresses worldwide with few effective treatments leading to a burst in Bariatric surgery (BS). France is the 3rd country in BS numbers yearly.
BS improves diabetes (T2D) and even induces diabetes remission (DR) in 60% of patients. Thus, an expert consensus recommended extending BS to T2D with BMI≥30kg/m² with uncontrolled glycaemia, anticipating even more BS. Glycaemic control further deteriorates in the longer term in non DR (NDR) patients and relapse occurs in some DR patients, urging the need to add new therapy to control glycaemia and provide new recommendations in the future.
Obesity and T2D are characterized by gut microbiota dysbiosis with low to very low microbial gene richness (MGR). About 75% of patients' candidates for BS are in the low MGR category. Whereas BS modifies microbiota composition and increases MGR 1-year post-BS, we demonstrated that only a few patients reach high MGR. Dysbiosis can be improved by several means; fibre enriched diet, prebiotics, probiotics also improve metabolic alterations and insulin resistance in mice. However, human studies observed rather divergent results: some studies display a beneficial effect in improving insulin-resistance but to a small extent while others do not display any significant effects at all. Therefore, other innovative strategies should be tested in humans. For example, Faecal microbiota transfer (FMT) ameliorates insulin sensitivity and MGR in metabolic syndrome patients, but was never tested in T2D nor post-BS. Whether adding such an innovative therapy to further modify gut microbiota post-BS can help improve glucose control should be tested.
FMT showed health benefits in several diseases (clostridium difficile (CD) and Crohn's). Until recently, FMT was performed using invasive tool (endoscopy or colonoscopy) thus with potential secondary effects, or enema yet maybe less effective. Recent technologic developments enabled to generate oral capsulized FMT (filled with fecal material) performing as well as invasive FMT for CD with good tolerance. This strategy has never been tested in obesity or T2D, whereas in metabolic syndrome patients (before T2D occurrence) and less severe dysbiosis, a proof-of-concept study showed that endoscopic FMT may improve insulin sensitivity after 6 weeks. Yet these studies have included a small number of patients, non T2D and did not test oral FMT. We here hypothesize that an intervention improving dysbiosis after 1-year post-BS might help improve/maintain diabetes control in the long-term. We will examine the effects of FMT (from lean healthy donors) vs. placebo transfer in dietary-controlled non-DR patients after 1-year post-BS, on Hba1c reduction evaluated 6 months' post-intervention
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | FMT (from healthy lean euglycemic non-obese donors) |
|
| 2 | Placebo Comparator | Placebo of FMT |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capsulized fecal microbiota transfer containing the healthy feces + stool dilution solution | Drug | 1 FMT=30 capsulized FMT given during 2 days in several intakes per day (3 intakes per day). FMT will be performed at baseline after randomization. Further treatment(s) will be given again at 6 and 12 weeks if we do not observe a change of Hba1c of at least -0.15% in patients who have Hba1c at inclusion <7%; of at least -0.4% in patients who have Hba1c at inclusion ≤8% and of at least -0.7% in patients who have Hba1c at inclusion >8%. |
| Measure | Description | Time Frame |
|---|---|---|
| Hba1c change from baseline to 6 months post randomization | At baseline and at 6 months after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Evolution of Hba1c from baseline to 2 years post-randomization | At baseline and at 6 weeks, 12 weeks, 18 weeks, 24 weeks, 1 year and 2 years post randomization | |
| Evolution of C-peptide from baseline to 2 years post-randomization | At baseline and at 6 weeks, 12 weeks, 18 weeks, 24 weeks, 1 year and 2 years post randomization |
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Inclusion Criteria patients :
Exclusion Criteria patients :
Inclusion criteria donors:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Judith Aron-Wisnewsky, Pr | Contact | +33 1 42 17 75 41 | judith.aron-wisnewsky@aphp.fr | |
| Karine Clement, Pr | Contact | +33 1 42 17 79 28 | karine.clement@aphp.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Groupe hospitalier Pitié-Salpêtrière | Recruiting | Paris | 75013 | France |
The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations
Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
Researchers who provide a methodologically sound proposal.
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| Capsulized placebo transfer containing dilution solution | Drug | 1 Placebo of FMT=30 capsulized given during 2 days in several intakes per day (3 intakes per day). Placebo of FMT will be performed at baseline after randomization. Further treatment(s) will be given again at 6 and 12 weeks if we do not observe a change of Hba1c of at least -0.15% in patients who have Hba1c at inclusion <7%; of at least -0.4% in patients who have Hba1c at inclusion ≤8% and of at least -0.7% in patients who have Hba1c at inclusion >8%. |
|
| Evolution of insulin secretion from baseline to 24 weeks using the HOMA-B calculator | Equal to 20 x fasting insulin (μIU/ml)/ fasting glucose (mmol/ml) - 3.5 | At baseline and at 24 weeks post-randomization |
| Evolution of insulin resistance from baseline to 24 weeks | we will use the HOMA-IR (= fasting insulin (μIU/ml) × fasting glucose (mmol/ml)/ 22.5) and Disse index (=Disse 12*((2.5*(HDL-total cholesterol)-NEFA)-insulin)) which are two complementary markers to evaluate insulin resistance using different parameters | At baseline and at 24 weeks post-randomization |
| Glycaemia profile (using glycemic holter) changes from baseline to 6 weeks and 24 weeks | Glycemic holter will be placed on the patient for 3 days at baseline, 6 weeks and 6 months and will collect glycemic curve excursions that will further be compared at the different visits (baseline, 6 and 24 weeks). We will analyse the % and duration of hyperglycemia and hypoglycaemia and the % of time and duration at glycemic target at the different visits (baseline, 6 and 24 weeks) | At baseline and at 6 weeks and 24 weeks post-randomization |
| Number of anti-diabetic (antiT2D) drugs | The number of concomitant anti-diabetic drugs will be analysed | At baseline and at 1 and 2 years post-randomization |
| Type of antiT2D drugs | The type of anti-diabetic drugs will be analysed | At baseline and at 1 and 2 years post-randomization |
| Number of patients reaching Diabetic Remission (DR) | At baseline and at 24 weeks, 1 and 2 years post-randomization |
| Proportion of patient needing a "safety" glucose lowering treatment to control Hba1c despite FMTs (or placebo) | From baseline to 2 years post-randomization |
| Evaluate FMT safety | Evaluate safety and AE by a systematic screening regarding fever, bloating, diarrhoea, regurgitation at each visit | From baseline to 2 years post-randomization |
| Evaluate quality of life | Evaluate changes in quality of life after capsulized FMT (baseline vs. after FMT and between treatment groups using SF36 questionnaire) | At baseline and at 6 weeks, 12 weeks, 18 weeks, 24 weeks, 1 year and 2 years post randomization |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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