Fecal Microbiota Transfer to Improve Diabetes Control Post-bariatric Surgery

Phase 3

Not yet recruiting

• Conditions: Type 2 Diabetes; Bariatric Surgery
• Interventions: Drug: Capsulized fecal microbiota transfer containing the healthy feces + stool dilution solution; Drug: Capsulized placebo transfer containing dilution solution

• Registration Number: NCT06192693
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-12
• Study First Submitted: 2023-12-21
• Study First Submitted QC: 2023-12-21
• Last Update Submitted: 2023-12-21
• Study Start: 2024-01
• Study First Posted: 2024-01-05
• Last Update Posted: 2024-01-05
• Primary Completion: 2029-02
• Study Completion: 2029-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Capsulized fecal microbiota transfer containing the healthy feces + stool dilution solution	FMT (from healthy lean euglycemic non-obese donors)
2	Capsulized placebo transfer containing dilution solution	Placebo of FMT

Primary Outcome Measures

Name	Time	Method
Hba1c change from baseline to 6 months post randomization	At baseline and at 6 months after randomization

Secondary Outcome Measures

Name	Time	Method
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
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
Type of antiT2D drugs	At baseline and at 1 and 2 years post-randomization	The type of anti-diabetic drugs will be analysed
Evaluate FMT safety	From baseline to 2 years post-randomization	Evaluate safety and AE by a systematic screening regarding fever, bloating, diarrhoea, regurgitation at each visit
Evaluate quality of life	At baseline and at 6 weeks, 12 weeks, 18 weeks, 24 weeks, 1 year and 2 years post randomization	Evaluate changes in quality of life after capsulized FMT (baseline vs. after FMT and between treatment groups using SF36 questionnaire)
Evolution of insulin secretion from baseline to 24 weeks using the HOMA-B calculator	At baseline and at 24 weeks post-randomization	Equal to 20 x fasting insulin (μIU/ml)/ fasting glucose (mmol/ml) - 3.5
Number of anti-diabetic (antiT2D) drugs	At baseline and at 1 and 2 years post-randomization	The number of concomitant anti-diabetic drugs will be analysed
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
Evolution of insulin resistance from baseline to 24 weeks	At baseline and at 24 weeks post-randomization	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
Glycaemia profile (using glycemic holter) changes from baseline to 6 weeks and 24 weeks	At baseline and at 6 weeks and 24 weeks post-randomization	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)

Trial Locations

Locations (1)

Groupe hospitalier Pitié-Salpêtrière; 🇫🇷 Paris, France