Fecal Microbiota Transfer to Improve Diabetes Control Post-bariatric Surgery
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Hba1c change from baseline to 6 months post randomization
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1
FMT (from healthy lean euglycemic non-obese donors)
干预措施: Capsulized fecal microbiota transfer containing the healthy feces + stool dilution solution (Drug)
2
Placebo of FMT
干预措施: Capsulized placebo transfer containing dilution solution (Drug)
结局指标
主要结局
Hba1c change from baseline to 6 months post randomization
时间窗: At baseline and at 6 months after randomization
次要结局
- 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)
- Evaluate FMT safety(From baseline to 2 years post-randomization)
- Evaluate quality of life(At baseline and at 6 weeks, 12 weeks, 18 weeks, 24 weeks, 1 year and 2 years post randomization)
- Evolution of insulin secretion from baseline to 24 weeks using the HOMA-B calculator(At baseline and at 24 weeks post-randomization)
- Number of anti-diabetic (antiT2D) drugs(At baseline and at 1 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)
- Evolution of insulin resistance from baseline to 24 weeks(At baseline and at 24 weeks post-randomization)
- 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)