Randomised Placebo-controlled Study of FMT to Impact Body Weight and Glycemic Control in Obese Subjects With T2DM

Not Applicable

Completed

• Conditions: Type 2 Diabetes Mellitus; Obese; Type2 Diabetes
• Interventions: Procedure: Fecal Microbiota Transplantation; Behavioral: Lifestyle Modification Program; Procedure: Sham

• Registration Number: NCT03127696
• Lead Sponsor: Chinese University of Hong Kong

Brief Summary

Faecal microbiota transplantation (FMT) represents a clinically feasible way to restore the gut microbial ecology, and has proven to be a breakthrough for the treatment of recurrent Clostridium difficile infection. Early results in human have shown that FMT from lean donor when transplanted into subjects with metabolic syndrome resulted in a significant improvement in insulin sensitivity and an increased in intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. The therapy is generally well tolerated and appeared safe. No clinical studies have assessed the efficacy of FMT in obese subjects with type 2 diabetes mellitus.

Detailed Description

There is a worldwide epidemic of obesity and type 2 diabetes mellitus. The prevalence of obesity and type 2 diabetes mellitus continues to rise at an alarming rate. Weight loss is associated with reductions in risk of morbidity and mortality from obesity. Conventional non-pharmacological interventions based on diet and exercise showed limited long-term success in producing sustained weight loss. Although obese patients with type 2 diabetes mellitus may be treated by medications or by bariatric surgery, these alternatives are limited by incomplete resolution of the diseases, high cost or potential surgical-related morbidity. Further research focusing on increasing effectiveness of interventions and new ways to achieve weight loss in these individuals are needed.

Recently, accumulating evidence supports a role of the enteric microbiota in the pathogenesis of obesity-related insulin resistance. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome appears to be more efficient in harvesting energy from the diet. Colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota', suggesting gut microbiota as an additional contributing factor to the pathophysiology of obesity. Obese and lean phenotypes can also be induced in germ-free mice by transfer of fecal microbiota from human donors. These data have led to the use of microbiota therapeutics as a potential treatment for metabolic syndrome and obesity.

Clinical trials are being conducted to evaluate its use for other conditions. Early results in human have shown that FMT from lean donor when transplanted into subjects with metabolic syndrome resulted in a significant improvement in insulin sensitivity and an increased in intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. The therapy is generally well tolerated and appeared safe. No clinical studies have assessed the efficacy of FMT in obese subjects with type 2 diabetes mellitus.

No clinical studies have assessed the efficacy of FMT in obese subjects with type 2 diabetes mellitus.

A subgroup of 30 subjects will be analyzed at week 24. The difference and proportion in microbiome in different arms, microbial factors, and trans-kingdom correlation of microbial engraftment will be correlated with clinical data in an unblinded manner.

Study Timeline

• Study First Submitted: 2017-04-07
• Study First Submitted QC: 2017-04-20
• Study First Posted: 2017-04-25
• Study Start: 2017-04-26
• Primary Completion: 2019-05-15
• Study Completion: 2019-12-06
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-13
• Last Update Posted: 2022-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

• Age 18-70; and
• BMI >=28 kg/m2 and < 45 kg/m2; and
• A diagnosis of Type 2 diabetes mellitus for >=3 months; and
• Written informed consent obtained

Read More

Exclusion Criteria

• Current pregnancy
• Use of any weight loss medications in the preceding 1 year
• Known history or concomitant significant gastrointestinal disorders (including Inflammatory Bowel Disease, current colorectal cancer, current GI infection)
• Known history or concomitant significant food allergies
• Immunosuppressed subjects
• Known history of severe organ failure (including decompensated cirrhosis), inflammatory bowel disease, kidney failure, epilepsy, acquired immunodeficiency syndrome
• Current active sepsis
• Active malignant disease in recent 2 years
• Known contraindications to oesophago-gastro-duodenoscopy (OGD)
• Use of probiotic or antibiotics in recent 3 months

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FMT + LMP	Fecal Microbiota Transplantation	FMT and lifestyle modification program
FMT + LMP	Lifestyle Modification Program	FMT and lifestyle modification program
FMT alone	Fecal Microbiota Transplantation	Fecal Microbiota Transplantation
Sham + LMP	Lifestyle Modification Program	Sham and lifestyle modification program
Sham + LMP	Sham	Sham and lifestyle modification program

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with at least 20% lean-associated microbiota in recipients after FMT compared with subjects receiving lifestyle intervention alone up to week 24	24 weeks	Proportion of subjects with at least 20% lean-associated microbiota in recipients after FMT compared with subjects receiving lifestyle intervention alone up to week 24.

Secondary Outcome Measures

Name	Time	Method
Changes in microbial composition (including bacteriome and virome), function and metabolite	4, 16, 20, 24 week	Changes in microbial composition (including bacteriome and virome), function and metabolite at weeks 4, 16, 20 and 24 compared with baseline
Changes in microbiome of stool (including bacteriome and virome)	4, 16, 24 week	Changes in microbiome of stool (including bacteriome and virome) at weeks 4, 16 and 24 compared with baseline
Difference in microbiome (including bacteriome and virome) compared between subjects in different treatment arm	24 week and 52 week	Compare the difference in microbiome among different treatment arms
Proportion of microbiome (including bacteriome and virome) derived from recipient, donor or both in subjects who received FMT	weeks 4, 8, 12, 16, 20, 24 and 52	Proportion of microbiome (including bacteriome and virome) derived from recipient, donor or both in subjects who received FMT
Difference in microbiome (including bacteriome and virome) compared between subjects who have weight loss and those do not have weight loss	weeks 4, 8, 12, 16, 20, 24 and 52	Difference in microbiome (including bacteriome and virome) compared between subjects who have weight loss and those do not have weight loss
Microbial factors (including bacteriome and virome) that are associated with percentage of body weight loss	weeks 4, 8, 12, 16, 20, 24 and 52	Microbial factors (including bacteriome and virome) that are associated with percentage of body weight loss
Trans-kingdom correlation of microbial engraftment	weeks 4, 8, 12, 16, 20, 24 and 52	Trans-kingdom correlation of microbial engraftment after FMT between bacteriome, and virome
Proportion of subjects with serious adverse events compared between treatment arm, especially those related to FMT	weeks 4, 8, 12, 16, 20, 24 and 52	Proportion of subjects with serious adverse events compared between treatment arm, especially those related to FMT
Explore changes in fungome microbiota	weeks 4, 8, 12, 16, 20, 24 and 52	Explore changes in fungome microbiota
Proportion of subjects achieving at least 10% reduction in weight compared with baseline	24 weeks	Proportion of subjects achieving at least 10% reduction in weight at 24 weeks
Changes in body weight to calculate body mass index (BMI) at weeks 24 and 52 compared with baseline	24 week and 52 week	Compare the change in weight to calculate the BMI among different treatment arms
Changes in biochemical parameters	24 week and 52 week	Changes in liver biochemistry, fasting glucose, fasting lipids, fasting insulin, HbA1C at weeks 24 and 52 compared with baseline
A 30% decrease in insulin resistance at weeks 24 compared with baseline	week 24	A 30% decrease in insulin resistance at weeks 24 compared with baseline
Changes in liver stiffness to assess improvement of other metabolic disease weeks 24 compared with baseline	week 24	Changes in liver stiffness to assess improvement of other metabolic disease weeks 24 compared with baseline

Trial Locations

Locations (1)

The Chinese University of Hong Kong; 🇭🇰 Sha Tin, Hong Kong