Clinical trial NCT03127696: Randomised Placebo-controlled Study of FMT to Impact Body Weight and Glycemic Control in Obese Subjects With T2DM
Official title: A Randomised Placebo-controlled Study of Fecal Microbiota Transplant (FMT) to Impact Body Weight and Glycemic Control in Obese Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type2 Diabetes
Type 2 Diabetes Mellitus
Obese
Keywords: Fecal Microbiota Transplant
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2017-04-25
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: 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
timeFrame: 24 weeks
Secondary outcomes:
measure: Changes in microbial composition (including bacteriome and virome), function and metabolite
timeFrame: 4, 16, 20, 24 week
measure: Changes in microbiome of stool (including bacteriome and virome)
timeFrame: 4, 16, 24 week
measure: Difference in microbiome (including bacteriome and virome) compared between subjects in different treatment arm
timeFrame: 24 week and 52 week
measure: Proportion of microbiome (including bacteriome and virome) derived from recipient, donor or both in subjects who received FMT
timeFrame: weeks 4, 8, 12, 16, 20, 24 and 52
measure: Difference in microbiome (including bacteriome and virome) compared between subjects who have weight loss and those do not have weight loss
timeFrame: weeks 4, 8, 12, 16, 20, 24 and 52
measure: Microbial factors (including bacteriome and virome) that are associated with percentage of body weight loss
timeFrame: weeks 4, 8, 12, 16, 20, 24 and 52
measure: Trans-kingdom correlation of microbial engraftment
timeFrame: weeks 4, 8, 12, 16, 20, 24 and 52
measure: Proportion of subjects with serious adverse events compared between treatment arm, especially those related to FMT
timeFrame: weeks 4, 8, 12, 16, 20, 24 and 52
measure: Explore changes in fungome microbiota
timeFrame: weeks 4, 8, 12, 16, 20, 24 and 52
measure: Proportion of subjects achieving at least 10% reduction in weight compared with baseline
timeFrame: 52 weeks
measure: Proportion of subjects achieving at least 10% reduction in weight compared with baseline
timeFrame: 24 weeks
measure: Changes in body weight to calculate body mass index (BMI) at weeks 24 and 52 compared with baseline
timeFrame: 24 week and 52 week
measure: Changes in biochemical parameters
timeFrame: 24 week and 52 week
measure: A 30% decrease in insulin resistance at weeks 24 compared with baseline
timeFrame: week 24
measure: Changes in liver stiffness to assess improvement of other metabolic disease weeks 24 compared with baseline
timeFrame: week 24
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Siew NG, Prof.
role: PRINCIPAL_INVESTIGATOR
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