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

• Proportion of at least 5% reduction in weight [ Time Frame: 24 weeks ]
  Determine the proportion of at least 5% reduction in weight compared with baseline weight at week 24
  
  

• Proportion of subjects achieving at least 5% reduction in weight compared with baseline [ Time Frame: 52 weeks ]
  Proportion of subjects achieving at least 5% reduction in weight at 52 weeks
  
  
• Changes in waist circumference at weeks 24 and 52 compared with baseline [ Time Frame: 24 week and 52 week ]
  Compare the change in waist circumference between different treatment arms
  
  
• At least 5% decrease in waist to hip ratio [ Time Frame: 24 week and 52 week ]
  Compare the change in waist to hip ratio between different treatment arms
  
  
• At least 5% decrease in total body weight [ Time Frame: 24 week and 52 week ]
  Compare the change in total body weight between different treatment arms
  
  
• Changes in body weight to calculate body mass index (BMI) at weeks 24 and 52 compared with baseline [ Time Frame: 24 week and 52 week ]
  Compare the change in weight to calculate the BMI between different treatment arms
  
  
• Changes in liver biochemistry [ Time Frame: 24 week and 52 week ]
  Compare the change in liver biochemistry between different treatment arms at weeks 24 and 52 compared with baseline
  
  
• Changes in fasting glucose [ Time Frame: 24 week and 52 week ]
  Compare the change in fasting glucose between different treatment arms at weeks 24 and 52 compared with baseline
  
  
• Changes in fasting lipids [ Time Frame: 24 week and 52 week ]
  Compare the change in fasting lipids between different treatment arms at weeks 24 and 52 compared with baseline
  
  
• Changes in fasting insulin [ Time Frame: 24 week and 52 week ]
  Compare the change in fasting insulin between different treatment arms at weeks 24 and 52 compared with baseline
  
  
• Changes in HbA1c [ Time Frame: 24 week and 52 week ]
  Compare the change in HbA1C between different treatment arms at weeks 24 and 52 compared with baseline
  
  
• A 30% decrease in insulin resistance at weeks 24 compared with baseline [ Time Frame: 24 week ]
  Compare the change in insulin resistance between different treatment arms
  
  
• Changes in liver stiffness to assess improvement of other metabolic disease weeks 24 compared with baseline [ Time Frame: 24 week ]
  Compare the change in liver stiffness between different treatment arms
  
  
• Change in microbiome of stool before reverting to baseline [ Time Frame: weeks 4, 8, 12, 16, 20, 24 and 52 ]
  Compare the change in microbiome between different treatment arms
  
  
• Duration of stool microbiome change before reverting to baseline [ Time Frame: weeks 4, 8, 12, 16, 20, 24 and 52 ]
  Duration of stool microbiome between different treatment arms
  
  

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. In China, more than 100 million people are estimated to suffer from diabetes. Similarly, the prevalence of overweight and obese individuals in China has increased by four-fold from 3.7% to 19.0% over two decades 1. 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.

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. Furthermore, clinical trials are being conducted to evaluate its use for other conditions including inflammatory bowel disease, irritable bowel syndrome, diabetes mellitus, non-alcoholic steatohepatitis and hepatic encephalopathy. 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.