Fecal Microbiota Transplant (FMT) to Induce Weight Loss in Obese Subjects

Study Overview
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Brief Summary
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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. Fecal 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. The therapy is generally well tolerated and appeared safe. No clinical studies have assessed the dosage of FMT in obese subjects.

Detailed Description
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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. Fecal 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 dosage of FMT in obese subjects.

Official Title
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An Open-label Pilot Study of Fecal Microbiota Transplant (FMT) to Induce Weight Loss in Obese Subjects

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75; and BMI ≥28 kg/m^2 and < 45 kg/m^2; and Written informed consent obtained Exclusion Criteria: Current pregnancy Known history or concomitant significant gastrointestinal disorders (including Inflammatory Bowel Disease, current colorectal cancer) Known history or concomitant significant food allergies Immunosuppressed subjects Known history of severe organ failure (including decompensated cirrhosis), kidney failure, epilepsy, acquired immunodeficiency syndrome Current active sepsis Known contraindications to oesophago-gastro-duodenoscopy (OGD) Use of probiotic or antibiotics in recent 3 months New drugs in the last three months that can impact on metabolism or body weight Previous gastric or small intestinal surgery that alters gut anatomy such as fundoplication, gastric resection, gastric bypass, small bowel resection, ileoectomy, colectomy Patients who have a confirmed current active malignancy or cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplantation<br>FMT infusion | Procedure: Fecal Microbiota Transplantation<br>* FMT infusion (100-200ml) and Mucosal Microbiota Assessment (To assess the fecal and mucosal microbiota before and after FMT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of at least 10% reduction in weight | Determine the proportion of at least 10% reduction in weight compared with baseline weight | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects maintaining weight reduction | Proportion of subjects maintaining at least 10% reduction in weight compared with baseline | 12, 26, 52, 78, 104 weeks | 
| Proportion of subjects maintaining weight reduction | Proportion of subjects maintaining at least 5% reduction in weight compared with baseline | 6,12, 26, 52, 78, 104 weeks | 
| Changes in waist circumference | Changes in waist circumference compared with baseline | 6,12, 26, 52, 78, 104 weeks | 
| Decrease in waist to hip ratio and in total body weight | At least 5% decrease in waist to hip ratio and in total body weight | 6,12, 26, 52, 78, 104 weeks | 
| Change in biochemical parameters | Study samples will collected to characterize which microbiota favors FMT by performing metagenomics of gut microbiome in stool samples | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal Microbiota Transplantation, FMT