Randomized Controlled Trial of Fecal Microbiota Transplantation in Severe Obesity
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Obesity, Morbid
- Sponsor
- University Hospital of North Norway
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Change in individual weight loss (kg).
- Status
- Enrolling By Invitation
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a randomized, double-blinded and placebo controlled prospective trial with sixty patients to investigate the effect of fecal microbiota transplantation (FMT) on body weight in patients with severe obesity. We will also collect data that possibly could give a better understanding of mechanisms of this correlation.
Detailed Description
Obesity is a main threat to public health in western countries. This condition increases the risk of developing type 2 diabetes, cardiovascular diseases, physical stress disorders, dispose for cancer and contributes to increased overall morbidity and mortality. However sustained weight loss lead to the reduction of risk factors and improvement of several obesity related co-morbidities. Currently there are mainly two established treatments for severe obesity: a conservative approach through lifestyle intervention and a surgical approach with bariatric surgery. The gut microbiota is recognized as an environmental modulator of nutritional uptake and body weight. This has led to the hypothesis that the gut microbiota could be a therapeutic target fighting obesity. Fecal microbiota transplantation (FMT) has been applied for more than 50 years, and is a established treatment for refractory recurrent infection with Clostridium Difficile (CDI). Recent scientific studies have also applied FMT as treatment for other diseases like inflammatory bowel disease, irritable bowel disease and even metabolic syndrome and the results are promising. The sample size is determined based on data from the outpatient clinic at UNN Harstad medical department. Patients here have an average weight loss of 2,5 % with conservative treatment. This will therefore be the expected result in the control group (receiving placebo). A weight reduction of 5-10% leads to significant improvement of health and quality of life, and a weight change of this magnitude is therefore the hypothesis. The difference between the two groups is estimated to 7,5 %. With these historical results, the sample size is estimated to be 19 patients in each group. Extreme values will be eliminated; more than 3 SD out of the average in the group. In this patient group, we must also be prepared to high degree loss of follow-up near one third, which is also the experience from the clinic. We will include totally 60 patients, 30 in each group. The investigators are planning a randomized, double-blinded and placebo controlled prospective trial with sixty patients to investigate the effect of fecal microbiota transplantation (FMT) on body weight in patients with severe obesity. In the trial there will also be collected data that possibly could give a better understanding of mechanisms of this correlation; with insulin resistance, blood pressure, complete body scan, inflammation and biochemical parameters of hepatic steatosis, changes in the patients microbiota and the development in quality of life as secondary outcome measures.
Investigators
Eligibility Criteria
Inclusion Criteria
- •BMI \> 40 or BMI \> 35 kg/m2 combined with comorbidity related to obesity.
Exclusion Criteria
- •Symptomatic cardiovascular disease, lung disease, cirrhosis or significant renal failure.
- •Patients who are pregnant or breastfeeding
- •Patients who have a confirmed malignancy or cancer
- •Patients who are immunocompromised
- •Previous gastric or small intestinal surgery that alters gut anatomy such as fundoplication, gastric resection, gastric bypass, small bowel resection, and ileoectomy
- •Established drug- or alcohol abuse or particularly unstable psychosocial circumstances.
- •History of cholecystektomy (gut microbiota composition could be affected by bile acid composition)
- •New drugs the last three months or during the follow-up period that can impact on metabolism or body weight
- •Antibiotic treatment the last three months
Outcomes
Primary Outcomes
Change in individual weight loss (kg).
Time Frame: Change from baseline body weight at 12 months post FMT
Partisipants will be measured at the outpatient clinic, medical department UNN Harstad, and weight in kilograms (kg) will be recorded. The data will be represented both as average weight change and as bar charts with \>10%, with comparison between the intervention and control group. Chi Square or Fischer exact test will be used to present responders and non-responders in the active and controll group. We will use odds ratio to present responders in the active group.
Secondary Outcomes
- Change in individual weight loss (kg)(Change from baseline body weight at 3, 6 and 12 months after FMT)
- Change in waist circumference (cm)(Change from baseline waist circumferense at 3, 6 and 12 months after FMT)
- Changes in HbA1c (mmol/mol)(Change from baseline HbA1c at 3, 6 and 12 months after FMT)
- Changes in fasting glucose (mmol/L)(Change from baseline fasting glucose at 3, 6 and 12 months after FMT)
- Changes in insuline (pmol/L)(Change from baseline insuline at 3, 6 and 12 months after FMT)
- Changes in C-peptide (pmol/L)(Change from baseline C-peptide at 3, 6 and 12 months after FMT)
- Change in blood pressure(Change from baseline blood pressure at 3, 6 and 12 months after FMT)
- Change in sedimentation rate (mm/t)(Change from baseline sedimentation rate at 3, 6 and 12 months after FMT)
- Change in hs-CRP (mg/L)(Change from baseline hs-CRP at 3, 6 and 12 months after FMT)
- Changes in multiplex cytokine panel (pg/mL)(Change from baseline cytokine panel at 3, 6 and 12 months after FMT)
- Changes in biochemical parameters of hepatic steatosis (U/L)(Change from baseline biochemical parameters at 3, 6 and 12 months after FMT)
- Changes in lipid profile based on HDL/LDL (mmol/L) and cholesterol (mmol/L)(Change from baseline lipid profile at 3, 6 and 12 months afterFMT)
- Changes in life quality measured using RAND-36 questionnaire(Change from baseline RAND-36 score 12 months after FMT)
- Changes in psychiatric comorbidity measured by HSCL-25(Change from baseline HSCL-25 score 12 months after FMT)
- Changes in dietary intake measured by FFQ(Change from baseline FFQ score at 3, 6 and 12 months after FMT)
- Changes in life style measured by IPAQ(Change from baseline IPAQ score at 3, 6 and 12 months after FMT)
- Gut microbiota composition and function(Change from baseline microbiota composition at 3, 6 and 12 months after FMT)
- Short difficult childhood questionnaire(At baseling)
- Childhood trauma Questionnaire (CTQ)(Once during the follow up period in the study)
- Heart rate variability (HRV)(HRV will be measured at inclusion and 3.months post FMT)