Randomized Controlled Trial of Fecal Microbiota Transplantation in Severe Obesity (RCTFMTOb)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obesity, Morbid
• Intervention / Treatment: Other: Fecal microbiota transplantation; Other: Placebo: fecal microbiota transplantation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Troms
    • Harstad, Troms, Norway, 9406
      • University Hospital of North Norway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; Active Comparator. Transplant from Donor A or Donor B, or Donor C or Donore D, one transplant consist of 50-80g of feacal matter.	Other: Fecal microbiota transplantation; The intervention treatment is fecal microbiota transplantation made of frozen donor feces. The FMT is transferred as rectal enema where we use a rectal probe with a balloon to prevent leakage and keep the solution long enough in the colon. The patient will stay on the bench in different positions for 20 minutes. We will encourage the participant to keep the solution in the colon as long as possible and give them four pills of loperamide before the procedure in order to reduce bowel motility.
Placebo Comparator: Placebo; Placebo. Patient will recieve an autologous fecal microbiota transplantation.	Other: Placebo: fecal microbiota transplantation; The placebo group get fecal microbiota transplantation made of their own feces. The FMT is transferred as rectal enema where we use a rectal probe with a balloon to prevent leakage and keep the solution long enough in the colon. The patient will stay on the bench in different positions for 20 minutes. We will encourage the participant to keep the solution in the colon as long as possible and give them four pills of loperamide before the procedure in order to reduce bowel motility.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in individual weight loss (kg).	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.	Change from baseline body weight at 12 months post FMT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in individual weight loss (kg)	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 >5%, >15% and >20% weight loss, with comparison between the intervention and control group at each controll point. 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.	Change from baseline body weight at 3, 6 and 12 months after FMT
Change in waist circumference (cm)	Participants will be measured at the outpatient clinic, medical department UNN Harstad, and waist circumference (cm) will be recorded.	Change from baseline waist circumferense at 3, 6 and 12 months after FMT
Changes in HbA1c (mmol/mol)	Together with C-peptide, fasting glucose and insuline it will be used to research insuline resistance.	Change from baseline HbA1c at 3, 6 and 12 months after FMT
Changes in fasting glucose (mmol/L)	Together with HbA1c, C-peptide, and insuline it will be used to research insuline resistance and calculate HOMA-IR and HOMA-B	Change from baseline fasting glucose at 3, 6 and 12 months after FMT
Changes in insuline (pmol/L)	Together with HbA1c, C-peptide, and fasting glucose it will be used to research insuline resistance and calculate HOMA-IR and HOMA-B	Change from baseline insuline at 3, 6 and 12 months after FMT
Changes in C-peptide (pmol/L)	Together with HbA1c, fasting glucose and insuline it will be used to research insuline resistance.	Change from baseline C-peptide at 3, 6 and 12 months after FMT
Change in blood pressure	Participants blood pressure (mmHg) will be measured at the outpatient clinic, medical department UNN Harstad. Blood pressure is collected as the average of the last two out of three measurements, at the end of 5 min resting period in supine position.	Change from baseline blood pressure at 3, 6 and 12 months after FMT
Change in sedimentation rate (mm/t)	We will measure sedimentation rate, and together with hs-CRP and cytokine panel we will investigate inflamation between the group recieving placebo and the group recieving active transplant.	Change from baseline sedimentation rate at 3, 6 and 12 months after FMT
Change in hs-CRP (mg/L)	We will measure hs-CRP, and together with sedimentation rate and cytokine panel we will investigate inflamation between the group recieving placebo and the group recieving active transplant.	Change from baseline hs-CRP at 3, 6 and 12 months after FMT
Changes in multiplex cytokine panel (pg/mL)	We will run a multiplex cytokinepanel consiting of 27 different cytokines to see if the consentration of blood cytokines changes in participants after active treatment/placebo. The cytokine panel consists of TNF-a, IFN-g, IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17A, MCP-1(MCAF), IP-10, Eotaxin, MIP-1a, MIP-1b, RANTES, G-CSF, GM-CSF, Basic FGF, PDGF-BB, VEGF.	Change from baseline cytokine panel at 3, 6 and 12 months after FMT
Changes in biochemical parameters of hepatic steatosis (U/L)	Photometric analysis. We will measue AST, ALT, ALP, ɣGT and amylase to look at changes in biochemical parameters of hepatic steatosis between the group recieving placebo and the group recieving active transplant	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)	Photometric analysis. Changes in cholesterol and HDL/LDL be used to look at changes in lipid profile between the group recieving placebo and the group recieving active transplant	Change from baseline lipid profile at 3, 6 and 12 months afterFMT
Changes in life quality measured using RAND-36 questionnaire	RAND-36- Item Short Form Health Survey. The SF-36 consists of eight scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. By an independent sample T-test (or, if necessary, non-parametric Mann-Whitney) we will compare change in global score. We will apply last value forward for missing values	Change from baseline RAND-36 score 12 months after FMT
Changes in psychiatric comorbidity measured by HSCL-25	HSCL-25. Consists of 25 questions. Each answer to a question has a value of 1-4. A total score over 1,75 points to psychological issues or impaired mental health	Change from baseline HSCL-25 score 12 months after FMT
Changes in dietary intake measured by FFQ	FFQ Change in dietary intakes measured using Food Frequency Questionnaire at baseline and at 3, 6 and 12 months after FMT will be examined. Energy measured as kcal, nutrition (gram) and different food groups reported as gram/day	Change from baseline FFQ score at 3, 6 and 12 months after FMT
Changes in life style measured by IPAQ	IPAQ Categorical Score Three levels (categories) of physical activity are proposed: Category 1: Low This is the lowest level of physical activity. Those individuals who not meet criteria for categories 2 or 3 are considered low/inactive. Category 2: Moderate Any one of the following 3 criteria: 3 or more days of vigorous activity of at least 20 minutes per day OR; 5 or more days of moderate-intensity activity or walking of at least 30 minutes per day OR; 5 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 600 MET-min/week. Category 3: High Any one of the following 2 criteria: Vigorous-intensity activity on at least 3 days and accumulating at least 1500 MET-minutes/ week OR; 7 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 3000 MET-minutes/week	Change from baseline IPAQ score at 3, 6 and 12 months after FMT
Gut microbiota composition and function	Microbiota analysis and SCFA in faeces	Change from baseline microbiota composition at 3, 6 and 12 months after FMT
Short difficult childhood questionnaire	Questions of childhood trauma, four or six questions	At baseling
Childhood trauma Questionnaire (CTQ)	A validated questionnaire to collect self-reported data about adverse childhood experiences	Once during the follow up period in the study
Heart rate variability (HRV)	A dysbiotic gut microbiota that signals with the vagal nerve can cause an exaggerated stress response in obesity characterised by decrease in heart rate variability.	HRV will be measured at inclusion and 3.months post FMT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Engraftment of donor microbiota at 1, 3, 6 and 12 months.	Comparison between baseline profile, post FMT and donor profile will show if engraftment of donor microbiota parallels clinical response to active FMT.	Inclusion, 2, 3, 6 and 12 months after FMT
Eating behaviour	Binge eating questionnaire	Change from baseline binge eating questionnaore score 12 months after FMT
Questionnaire about the impact of covid-19 on life style changes and eating habits	Participants which had undergone intervention and were in the follow up period, had all their appointments at the obesity clinic at UNN Harstad canceled, due to the covid-19 outbreak in the period march-20 to juli-20. This might have impacted their weight loss motivation and life style changes. We therefore asked them five questions, which we hope will shed light on the challenges they might encountered during the period of restrictions implemented by the Norwegian government.	Once during the follow up period in the study

Collaborators and Investigators

• Sponsor: University Hospital of North Norway
• Collaborators: University of Oslo; Norwegian University of Science and Technology; University of Tromso; Nordlandssykehuset HF; Lovisenberg Diakonale Hospital; Norwegian University of Life Sciences; Helse Nord
• Investigators: Principal Investigator: Per C Valle, PhD, University Hospital of North of Norway; Study Chair: Maria S Fjellstad, cand.med, University Hospital of North of Norway; Study Chair: Hege M Hanssen, M.Sc, University Hospital of North Norway

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: August 31, 2017
• First Submitted That Met QC Criteria: September 4, 2017
• First Posted (Actual): September 6, 2017

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid
• Other Study ID Numbers: 2017/1655

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No