Clinical trial NCT03273855: Randomized Controlled Trial of Fecal Microbiota Transplantation in Severe Obesity
Official title: Randomized Controlled Trial of Fecal Microbiota Transplantation in Severe Obesity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity, Morbid
Lead sponsor: University Hospital of North Norway
Sponsor class: OTHER
Collaborators: name: Norwegian University of Science and Technology
name: Lovisenberg Diakonale Hospital
name: Nordlandssykehuset HF
name: Helse Nord
name: University of Tromso
name: Norwegian University of Life Sciences
name: University of Oslo
First posted: 2017-09-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in individual weight loss (kg).
timeFrame: Change from baseline body weight at 12 months post FMT
Secondary outcomes:
measure: Change in individual weight loss (kg)
timeFrame: Change from baseline body weight at 3, 6 and 12 months after FMT
measure: Change in waist circumference (cm)
timeFrame: Change from baseline waist circumferense at 3, 6 and 12 months after FMT
measure: Changes in HbA1c (mmol/mol)
timeFrame: Change from baseline HbA1c at 3, 6 and 12 months after FMT
measure: Changes in fasting glucose (mmol/L)
timeFrame: Change from baseline fasting glucose at 3, 6 and 12 months after FMT
measure: Changes in insuline (pmol/L)
timeFrame: Change from baseline insuline at 3, 6 and 12 months after FMT
measure: Changes in C-peptide (pmol/L)
timeFrame: Change from baseline C-peptide at 3, 6 and 12 months after FMT
measure: Change in blood pressure
timeFrame: Change from baseline blood pressure at 3, 6 and 12 months after FMT
measure: Change in sedimentation rate (mm/t)
timeFrame: Change from baseline sedimentation rate at 3, 6 and 12 months after FMT
measure: Change in hs-CRP (mg/L)
timeFrame: Change from baseline hs-CRP at 3, 6 and 12 months after FMT
measure: Changes in multiplex cytokine panel (pg/mL)
timeFrame: Change from baseline cytokine panel at 3, 6 and 12 months after FMT
measure: Changes in biochemical parameters of hepatic steatosis (U/L)
timeFrame: Change from baseline biochemical parameters at 3, 6 and 12 months after FMT
measure: Changes in lipid profile based on HDL/LDL (mmol/L) and cholesterol (mmol/L)
timeFrame: Change from baseline lipid profile at 3, 6 and 12 months afterFMT
measure: Changes in life quality measured using RAND-36 questionnaire
timeFrame: Change from baseline RAND-36 score 12 months after FMT
measure: Changes in psychiatric comorbidity measured by HSCL-25
timeFrame: Change from baseline HSCL-25 score 12 months after FMT
measure: Changes in dietary intake measured by FFQ
timeFrame: Change from baseline FFQ score at 3, 6 and 12 months after FMT
measure: Changes in life style measured by IPAQ
timeFrame: Change from baseline IPAQ score at 3, 6 and 12 months after FMT
measure: Gut microbiota composition and function
timeFrame: Change from baseline microbiota composition at 3, 6 and 12 months after FMT
measure: Short difficult childhood questionnaire
timeFrame: At baseling
measure: Childhood trauma Questionnaire (CTQ)
timeFrame: Once during the follow up period in the study
measure: Heart rate variability (HRV)
timeFrame: HRV will be measured at inclusion and 3.months post FMT
Other outcomes:
measure: Engraftment of donor microbiota at 1, 3, 6 and 12 months.
timeFrame: Inclusion, 2, 3, 6 and 12 months after FMT
measure: Eating behaviour
timeFrame: Change from baseline binge eating questionnaore score 12 months after FMT
measure: Questionnaire about the impact of covid-19 on life style changes and eating habits
timeFrame: Once during the follow up period in the study
Locations:
city: Harstad
country: Norway
facility: University Hospital of North Norway
state: Troms
Study officials:
affiliation: University Hospital of North of Norway
name: Per C Valle, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of North of Norway
name: Maria S Fjellstad, cand.med
role: STUDY_CHAIR
affiliation: University Hospital of North Norway
name: Hege M Hanssen, M.Sc
role: STUDY_CHAIR
References: