Condition category
Nutritional, Metabolic, Endocrine
Date applied
17/06/2016
Date assigned
11/07/2016
Last edited
23/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
More and more people in Canada and around the world are severely (morbidly) obese (very overweight), and those people are at high risk of not being able to control their blood sugar levels very well (insulin resistance (IR)) and also of developing diabetes. Most morbidly obese people cannot lose weight. Weight loss surgery (bariatric surgery) can help, but it has some risks and is not available to all patients. Therefore, alternative treatments are needed. Gut flora refers to the microorganisms that live in the digestive tract with the relationship between the multitude of bacteria in the gut and their human host beneficial to both parties. An altered composition of the gut bacteria (that is, a change in the type and number of bacteria present) might contribute to obesity and IR. Several animal studies show that giving stool from lean mice or humans to obese mice (stool transplant) can make the obese animals lose weight and improve IR. One human study has confirmed this. This study is looking at whether stool transplant from healthy lean people will improve blood sugar control, weight, and other obesity related problems in morbidly obese patients with IR.

Who can participate?
Morbidly obese patients, age 18 years and older, referred to the Toronto Western Hospital Bariatric Surgery Clinic, Toronto, Canada, for weight loss surgery but decided not to go ahead with it. hHealthy lean volunteers are also recruited as stool donors.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 receive a stool transplant from a healthy lean donor (treatment group). Those in group 2 receive a stool transplant prepared from the participants own stool (placebo, or control, group) After the stool transplant, participants come back to the hospital after 1 and after 3 months when they are tested for insulin resistance and other blood work, weight, appetite and food intake, quality of life, depression, and anxiety, gut bacteria and bacterial products in stool and blood, and the bacteria found in the mouth. In addition, before the stool transplant, the bacteria attached to the gut wall will be compared to those found in stool. Participants are asked to give blood, stool, and scrape samples from teeth and tongue, and to fill out questionnaires at each visit. The stool transplant is done through a tube that the doctor inserts into the rectum (colonoscopy). During the procedure, a small piece of the gut wall is collected as well. Stool donors are carefully screened to make sure they do not have any disease they might pass on to the patients who will receive their stool. Each donor gives blood, stool, and urine samples for screening and 3 to 5 stool samples for the study.

What are the possible benefits and risks of participating?
It is not yet known whether the stool transplant works, but if it does, it is possible that blood sugar control will improve. Participants may also lose weight and depression and anxiety may improve.
Stool transplants have been described in the literature in over 1000 patients, mostly for treatment of severe diarrhoea due to a gut infection. From these reports, it is known that about 1/3 of the patients will have minor gastrointestinal problems like bloating, abdominal pain, diarrhoea, constipation, nausea; or fever, but they usually go away within 2 days. More serious problems are rare (less than 1% of patients), including heart and lung problems, strong bleeding, infections, or a hole (perforation) of the bowel.

Where is the study run from?
University Health Network in Toronto, Ontario, (Canada)

When is study starting and how long is it expected to run for?
July 2016 to December 2017

Who is funding the study?
Canadian Institutes for Health Research.

Who is the main contact?
1.Professor Johane Allard (scientific)
johane.allard@uhn.on.ca
2. Monica Ponta (public)
monica.ponta@uhnresearch.ca

Trial website

Contact information

Type

Scientific

Primary contact

Prof Johane Allard

ORCID ID

Contact details

University Health Network
Toronto General Hospital
200 Elizabeth St
9-NU-973
Toronto
ON
M5G 2C4
Canada
+1 416-340-5159
johane.allard@uhn.on.ca

Type

Public

Additional contact

Dr Monica Ponta

ORCID ID

Contact details

University Health Network
Toronto General Hospital
200 Elizabeth St
10-EN-243a
Toronto
ON
M5G 2C4
Canada
+1 416-340-4104
monica.ponta@uhnresearch.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

16-5475

Study information

Scientific title

Fecal microbiota transplant from healthy lean donors to morbidly obese individuals: effect on insulin resistance and other obesity-related parameters. A randomized controlled trial.

Acronym

Fecal transplant bariatric

Study hypothesis

Main hypothesis:
Fecal microbiota transplant (FMT) from healthy lean donors to morbidly obese individuals with insulin resistance (IR) (homeostasis model of assessment for IR, HOMA-IR more than 2.73) will improve HOMA-IR

Secondary hypotheses:
1. FMT will also reduce weight, appetite, and food intake
2. FMT will improve quality of life, depression and anxiety scores
3. FMT will change IM as well as fecal and serum metabolome
4. Improvement in clinical parameters (IR, weight, appetite, mood scores) are associated with specific changes in IM or metabolites (eg. short-chain fatty acids)
5. Exploratory: Explore changes in OM and potential associations between OM and IM and their potential relationships with obesity/metabolic parameters
6. Baseline: Comparing luminal (fecal) with mucosa-adherent microbiome and examine their potential relationships with obesity/metabolic parameters

Ethics approval

Not provided at time of registration

Study design

Single-center, Phase II, double-blind, parallel-group randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Morbid obesity and insulin resistance

Intervention

Morbidly obese participants will receive one single dose of fecal filtrate prepared from feces of healthy lean pre-screened donors (allogenic FMT = treatment arm) or prepared from their own feces (autologous FMT = control arm, placebo arm) per colonoscopy.

Patients will be followed for 3 months post FMT.

Patients will be allocated to allogenic or autologous FMT by randomization with a 1:1 chance to be allocated to either group. As diet can influence the IM composition (131, 132), all patients will receive a brief initial counselling on a healthy diet, where they will be provided with basic advice for a healthy diet and appropriate physical activity.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

Insulin resistance, measured using the homeostasis model of assessment for insulin resistance (HOMA-IR) at baseline and 1 and 3 months after FMT

Secondary outcome measures

1/ Weight (in kg) and body mass index (weight kg / height m²) measured with a scale at baseline and 1 and 3 months after FMT
2. Change in body weight (% change) between baseline and 1 and 3 months after FMT
3. Appetite score, assessed with a visual analogue rating scale at baseline, 1, and 3 months after FMT
4. Quality of life, measured using the RAND 36-Item Health Survey 1.0 at baseline and 1 and 3 months after FMT
5. Anxiety and depression scores, measured using the Hamilton Anxiety Rating Scale and the Montgomery-Åsberg Depression Rating Scale, respectively, at baseline and 3 months after FMT

Overall trial start date

01/07/2016

Overall trial end date

31/12/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Morbidly obese men and women, age 18 years or older, fulfilling the 1991 NIH criteria (BMI >40 kg/m2 or BMI >35–40 kg/m2 with other severe weight loss responsive comorbidities)
2. Referred to the Bariatric Clinic at the Toronto Western Hospital for weight loss surgery, but declining or deferring the surgery
3. Insulin resistant, which is defined as having a HOMA-IR value >2.73

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

48

Participant exclusion criteria

1. Regular intake of: non-steroidal anti-inflammatory drugs; iron supplements; prebiotics or probiotics from other than food sources, antibiotics, or any experimental drug in the 3 months prior to study entry
2. Type 1 or type 2 diabetes
3. Chronic gastrointestinal diseases
4. Previous gastrointestinal surgery modifying the anatomy
5. Smoking;
6. Pregnancy
7. Breastfeeding

Recruitment start date

01/08/2016

Recruitment end date

01/08/2017

Locations

Countries of recruitment

Canada

Trial participating centre

University Health Network
200 Elizabeth Street
Toronto, ON
M5G 2C4
Canada

Sponsor information

Organisation

University Health Network

Sponsor details

200 Elizabeth Street
Toronto
ON
M5G 2C4
Canada

Sponsor type

Hospital/treatment centre

Website

http://www.uhn.ca/

Funders

Funder type

Government

Funder name

Canadian Institutes of Health Research

Alternative name(s)

Instituts de Recherche en Santé du Canada, CIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Canada

Results and Publications

Publication and dissemination plan

We will present data first in the form of abstracts, posters, and oral presentations, as soon as they become available (expected fall 2017). Full manuscripts will be submitted for publication in scientific journals (expected December 2017). In addition, the progress of the study and the results will be presented to the Bariatric Surgery Clinic Staff and Students in private sessions. We are also planning to disseminate the results through the website of the Canadian Obesity Network (www.obesitynetwork.ca/).

Intention to publish date

31/12/2017

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes