Stool transplantation for treatment of insulin resistance in morbidly obese patients
| ISRCTN | ISRCTN68710020 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68710020 |
| ClinicalTrials.gov number | NCT02970877 |
| Secondary identifying numbers | 16-5475 |
- Submission date
- 17/06/2016
- Registration date
- 11/07/2016
- Last edited
- 16/06/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
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 July 2021
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. Dr Katherine Schwenger (public)
Katherine.schwenger@uhnresearch.ca
Contact information
Scientific
University Health Network, Toronto General Hospital
200 Elizabeth St, 9-NU-973
Toronto, ON
M5G 2C4
Canada
 ORCID ID |
0000-0002-8956-7059 |
|---|---|
| Phone | +1 (0)416 340 5159 |
| johane.allard@uhn.on.ca |
Public
Department of Medicine, Division of Gastroenterology
Toronto General Hospital, University Health Network
200 Elizabeth St
Eaton North, 10th floor Room 243
Toronto, ON
M5G 2C4
Canada
| Phone | +1 (0)416 340 4413 |
|---|---|
| Katherine.schwenger@uhnresearch.ca |
Study information
| Study design | Single-center Phase II double-blind parallel-group randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| 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. |
| Study 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(s) | University Health Network Research Ethics Board, 11/01/2017, ref: 16-5475-A |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Fecal microbiota transplant |
| Primary outcome measure | 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 study start date | 01/07/2016 |
| Overall study end date | 01/07/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 48 |
| Total final enrolment | 28 |
| 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 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 | 01/03/2017 |
| Recruitment end date | 31/10/2020 |
Locations
Countries of recruitment
- Canada
Study participating centre
Toronto, ON
M5G 2C4
Canada
Sponsor information
Hospital/treatment centre
200 Elizabeth Street
Toronto, ON
M5G 2C4
Canada
| Website | http://www.uhn.ca/ |
|---|---|
"ROR" |
https://ror.org/042xt5161 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
- Location
- Canada
Results and Publications
| Intention to publish date | 01/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | We will present data first in the form of abstracts, posters, and oral presentations, as soon as they become available. Full manuscripts will be submitted for publication in scientific journals. 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/). |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 14/10/2022 | 16/06/2023 | Yes | No |
Editorial Notes
16/06/2023: Publication reference added.
31/01/2022: The following changes have been made to the trial record:
1. The study contact has been updated and the plain English summary has been updated accordingly.
2. The intention to publish date was changed from 01/12/2021 to 01/12/2022.
09/12/2020: The following changes have been made to the trial record:
1. The recruitment end date was changed from 31/12/2020 to 31/10/2020.
2. The intention to publish date was changed from 01/07/2021 to 01/12/2021.
3. Total final enrolment number added.
10/01/2020: The following changes have been made:
1. The recruitment end date has been changed from 01/12/2019 to 31/12/2020.
2. The overall trial end date has been changed from 01/05/2020 to 01/07/2021.
23/05/2019: Internal review.
08/03/2019: Contact details updated, IPD sharing statement added.
05/03/2019: Internal review.
03/08/2018: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/08/2016 to 01/03/2017.
2. The recruitment end date was changed from 01/08/2017 to 01/12/2019.
3. The overall trial end date was changed from 31/12/2017 to 01/05/2020.
4. The intention to publish date was changed from 31/12/2017 to 01/12/2020.
02/08/2018: ClinicalTrials.gov number and ORCIDs added.
30/08/2017: Ethics approval has been added.
