Clinical trial NCT05002153: The Role of Microbiome in Recurrent Obesity
Official title: The Role of Microbiome in Recurrent Obesity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Weight Loss
FMT
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Weizmann Institute of Science
First posted: 2021-08-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This past century witnessed a significant increase in the prevalence of obesity, when since 1980 worldwide obesity has more than doubled. According to the World Health Organization, 39% of adults from the age of 18 years or older are overweight while 13% are obese. Successful maintenance of weight loss as losing at least 10% of the initial body weight and maintaining it for at least one year. However, keeping the low body weight is rarely maintained, as 80% of people who lost 10% of their body weight will return to their initial weight within a year. When weight loss is maintained for 2-5 years the chance of long term success was shown to dramatically increase.

Although there is no agreement as to what contributes to the recurrent weight regain phenomenon (also known as 'weight cycling' or 'yo-yo diet'), it is strongly associated with the risk of developing metabolic risk factors and their complications including heart disease and all-cause mortality.

Altering the gut microbiota is one method to treat disease states associated with gut bacteria. For instance, fecal microbiota transplant (FMT) or fecal bacteriotherapy, is the process of transferring stool from a healthy donor to another. The goal of FMT is to restore host health by increasing diversity and function of the gut microbiota. The main advantage of FMT over probiotics is its ability to transplant the entire gut microbiota and metabolites from the donor to the recipient.

Although numerous individual microbes have been identified as related to obesity, multiple studies suggest that loss of microbial diversity has a stronger impact on the development of metabolic dysfunction, this diversity may be restored by FMT.

This study will determine whether microbiome modulation might be a possible future target against recurrent obesity in humans, and whether orally administered FMT from a lean donor, post weight loss might be an effective intervention to prevent weight regain.

Detailed description: This is a placebo-controlled, double blinded interventional study evaluating high intensity oral fecal microbiota transplantation from lean healthy donors to prevent weight regain after a successful weight loss intervention. Volunteers will be recruited in the following ways: e-mail, and social media. Volunteers wishing to participate will be asked to complete a questionnaire regarding the aforementioned inclusion and exclusion criteria. Volunteers who qualify for the study will be invited to an introductory meeting at the Weizmann Institute of Science. The details of the experiment and potential risks or discomforts involved in it will be presented, after which the volunteers will sign informed consent forms. Volunteers will start the study and become active participants for a maximal duration of two years, depending on the weight loss process.

The study will comprise of four parts:

1. Baseline - one week of profiling and screening.
2. Nutritional intervention - weight loss intervention which will be based on Mediterranean hypocaloric diet restriction. Meetings will occur twice a month starting from the second week of the study for a three-month period.
3. FMT/ Placebo intervention - 5 weekly cycles of high intensity lean donor FMT/placebo will be administered starting after reaching a weight loss of 5 to 10% of total body weight. Each cycle will consist of 10 capsules administered on two consecutive days (total 100 capsules)
4. Follow-up meetings - total follow up of one year after FMT cycles. Meetings will occur every month for the first 3 months of the study, and every 3 months, Afterwards.

Eligibility criteria: Inclusion Criteria:

* 28\<BMI\>35
* Age: 18-65
* Capable of working with a smartphone application

Exclusion Criteria:

* Consumption of antibiotics/probiotics/oral antifungals 3 months prior to the first day of the experiment.
* Pregnancy, fertility treatments, breastfeeding women six months prior to enrollment and during the study.
* Chronic disease (e.g. AIDS, Cushing syndrome, CKD, acromegaly, hyperthyroidism/hypothyroidism etc.)
* Cancer and recent anticancer treatment
* Psychiatric disorders
* Coagulation disorders
* IBD (inflammatory bowel diseases)
* Bariatric surgery
* Eating disorders (Anorexia nervosa. Bulimia nervosa. Binge eating disorder, Night eating syndrome).
* Alcohol or substance abuse
* Weight loss attempts one year prior to the first day of the experiment - independent or with a dietitian.

Primary outcomes:
measure: Microbiome Profiling
timeFrame: 1.5 years
measure: Reaching Target Weight
timeFrame: 1.5 years
Secondary outcomes:
measure: Glycemic Response
timeFrame: 1.5 years
measure: Metabolic Rate
timeFrame: 1.5 years
measure: Substrate Utilization
timeFrame: 1.5 years
Other outcomes:
Locations:
Study officials:
affiliation: Asaf Harofe Medical Center, Be'er Yaacov, Israel
name: Ilan Youngster, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005 Jul;82(1 Suppl):222S-225S. doi: 10.1093/ajcn/82.1.222S.
citation: Mackie GM, Samocha-Bonet D, Tam CS. Does weight cycling promote obesity and metabolic risk factors? Obes Res Clin Pract. 2017 Mar-Apr;11(2):131-139. doi: 10.1016/j.orcp.2016.10.284. Epub 2016 Oct 20.
citation: Wing RR, Hill JO. Successful weight loss maintenance. Annu Rev Nutr. 2001;21:323-41. doi: 10.1146/annurev.nutr.21.1.323.
citation: Bangalore S, Fayyad R, Laskey R, DeMicco DA, Messerli FH, Waters DD. Body-Weight Fluctuations and Outcomes in Coronary Disease. N Engl J Med. 2017 Apr 6;376(14):1332-1340. doi: 10.1056/NEJMoa1606148.
citation: Lee P, Yacyshyn BR, Yacyshyn MB. Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT). Diabetes Obes Metab. 2019 Mar;21(3):479-490. doi: 10.1111/dom.13561. Epub 2018 Nov 20.
citation: Thaiss CA, Itav S, Rothschild D, Meijer MT, Levy M, Moresi C, Dohnalova L, Braverman S, Rozin S, Malitsky S, Dori-Bachash M, Kuperman Y, Biton I, Gertler A, Harmelin A, Shapiro H, Halpern Z, Aharoni A, Segal E, Elinav E. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature. 2016 Dec 22;540(7634):544-551. doi: 10.1038/nature20796. Epub 2016 Nov 24.