FMT in Obesity: RYGB vs. LEAN vs. Autologous FMT

NCT ID: NCT06268990

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-12-31

Brief Summary

This double-blinded proof-of-concept study is proposed to explore the effects of fecal microbiota transfer (FMT) in human subjects. Here we perform FMTs into obese recipients using stool from lean unoperated donors and from previously obese patients after successfull treatment with bariatric Roux-en-Y Gastric Bypass (RYGB) surgery. Obese patients treated with their own material (autologous FMT) serve as controls. After FMT treatment the functional impact of post-surgery microbiome changes on host energy consumption and regulation of blood glucose levels will be analysed. Additionally the variations on the microbiota and metabolite composition will be profiled using extensive sequencing analyses. The major aim of the study is to explore the scientific rationale for targeted gut microbiota modulation in management of obesity and related metabolic diseases.We estimate the transfer of microbiota from RYGB donors is superior to the transfer of lean microbiota at inducing reduced adiposity and improving high blood glucose levels in obese recipients. Each is better than a sham procedure (autologous FMT), which itself can also induce considerable short-term effects.

Detailed Description

Patients and stool donors (for RYGB-/Lean-FMT-intervention groups) will be recruited at the Endocrinology outpatient clinic at the University Hospital of Graz. Patients will be randomized in a 1:1:1 manner. In all three study groups, patients will be treated with FMT totaling three times every 7 days after an antibiotic pretreatment.

Patients randomized to the RYGB- FMT-intervention group will be treated with donor stool from previously obese patients successfully treated with RYGB surgery in terms of maintained weight reduction and improved glucose homeostasis. Patients randomized to Lean-FMT-intervention group will be treated with donor stool from un-operated, metabolically healthy and lean individuals, while patients randomized to the FMT-placebo group will be treated with autologous FMT.

For both allogenic FMT interventions, the donor stool from five different patients successfully treated with RYGB surgery (for RYGB-FMT intervention) and from five un-operated, lean and healthy individuals (for Lean-FMT intervention), respectively, will be anaerobically processed before active study period and stored at - 20° C for analysis and subsequent FMT.

In addition, stool from all 30 obese FMT recipients (FMT-intervention groups and FMT-placebo group) will be collected before the active study period, processed anaerobically and frozen at -80° C. Only stool samples from patients randomized to the FMT-placebo group (n=10) will be used as allogenic transplants.

Conditions

Morbid Obesity; Metabolic Syndrome; Diabetes; PreDiabetes; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

RYGB-FMT intervention group

morbidly obese patients randomized for FMT from patients successfully treated with RYGB surgery

Group Type: ACTIVE_COMPARATOR

Fecal microbiota transplantation

Intervention Type: PROCEDURE

FMT is the transfer of fecal material containing gut microorganisms from a donor into the intestinal tract of a recipient

LEAN-FMT intervention group

morbidly obese patients randomized for FMT from normal weight (lean) volonteers

Group Type: ACTIVE_COMPARATOR

Fecal microbiota transplantation

Intervention Type: PROCEDURE

FMT is the transfer of fecal material containing gut microorganisms from a donor into the intestinal tract of a recipient

M-FMT intervention group

morbidly obese patients randomized for autologous FMT

Group Type: SHAM_COMPARATOR

Fecal microbiota transplantation

Intervention Type: PROCEDURE

FMT is the transfer of fecal material containing gut microorganisms from a donor into the intestinal tract of a recipient

Interventions

Fecal microbiota transplantation

FMT is the transfer of fecal material containing gut microorganisms from a donor into the intestinal tract of a recipient

Intervention Type: PROCEDURE

Other Intervention Names

FMT

Eligibility Criteria

Inclusion Criteria

• Age >18 years
• Morbid obesity defined by a BMI ≥ 40 kg/m2
• Prediabetes or diabetes with HbA1C between ≥ 5.7 % OR
• Fasting plasma glucose > 5.6 mmol/l (> 100 mg/dl) (no caloric intake for at least 8 hours) OR
• Random plasma glucose > 11.1 mmol/l (> 200 mg/dl)
• Informed consent

• Sustained total weight loss of ≥30% ≥12 months after RYGB surgery
• HbA1c < 6.5% without insulin treatment or oral antidiabetic medication
• Age >18 years
• Informed consent

• Normal weight (BMI ≥ 20 to < 25 >18 years
• Informed consent

Exclusion Criteria

• Non-Compliance

• Insulin dependent diabetes mellitus, treated with GLP-1 agonists or poorly controlled on oral antidiabetic medications (HbA1C > 8%)
• Use of any weight loss medication or participation in a weight loss program
• History of recent body weight change (defined as body weight loss or body weight gain of ≥ 5 kg within the two months preceding study enrolment).
• Use of immunosuppressive medication or immune modulators (glucocorticoids, methotrexate, tacrolimus, cyclosporine, thalidomide, interleukin-10 or -11) within the last three months preceding study enrolment.
• Congenital or acquired immunodeficiencies.
• Anatomical reconstruction of the nutrient passage (i.e. hemicolectomy, resection of small bowel, gastrectomy, sleeve gastrectomy, gastric bypass surgery, biliopancreatic diversion, fundoplication etc) or cholecystectomy.
• Chronic diarrhoea
• History of serious chronic disease including malignancy, rheumatic heart disease, endocarditis, or valvular disease (due to risk of bacteremia)
• Any condition, based on clinical judgment that may make study participation unsafe
• Pregnancy or Breast Feeding

• Intake of pre-, pro- or antibiotics within < 3 months before study entry
• Use of immunosuppressive medication or immune modulators (glucocorticoids, methotrexate, tacrolimus, cyclosporine, thalidomide, interleukin-10 or -11) within the last three months preceding study enrolment.
• Congenital or acquired immunodeficiencies.
• Chronic or acute infectious diseases (specified under 6.2.1)
• Drug abuse
• Anatomical reconstruction of the nutrient passage other than surgical RYGB configuration (i.e. hemicolectomy, resection of small bowel, fundoplication, LSG-to-RYGB transformation etc) or cholecystectomy.
• History of recent body weight change (defined as body weight loss or body weight gain of ≥ 5 kg within the two months preceding study enrolment).
• Chronic diarrhoea or steatorrhea or acute gastrointestinal infection within ≤ 3 months before study entry.
• History of serious chronic disease including malignancy, chronic kidney disease (eGFR < 60 ml/min), heart failure (NYHA ≥ III).
• Any further condition, based on clinical judgment that may disqualify the candidate as an appropriate donor.

• History of recent body weight change (defined as body weight loss or body weight gain of ≥ 5 kg within the two months preceding study enrolment).

• HbA1C > 6.5% or treatment with insulin or oral anti-diabetic medication.

• Use of any weight loss medication or participation in a weight loss program

• Use of immunosuppressive medication or immune modulators (glucocorticoids, methotrexate, tacrolimus, cyclosporine, thalidomide, interleukin-10 or -11) within the last three months preceding study enrolment.

• Congenital or acquired immunodeficiencies.

• Chronic or acute infectious diseases (specified under 6.2.1)

• Drug abuse

• Anatomical reconstruction of the nutrient passage (i.e. hemicolectomy, resection of small bowel, fundoplication etc) or cholecystectomy.

• Chronic diarrhoea or acute gastrointestinal infection within ≤ 3 months before study entry.

• History of serious chronic disease including malignancy, chronic kidney disease (eGFR < 60 ml/min), heart failure (NYHA ≥ III).

• Any further condition, based on clinical judgment that may disqualify the candidate as an appropriate donor.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Graz

OTHER

Sponsor Role: collaborator

Wiebke Kristin Fenske

OTHER

Sponsor Role: lead

Responsible Party

Wiebke Kristin Fenske

Prof. Dr.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Wiebke K. Fenske, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Bergmannsheil Bochum

Locations

Department of Internal Medicine, Medical University Graz

Graz, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Wiebke K. Fenske, Prof. Dr.

Role: CONTACT

Wiebke.Fenske@bergmannsheil.de

+492343026400

Facility Contacts

Julia K Mader, Assoc. Prof.

Role: primary

julia.mader@medunigraz.at

+43 316 38582383

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

FE 1159/6-1

Identifier Type: -

Identifier Source: org_study_id