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

NCT06268990 | Recruiting

• 1 other identifier: FE 1159/6-1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Fecal microbiota transfer; obesity; glucose homeostasis; bariatric surgery; gut microbiome

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity

  Change in insulin sensitivity after FMT compared to baseline as assessed by hyperinsulinemic-euglycemic clamp technique

  after 6 weeks treatment

Secondary Outcomes (13)

• Insulin sensitivity

  after 16/24 weeks treatment

• Glucose homeostasis

  after 6-/16-/24-week treatment

• Body weight

  after 6-/16-/24-week treatment

• Blood pressure

  after 6-/16-/24-week treatment

• Fasting lipid profile

  after 6-/16-/24-week treatment

Study Arms (3)

RYGB-FMT intervention group

ACTIVE COMPARATOR

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

Procedure: Fecal microbiota transplantation

LEAN-FMT intervention group

ACTIVE COMPARATOR

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

Procedure: Fecal microbiota transplantation

M-FMT intervention group

SHAM COMPARATOR

morbidly obese patients randomized for autologous FMT

Procedure: Fecal microbiota transplantation

Interventions

Fecal microbiota transplantation PROCEDURE

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

Also known as: FMT

LEAN-FMT intervention group; M-FMT intervention group; RYGB-FMT intervention group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Wiebke Kristin Fenske: lead
• Medical University of Graz: collaborator

Study Sites (1)

Department of Internal Medicine, Medical University Graz

Graz, 8010, Austria

RECRUITING

MeSH Terms

Conditions

Obesity, Morbid; Metabolic Syndrome; Diabetes Mellitus; Prediabetic State; Insulin Resistance; Obesity

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Wiebke K. Fenske, Prof. Dr.

  University Hospital Bergmannsheil Bochum

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wiebke K. Fenske, Prof. Dr.

CONTACT

+492343026400; Wiebke.Fenske@bergmannsheil.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: January 29, 2024
• First Posted: February 21, 2024
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Locations

AU (1)