Clinical trial NCT06268990: FMT in Obesity: RYGB vs. LEAN vs. Autologous FMT
Official title: Metabolic Outcome of Obese Subjects Receiving Fecal Microbiota Transplantation of Lean Versus Gastric Bypass Treated Subjects. A Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Morbid Obesity
Metabolic Syndrome
Diabetes
PreDiabetes
Insulin Resistance
Keywords: Fecal microbiota transfer
obesity
glucose homeostasis
bariatric surgery
gut microbiome
Lead sponsor: University Hospital Bergmannsheil Bochum
Sponsor class: OTHER
Collaborators: name: Medical University of Graz
First posted: 2024-02-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

- Inclusion criteria for patients

* 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

Inclusion criteria for RYGB-FMT intervention donors

* 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

Inclusion criteria for LEAN-FMT intervention donors

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

Exclusion Criteria:

Exclusion criteria for patients

• 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

Exclusion criteria for RYGB-FMT intervention donors

* 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.

Exclusion Criteria for Lean-FMT Intervention Donors • History of overweight or obesity in the past (BMI \> 25 kg/m2)

• 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.

Primary outcomes:
measure: Insulin sensitivity
timeFrame: after 6 weeks treatment
Secondary outcomes:
measure: Insulin sensitivity
timeFrame: after 16/24 weeks treatment
measure: Glucose homeostasis
timeFrame: after 6-/16-/24-week treatment
measure: Body weight
timeFrame: after 6-/16-/24-week treatment
measure: Blood pressure
timeFrame: after 6-/16-/24-week treatment
measure: Fasting lipid profile
timeFrame: after 6-/16-/24-week treatment
measure: Fasting blood liver enzyme levels
timeFrame: after 6-/16-/24-week treatment
measure: Dietary intake levels
timeFrame: after 6-/16-/24-week treatment
measure: Metabolic inflammation
timeFrame: after 6-/16-/24-week treatment
measure: Gut hormones
timeFrame: after 6-/16-/24-week treatment
measure: Hunger and Satiety Scores
timeFrame: daily
measure: Fecal microbiota composition
timeFrame: after 6-/16-/24-week treatment
measure: Health-related quality of life
timeFrame: after 6-/16-/24-week treatment
measure: Tolerability of repeated FMT
timeFrame: daily
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Internal Medicine, Medical University Graz
Study officials:
affiliation: University Hospital Bergmannsheil Bochum
name: Wiebke K. Fenske, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: