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

Diabetes Clinical Trial

— DACH  

Official title:

Metabolic Outcome of Obese Subjects Receiving Fecal Microbiota Transplantation of Lean Versus Gastric Bypass Treated Subjects. A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06268990
• Other study ID #: FE 1159/6-1
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: University Hospital Bergmannsheil Bochum
• Contact: Wiebke K. Fenske, Prof. Dr.
• Phone: +492343026400
• Email: Wiebke.Fenske[@]bergmannsheil.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Insulin Resistance
• Metabolic Syndrome
• Morbid Obesity
• Obesity
• Obesity, Morbid
• PreDiabetes

Intervention

Procedure:
• Fecal microbiota transplantation
FMT is the transfer of fecal material containing gut microorganisms from a donor into the intestinal tract of a recipient

Locations

Country	Name	City	State
Austria	Department of Internal Medicine, Medical University Graz	Graz

Sponsors (2)

Lead Sponsor	Collaborator
Wiebke Kristin Fenske	Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity	Change in insulin sensitivity after FMT compared to baseline as assessed by hyperinsulinemic-euglycemic clamp technique	after 6 weeks treatment
Secondary	Insulin sensitivity	Change in insulin sensitivity after 16-/24-week treatment compared to baseline as assessed by hyperinsulinemic-euglycemic clamp.	after 16/24 weeks treatment
Secondary	Glucose homeostasis	Change in glucose homeostasis compared to baseline as assessed by HOMA-IR model, fasting glucose level, and HbA1C value	after 6-/16-/24-week treatment
Secondary	Body weight	Change in total body weight, body mass index (BMI) and body composition after 6-/16-/24-week treatment compared to baseline as assessed by Dual-energy X-ray absorptiometry, DXA)	after 6-/16-/24-week treatment
Secondary	Blood pressure	Change in blood pressure and antihypertensive medication compared to baseline.	after 6-/16-/24-week treatment
Secondary	Fasting lipid profile	Change in fasting lipid profile compared to baseline.	after 6-/16-/24-week treatment
Secondary	Fasting blood liver enzyme levels	Change in fasting blood liver enzyme levels and liver fat content (assessed by CAP values with the XL probe) compared to baseline	after 6-/16-/24-week treatment
Secondary	Dietary intake levels	Change in dietary intake assessed using MyFitnessPal compared to baseline.	after 6-/16-/24-week treatment
Secondary	Metabolic inflammation	Change in metabolic inflammation and endotoxemia as assessed by circulating pro-inflammatory cytokines (TNF-a, IL-6, IL-1ß) and bacterial endotoxins (lipopolysachharide (LPS), LPS-binding protein) compared to baseline	after 6-/16-/24-week treatment
Secondary	Gut hormones	Change in postprandial release of gut hormones (PYY, GLP-1, GIP, ghrelin, CCK), insulin and bacterial metabolites (SCFA, Bile acids) before (fasting condition) and during a standardized mixed meal test (MMT) (Fresubin 200ml, 400kcal) compared to baseline	after 6-/16-/24-week treatment
Secondary	Hunger and Satiety Scores	Change in Hunger and Satiety Scores assessed via visual analog scales during the MMT	daily
Secondary	Fecal microbiota composition	Change in diversity and composition of the fecal microbiota as assessed by 16S rRNA gene profiling compared to baseline	after 6-/16-/24-week treatment
Secondary	Health-related quality of life	Change in health-related quality of life and behavior as assessed by established self-report questionnaires compared to baseline measuring: (a) eating behavior including trait food craving (FCQ-T-r), hedonic eating (PFS), restrained eating, overeating, and binge eating (EDE-Q), and emotional eating as well as disinhibition (EI); (b) personality factors such as impulsivity (BIS-15) and reward sensitivity (BIS/BAS); (c) mental and physical health, including depression, anxiety, and substance use (PHQ-D), attention-deficit/hyperactivity disorder (ASRS), and quality of life (EQ-5D). All these questionnaires have established reliability and validity.	after 6-/16-/24-week treatment
Secondary	Tolerability of repeated FMT	Safety and tolerability of repeated FMT assessed by review of adverse event diary card	daily