The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD)

NCT04465032 | Unknown Phase 4 DMC

• 1 other identifier: GE17-05
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The primary objective is to study the effect of consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are weight, waist, blood pressure, metabolic parameters (including glucose, cholesterol, pancreatic beta-cell function, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition and liver enzymes. Stool samples will be collected for microbiota analysis at time point 0, 3, 6 and 12 weeks.

Conditions

NAFLD

Outcome Measures

Primary Outcomes (1)

• the effect on consecutive FMT on liver fat accumulation

  measured by MRI Livermultiscan

  12 weeks

Secondary Outcomes (16)

• alterations in anthropometric data

  3, 6 and 12 weeks

• alterations in anthropometric data

  3, 6 and 12 weeks

• alterations in anthropometric data

  3, 6 and 12 weeks

• alterations in pancreatic beta-cell function and insulin resistance

  3, 6 and 12 weeks

• alterations in pancreatic beta-cell function and insulin resistance

  3, 6 and 12 weeks

Study Arms (2)

Autologous gut microbiome transplantation

ACTIVE COMPARATOR

Three autologous (own) fecal transplantations (at baseline, 3 and 6 weeks)

Other: Gut microbiome transplantation

Allogenic gut microbiome transplantation

EXPERIMENTAL

Three allogenic (lean donor) fecal transplantations (at baseline, 3 and 6 weeks)

Other: Gut microbiome transplantation

Interventions

Gut microbiome transplantation OTHER

Fecal transplantation will be performed at baseline and at week 3 and 6. At the Department of Clinical Bacteriology either the autologous or allogenic feces is prepared for donation by an experienced lab co-worker. The fecal transplantation will be performed via gastroduodenal endoscopy at the Department of Gastroenterology by an experienced endoscopist. To alleviate the procedure, midazolam is offered to the participants. Following placement of the endoscope in the horizontal duodenum, 150 mL feces solution is inserted via the endoscope.

Also known as: Fecal transplantation

Allogenic gut microbiome transplantation; Autologous gut microbiome transplantation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Obese (BMI \> 27 kg/m2)
• Males and postmenopausal females
• Aged 18 to 70 years
• Hepatic steatosis defined as increased hyperechogenicity of the liver on abdominal ultrasound and/or histological signs of steatosis
• Written informed consent

You may not qualify if:

• Any other liver disease than NAFLD/NASH
• Present excessive alcohol use defined as \> 2 units/day
• Recent use (\< 3 months) of antibiotics
• use of possible drugs interfering microbiota or recent (\< 3 months) changes in dosages
• use of GLP-1 RA or SU-derivatives
• Recent (\< 3 months) weight change (\>5%)
• Cardiovascular co-morbidity defined as heart failure, coronary insufficiency and hypertension in past history
• Previous use of glucocorticosteroids, hormonal substitution, pagitaxel, theofyllin, amiodarone, myelosuppresive agents.
• A psychiatric, addictive or any other disorder that compromises the subjects ability to understand the study content and to give written informed consent for participation in the study

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Dutch Donor Feces Bank: collaborator
• Vedanta Biosciences: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

Related Publications (1)

• Groenewegen B, Ruissen MM, Crossette E, Menon R, Prince AL, Norman JM, Ballieux BEPB, Lamb HJ, Terveer EM, Keller JJ, Tushuizen ME. Consecutive fecal microbiota transplantation for metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial. Gut Microbes. 2025 Dec;17(1):2541035. doi: 10.1080/19490976.2025.2541035. Epub 2025 Aug 4.

  PMID: 40755230 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Central Study Contacts

Maarten Tushuizen, MD PhD

CONTACT

+31 71 5263541; m.e.tushuizen@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded RCT, randomization by Dutch Donor Feces Bank
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle investigator

Model Details: Double-blinded randomized controlled trial, randomization 1:1 to allogenic and autologous gut microbiome transplantation

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: July 9, 2020
• Study Start: December 10, 2019
• Primary Completion: March 31, 2021
• Study Completion: December 31, 2021
• Last Updated: July 9, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)