Synbiotics and Fecal Microbiota Transplantation to Treat Non-Alcoholic Steatohepatitis

NCT05821010 | Recruiting Phase 2 DMC

• 1 other identifier: NL81001.018.22
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate the therapeutic potential of A. soehngenii and pasteurized A. muciniphila combined with B. animalis subsp. lactis and fructo-oligosaccharides with and without conditioned vegan lyophilized fecal microbiota transplantation capsules to reduce NASH in patients with fibrotic NASH. The main questions to answer are:

1. 1.Can NASH be treated by altering the gut microbiota using LFMT capsules?
2. 2.Can NASH be treated using a syntrophic cocktail of synbiotics and will these strains strengthen the effect of FMT?
3. 3.What are the underlying mechanism by which the aforementioned treatments attenuate NASH?

Conditions

Non Alcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease; Fecal Microbiota Transplantation; FMT; Prebiotics; Probiotics; Microbiome; Intestinal Microbiome; Gut Microbiome

Outcome Measures

Primary Outcomes (1)

• Liver histology

  Alteration of liver histology in subjects with NASH and fibrosis stage 0-3, with an alteration defined as change of steatohepatitis by ≥1 SAF-A point, or a change in ≥ 1 stage liver fibrosis.

  baseline and after 24 weeks

Secondary Outcomes (19)

• MRI

  baseline and after 24 weeks

• Fibroscan

  baseline and after 24 weeks

• Liver enzymes (blood)

  baseline and after 24 weeks; 8 and 16 weeks for safety.

• Immunological data

  baseline and after 24 weeks

• Plasma lipids

  baseline and after 24 weeks

Study Arms (2)

LFMT-capsules

EXPERIMENTAL

LFMT-capsules. 3 times bulk, and further continuous administration. This arm is also treated pre- and probiotics.

Combination Product: Lyophilized fecal microbiota transplantation capsules; Dietary Supplement: A. soehngenii; Dietary Supplement: Pasteurized A. muciniphila; Dietary Supplement: B. animalis subsp. lactis; Dietary Supplement: Fructo-oligosaccharides

Placebo

PLACEBO COMPARATOR

Placebo-capsules. 3 times bulk, and further continuous administration. This arm is also treated pre- and probiotics.

Combination Product: Placebo capsules; Dietary Supplement: A. soehngenii; Dietary Supplement: Pasteurized A. muciniphila; Dietary Supplement: B. animalis subsp. lactis; Dietary Supplement: Fructo-oligosaccharides

Interventions

Lyophilized fecal microbiota transplantation capsules COMBINATION_PRODUCT

Oral administration (capsule)

LFMT-capsules

Placebo capsules COMBINATION_PRODUCT

Oral administration (capsule)

Placebo

A. soehngenii DIETARY_SUPPLEMENT

Oral administration (capsule)

LFMT-capsules; Placebo

Pasteurized A. muciniphila DIETARY_SUPPLEMENT

Oral administration (capsule)

LFMT-capsules; Placebo

B. animalis subsp. lactis DIETARY_SUPPLEMENT

Oral administration (capsule)

LFMT-capsules; Placebo

Fructo-oligosaccharides DIETARY_SUPPLEMENT

Oral administration (dissolved in water)

LFMT-capsules; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• biopsy-proven NASH obtained up to 32 weeks before screening: SAF Steatosis score ≥1, Activity ≥2, Fibrosis \<4; 50% of participants should at least have NASH fibrosis stage 1, 2 or 3 according to the NASH CRN fibrosis staging system based on tandem reading of two expert liver pathologists
• fluency in Dutch or English
• participants should be able to understand the information and give informed consent

You may not qualify if:

• Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year before screening (significant alcohol consumption is defined as more than 2 international units/day for females and more than 3 international units/day for males, on average; 1 international unit contains ±14 grams of alcohol)
• liver cirrhosis or hepatocellular carcinoma
• hepatitis B and/or C
• auto-immune hepatitis
• Wilson's disease
• primary sclerosing cholangitis
• primary biliary cholangitis
• alpha-1-antitripsine deficiency and hemochromatosis
• history of liver transplant, current placement on a liver transplant list
• use of pre-, pro- or synbiotics
• use of systemic antibiotics 3 month prior to randomization
• use of tamoxifen, methotrexate or amiodarone
• prior or planned bariatric surgery
• active GLP-1 receptor agonist treated diabetes mellitus
• bleeding disorder

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC

Amsterdam, North Holland, 1105AZ, Netherlands

RECRUITING

Related Publications (1)

• Augustijn QJJ, Grefhorst A, de Groen P, Wortelboer K, Seegers JFM, Gul IS, Suenaert P, Verheij J, de Vos WM, Herrema H, Nieuwdorp M, Holleboom AG. Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis. BMJ Open. 2025 Jan 9;15(1):e088290. doi: 10.1136/bmjopen-2024-088290.

  PMID: 39788762 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

fructooligosaccharide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• A.G. Holleboom, MD, PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Quinten Augustijn, MD

CONTACT

+31205661267; q.j.augustijn@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Doubleblind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized placebo-controlled trial

Study Record Dates

• First Submitted: March 8, 2023
• First Posted: April 20, 2023
• Study Start: March 17, 2023
• Primary Completion: February 20, 2026
• Study Completion (Estimated): August 20, 2026
• Last Updated: August 27, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)