Impact of FMT on the Phenome in Patients With NAFLD and Fibrosis

NCT06024681 | Completed

• 3 other identifiers: ICL_21SM678729652221/LO/0454
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot experimental medicine interventional study is to explore the degree of transferability of the gut microbiome and associated metabolomic changes in patients with non-alcoholic fatty liver disease (NAFLD) and fibrosis who receive faecal microbiota transplant (FMT). The main questions is aims to answer is:

• To what extent is the gut microbiome transferable from donor to recipient in patients with NAFLD with fibrosis who receive FMT?
• What are the dynamics of how the gut microbiome changes over time in these patients?
• To what degree does the recipient metabolome change in association with this? Participants will receive up to three capsulised FMT preparations prepared from a donor selected rationally based upon their metabolomic characteristics. They will be asked to attend for serial clinical assessments (including FibroScan and MRE/ MRI-PDFF), and will also be asked to provide serial blood, urine and stool samples for assessment of microbiome and metabolome profiling.

Conditions

Non-Alcoholic Fatty Liver Disease; Fecal Microbiota Transplantation

Keywords

NAFLD; Gut microbiome; Metabolomics

Outcome Measures

Primary Outcomes (2)

• Change in faecal microbiome composition

  Using 16S rRNA gene sequencing and shotgun metagenomic sequencing

  24 weeks after initial FMT

• Change in gut microbial metabolite composition

  Using 1H-NMR and mass spectrometry

  24 weeks after initial FMT

Secondary Outcomes (8)

• Changes in liver fat on MRI

  16 weeks after initial FMT

• Changes in liver fat on FibroScan

  16 weeks after initial FMT

• Changes in liver stiffness on MRI

  16 weeks after initial FMT

• Changes in liver stiffness on FibroScan

  16 weeks after initial FMT

• Changes in HbA1c

  24 weeks after initial FMT

Study Arms (1)

NAFLD patients

EXPERIMENTAL

Patients receiving capsulised FMT

Other: Faecal microbiota transplant

Interventions

Faecal microbiota transplant OTHER

Capsulised faecal microbiota transplant prepared from rationally selected donor, based upon donor metabolomic charateristics

NAFLD patients

Eligibility Criteria

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

You may qualify if:

• years of age.
• Previously-diagnosed NAFLD, with predicted fibrosis based upon non-invasive assessment with FibroScan (i.e. liver stiffness measurement (LSM) \> 8kPa).
• Raised liver ALT (\> 30IU/l for men, \> 19IU/l for women) or AST (\> 37IU/l for men, \> 31IU/l for women) with negative non-invasive liver screen (including negative screen for viral hepatitis, autoimmune liver disease and metabolic liver disease, and normal echocardiogram within two years in the scenario where congestive hepatopathy may be considered).
• Able to consent for themselves in English.

You may not qualify if:

• Severe or life-threatening food allergy.
• Pregnant or lactating women; or women trying to conceive.
• Patients with suspected or confirmed cirrhosis (as assessed by clinical, radiological or histological criteria).
• Use of particular medications, including:
• Systemic antibiotics within the six weeks prior to study enrolment.
• Immunosuppression that may influence risks related to FMT (including - but not limited to: use of corticosteroids within eight weeks of intervention; use of cytotoxic chemotherapy; use of azathioprine, tacrolimus, mycophenolate mofetil and/or immunosuppressive biologic therapy, e.g. infliximab).
• Use of GLP-1 agonists.
• Patients not expected to survive the duration of the study's follow-up (six months).
• Swallowing difficulties that may preclude safe use of FMT capsules, including oral-motor dyscoordination.
• Alcohol consumption \> 20g/ day.
• Any active cancer (including treatment within the past six months).
• Active infection at the point of recruitment, including COVID-19 infection.
• Prior receipt of a liver transplant.
• BMI \< 23 in Asian potential participants and BMI \< 25 in Caucasians.
• Advanced chronic kidney disease (eGFR \< 30 ml/min).

Sponsors & Collaborators

• Imperial College London: lead
• King's College London: collaborator

Study Sites (1)

Division of Digestive Diseases/ Liver Unit, St Mary's Hospital Campus, Imperial College London

London, W2 1NY, United Kingdom

Location

Related Publications (1)

• Aghara H, Patel M, Chadha P, Parwani K, Chaturvedi R, Mandal P. Unraveling the Gut-Liver-Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches. Mediators Inflamm. 2025 Jun 18;2025:6733477. doi: 10.1155/mi/6733477. eCollection 2025.

  PMID: 40568349 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Pinelopi Manousou, MD PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Human participants with NAFLD and fibrosis

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: September 6, 2023
• Study Start: July 20, 2021
• Primary Completion: September 29, 2023
• Study Completion: October 31, 2023
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)