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

Investigating the Impact of Faecal Microbiota Transplant on the Clinical Phenome of Patients With Non-alcoholic Fatty Liver Disease and Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Fatty Liver Disease; Fecal Microbiota Transplantation
• Intervention / Treatment: Other: Faecal microbiota transplant

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1NY
    • Division of Digestive Diseases/ Liver Unit, St Mary's Hospital Campus, Imperial College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18-75 years of age.
2. Previously-diagnosed NAFLD, with predicted fibrosis based upon non-invasive assessment with FibroScan (i.e. liver stiffness measurement (LSM) > 8kPa).
3. 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).
4. Able to consent for themselves in English.

Exclusion Criteria:

1. Severe or life-threatening food allergy.
2. Pregnant or lactating women; or women trying to conceive.
3. Patients with suspected or confirmed cirrhosis (as assessed by clinical, radiological or histological criteria).

4. Use of particular medications, including:

   1. Systemic antibiotics within the six weeks prior to study enrolment.
   2. 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).
   3. Use of GLP-1 agonists.
5. Patients not expected to survive the duration of the study's follow-up (six months).
6. Swallowing difficulties that may preclude safe use of FMT capsules, including oral-motor dyscoordination.
7. Alcohol consumption > 20g/ day.
8. Any active cancer (including treatment within the past six months).
9. Active infection at the point of recruitment, including COVID-19 infection.
10. Prior receipt of a liver transplant.
11. BMI < 23 in Asian potential participants and BMI < 25 in Caucasians.
12. Advanced chronic kidney disease (eGFR < 30 ml/min).
13. Chronic intestinal disease, including coeliac disease, cystic fibrosis, inflammatory bowel disease, irritable bowel syndrome, and chronic diarrhoea.
14. Prior bariatric surgery.
15. Patients unable to undergo MRI scans (e.g. due to the individual having metallic implants).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAFLD patients; Patients receiving capsulised FMT	Other: Faecal microbiota transplant; Capsulised faecal microbiota transplant prepared from rationally selected donor, based upon donor metabolomic charateristics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in liver fat on MRI	Using MRI-PDFF	16 weeks after initial FMT
Changes in liver fat on FibroScan	Using CAP	16 weeks after initial FMT
Changes in liver stiffness on MRI	Using MRE	16 weeks after initial FMT
Changes in liver stiffness on FibroScan	Using transient elastography	16 weeks after initial FMT
Changes in HbA1c		24 weeks after initial FMT
Changes in insulin resistance	Combining fasting glucose and insulin levels to generate HOMA-IR	24 weeks after initial FMT
Changes in BMI	Through combination of measurement of weight in kilogram and height in metres, reporting BMI in kg/m^2	24 weeks after initial FMT
Changes in lipid metabolism	Serum lipid profile	24 weeks after initial FMT

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: King's College London
• Investigators: Principal Investigator: Pinelopi Manousou, MD PhD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): September 29, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Metabolomics; NAFLD; Gut microbiome
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ICL_21SM6787; 296522 (Other Identifier: IRAS); 21/LO/0454 (Other Identifier: REC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only anonymised microbiome and metabolome data will be shared with other researchers via open access repositories

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No