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

Sponsor

Imperial College London (Other)

Overall Status

Recruiting

CT.gov ID

NCT06024681

Collaborator

King's College London (Other)

Enrollment

Location

Arm

34.4

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease Fecal Microbiota Transplantation	Other: Faecal microbiota transplant	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Human participants with NAFLD and fibrosisHuman participants with NAFLD and fibrosis

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Jul 20, 2021

Anticipated Primary Completion Date :

Sep 29, 2023

Anticipated Study Completion Date :

May 31, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in faecal microbiome composition [24 weeks after initial FMT]
Using 16S rRNA gene sequencing and shotgun metagenomic sequencing
Change in gut microbial metabolite composition [24 weeks after initial FMT]
Using 1H-NMR and mass spectrometry

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18-75 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.

Exclusion Criteria:

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).
Chronic intestinal disease, including coeliac disease, cystic fibrosis, inflammatory bowel disease, irritable bowel syndrome, and chronic diarrhoea.
Prior bariatric surgery.
Patients unable to undergo MRI scans (e.g. due to the individual having metallic implants).