Clinical trial NCT06024681: Impact of FMT on the Phenome in Patients With NAFLD and Fibrosis
Official title: Investigating the Impact of Faecal Microbiota Transplant on the Clinical Phenome of Patients With Non-alcoholic Fatty Liver Disease and Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Fecal Microbiota Transplantation
Keywords: NAFLD
Gut microbiome
Metabolomics
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: King's College London
First posted: 2023-09-06
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Human participants with NAFLD and fibrosis
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change in faecal microbiome composition
timeFrame: 24 weeks after initial FMT
measure: Change in gut microbial metabolite composition
timeFrame: 24 weeks after initial FMT
Secondary outcomes:
measure: Changes in liver fat on MRI
timeFrame: 16 weeks after initial FMT
measure: Changes in liver fat on FibroScan
timeFrame: 16 weeks after initial FMT
measure: Changes in liver stiffness on MRI
timeFrame: 16 weeks after initial FMT
measure: Changes in liver stiffness on FibroScan
timeFrame: 16 weeks after initial FMT
measure: Changes in HbA1c
timeFrame: 24 weeks after initial FMT
measure: Changes in insulin resistance
timeFrame: 24 weeks after initial FMT
measure: Changes in BMI
timeFrame: 24 weeks after initial FMT
measure: Changes in lipid metabolism
timeFrame: 24 weeks after initial FMT
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Division of Digestive Diseases/ Liver Unit, St Mary's Hospital Campus, Imperial College London
Study officials:
affiliation: Imperial College London
name: Pinelopi Manousou, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: