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

Not Applicable

Completed

• Conditions: Fecal Microbiota Transplantation; Non-Alcoholic Fatty Liver Disease
• Interventions: Other: Faecal microbiota transplant

• Registration Number: NCT06024681
• Lead Sponsor: Imperial College London

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-20
• Study First Submitted: 2023-08-23
• Study First Submitted QC: 2023-08-29
• Study First Posted: 2023-09-06
• Primary Completion: 2023-09-29
• Study Completion: 2023-10-31
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NAFLD patients	Faecal microbiota transplant	Patients receiving capsulised FMT

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Changes in liver fat on FibroScan	16 weeks after initial FMT	Using CAP
Changes in liver fat on MRI	16 weeks after initial FMT	Using MRI-PDFF
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

Trial Locations

Locations (1)

Division of Digestive Diseases/ Liver Unit, St Mary's Hospital Campus, Imperial College London; 🇬🇧 London, United Kingdom