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

• ClinicalTrials.gov Identifier: NCT06024681
• Recruitment Status: Completed
• First Posted: September 6, 2023
• Last Update Posted: March 6, 2024
• Sponsor: Imperial College London
• Collaborator: King's College London
• Information provided by (Responsible Party): Imperial College London

Tracking Information

• First Submitted Date: August 23, 2023
• First Posted Date: September 6, 2023
• Last Update Posted Date: March 6, 2024
• Actual Study Start Date: July 20, 2021
• Actual Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 29, 2023)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 29, 2023)

• Changes in liver fat on MRI [ Time Frame: 16 weeks after initial FMT ]
  Using MRI-PDFF
• Changes in liver fat on FibroScan [ Time Frame: 16 weeks after initial FMT ]
  Using CAP
• Changes in liver stiffness on MRI [ Time Frame: 16 weeks after initial FMT ]
  Using MRE
• Changes in liver stiffness on FibroScan [ Time Frame: 16 weeks after initial FMT ]
  Using transient elastography
• Changes in HbA1c [ Time Frame: 24 weeks after initial FMT ]
• Changes in insulin resistance [ Time Frame: 24 weeks after initial FMT ]
  Combining fasting glucose and insulin levels to generate HOMA-IR
• Changes in BMI [ Time Frame: 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 [ Time Frame: 24 weeks after initial FMT ]
  Serum lipid profile

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Human participants with NAFLD and fibrosis

Masking: None (Open Label)
Primary Purpose: Basic Science

Condition

• Non-Alcoholic Fatty Liver Disease
• Fecal Microbiota Transplantation

Intervention

Other: Faecal microbiota transplant

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

Study Arms

Experimental: NAFLD patients

Patients receiving capsulised FMT

Intervention: Other: Faecal microbiota transplant

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 29, 2023): 16
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 31, 2023
• Actual Primary Completion Date: September 29, 2023 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT06024681
• Other Study ID Numbers: ICL_21SM6787; 296522 ( Other Identifier: IRAS ); 21/LO/0454 ( Other Identifier: REC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Only anonymised microbiome and metabolome data will be shared with other researchers via open access repositories

• Current Responsible Party: Imperial College London
• Original Responsible Party: Same as current
• Current Study Sponsor: Imperial College London
• Original Study Sponsor: Same as current
• Collaborators: King's College London

Investigators

• Principal Investigator: Pinelopi Manousou, MD PhD; Imperial College London

• PRS Account: Imperial College London
• Verification Date: March 2024