Rifaximin in Fatty Liver Disease (RiFL)

This study has been terminated.
(Review of primary endpoint data by study Investigators concluded no further patients required.)
Sponsor:
Collaborator:
National Health Service, United Kingdom
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01355575
First received: May 17, 2011
Last updated: October 16, 2012
Last verified: October 2012
  Purpose

TITLE Rifaximin in Fatty Liver Disease (RiFL) DESIGN Proof-of-principle, open-label, randomised, cross-over, controlled study HYPOTHESIS Reduction in gut flora by the antibiotic Rifaximin reduces hepatic inflammation in Non-Alcoholic Steatohepatitis (NASH).

AIMS To provide proof-of-concept data on the therapeutic potential of gut flora modification in NASH OUTCOME MEASURES

Primary:

• Change in serum ALT from baseline by 25 IU/L or to within normal range after 6 weeks of therapy

Secondary:

  • Change in intrahepatic triglyceride, estimated by in vivo proton magnetic resonance spectroscopy (1H MRS)
  • Change in hepatic insulin resistance, estimated by the hyperinsulinaemic euglycaemic clamp
  • Changes to the faecal bacterial microbiome assessed by faecal DNA pyrosequencing and fluorescent in-situ hybridisation (FISH)
  • Differences in urinary metabolic profiles as assessed by high-resolution proton nuclear magnetic resonance spectroscopy

POPULATION Patients with biopsy-confirmed non-alcoholic steatohepatitis and persistently raised serum aminotransferase levels

TREATMENT The non-absorbable antibiotic Rifaximin DURATION Study duration 18 months. Individual patients' participation 18 weeks, with clinical follow-up 3 months after the end of the study.


Condition Intervention Phase
Nonalcoholic Fatty Liver Disease
NAFLD
Nonalcoholic Steatohepatitis
Drug: Rifaximin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: RiFL:Rifaximin in Fatty Liver Disease. Does Modulation of Gut Microbiota Reduce Hepatic Inflammation in Non-Alcoholic Steatohepatitis (NASH)?

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Change in serum ALT levels [ Time Frame: 6 weeks therapy ] [ Designated as safety issue: No ]
    ALT value at timepoint post-therapy phase (6 weeks or 12 weeks) minus ALT value pre-therapy phase (0 weeks or 6 weeks)


Secondary Outcome Measures:
  • Change in insulin resistance [ Time Frame: 6 weeks of therapy ] [ Designated as safety issue: No ]
    Hepatic and systemic insulin resistance assessed using the hyperinsulinaemic euglycaemic clamp method

  • Change in hepatic triglyceride content [ Time Frame: 6 weeks of therapy ] [ Designated as safety issue: No ]
    In vivo proton magnetic resonance spectroscopy (1H MRS) to derive a T2-corrected triglyceride to water ratio


Enrollment: 15
Study Start Date: May 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: Rifaximin first then standard care
Rifaximin for 6 weeks in addition to standard care, followed by 12 weeks of standard care only.
Drug: Rifaximin
Rifaximin tablet, oral administration, 400mg twice daily for 6 weeks.
Experimental: B: Standard care first then Rifaximin
Standard care for 6 weeks then Rifaximin for 6 weeks in addition to standard care, followed by 6 weeks of standard care only.
Drug: Rifaximin
Rifaximin tablet, oral administration, 400mg twice daily for 6 weeks.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has provided written informed consent prior to screening
  • Men and women aged 18-70 years
  • Biopsy-proven NASH with or without mild to moderate fibrosis (fibrosis stage 0-3) in the preceding year
  • Persistently abnormal ALT on 2 occasions

Exclusion Criteria:

  • NAFLD with cirrhosis (fibrosis score 4)
  • Other causes of chronic liver disease

    • Viral hepatitis (HBV, HCV negative)
    • Alcohol intake >14units/week (women) or >21units/week (men)
    • Haemachromatosis (abnormal transferrin saturation, haemochromatosis genotyping)
  • Evidence of hepatic decompensation

    • Ascites
    • Hepatic encephalopathy
    • Abnormal total bilirubin (except patients with Gilbert's syndrome), albumin, prolonged prothrombin time, low platelets)
    • Oesophageal or gastric varices
  • Moderate or severe renal dysfunction (CKD3+, estimated GFR <60ml/min/1.73m2)
  • Hepatocellular carcinoma
  • Primary metabolic causes of hepatic steatosis (e.g. familial hypertriglyceridaemia, abetalipoproteinaemia)
  • Other malignancy
  • Pregnant or lactating women or women of childbearing potential unwilling/unable to use adequate contraceptive methods
  • Systemic inflammatory conditions

    • Arthritis
    • Connective tissue disorders
    • Inflammatory bowel disease
  • Myocardial infarction within 6 months
  • Stroke within 6 months
  • Bariatric surgery/ blind loop/ short bowel
  • Treatment known/suspected to change gut flora (e.g. systemic antibiotics, colestyramine, lactulose, polyethylene glycol) within 3 months
  • Treatment with drugs known to cause hepatic steatosis (e.g. corticosteroids, HAART, amiodarone, high dose oestrogens, tamoxifen) within 3 months
  • Initiation or major dose change of metformin, thiazolidinediones, biguanides, statins, fibrates, anti-obesity medications or insulin within 3 months of enrolment
  • Patients with allergy to Rifaximin or Rifamycin
  • Patients with a cardiac pacemaker, history of penetrating eye injury, metal foreign body or any other contra-indication to MRI scanning, as specified in the local MRI safety checklist
  • Any other clinical, social or psychological issues which, in the opinion of the investigators may preclude satisfactory completion of the study protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355575

Locations
United Kingdom
Liver Unit, St Mary's Hospital, Imperial College London
London, United Kingdom, W2 1NY
Sponsors and Collaborators
Imperial College London
National Health Service, United Kingdom
Investigators
Principal Investigator: Jeremy FL Cobbold, PhD Imperial College London
Study Chair: Mark R Thursz, MD Imperial College London
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01355575     History of Changes
Other Study ID Numbers: 2010-021515-17, 2010-021515-17, 10/H0711/58, 45706
Study First Received: May 17, 2011
Last Updated: October 16, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Microbiota
Insulin resistance
Bacterial endotoxin
Hepatic triglyceride
Inflammation

Additional relevant MeSH terms:
Fatty Liver
Inflammation
Liver Diseases
Digestive System Diseases
Pathologic Processes
Rifaximin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 26, 2014