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Rifaximin in Fatty Liver Disease (RiFL)

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ClinicalTrials.gov Identifier: NCT01355575
Recruitment Status : Terminated (Review of primary endpoint data by study Investigators concluded no further patients required.)
First Posted : May 18, 2011
Last Update Posted : October 17, 2012
Sponsor:
Collaborator:
National Health Service, United Kingdom
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

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 or disease Intervention/treatment Phase
Nonalcoholic Fatty Liver Disease NAFLD Nonalcoholic Steatohepatitis Drug: Rifaximin Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (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)?
Study Start Date : May 2011
Actual Primary Completion Date : September 2012
Actual Study Completion Date : September 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases
Drug Information available for: Rifaximin
U.S. FDA Resources

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. Change in serum ALT levels [ Time Frame: 6 weeks therapy ]
    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 :
  1. Change in insulin resistance [ Time Frame: 6 weeks of therapy ]
    Hepatic and systemic insulin resistance assessed using the hyperinsulinaemic euglycaemic clamp method

  2. Change in hepatic triglyceride content [ Time Frame: 6 weeks of therapy ]
    In vivo proton magnetic resonance spectroscopy (1H MRS) to derive a T2-corrected triglyceride to water ratio



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01355575     History of Changes
Other Study ID Numbers: 2010-021515-17
2010-021515-17 ( EudraCT Number )
10/H0711/58 ( Other Identifier: Research Ethics Committee )
45706 ( Other Identifier: Imperial Joint Research Office )
First Posted: May 18, 2011    Key Record Dates
Last Update Posted: October 17, 2012
Last Verified: October 2012

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

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Rifaximin
Rifamycins
Anti-Infective Agents
Gastrointestinal Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents