Rifaximin in Fatty Liver Disease

• Status: Terminated
• Trial end date: 2012-09-01
• Target enrollment: 0
• Participant gender: All

Summary

TITLE Rifaximin in Fatty Liver Disease (RiFL) DESIGN Open-label pilot 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 Rifaximin 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 This was an open-label study of Rifaximin (Normix, Alfa Wasserman S.p.A, Bologna, Italy) 400mg twice daily for six weeks followed by a further six weeks observation period during which patients received standard care.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Imperial College London
• Collaborator: National Health Service, United Kingdom
• Treatments: Rifamycins; Rifaximin

Criteria

Inclusion Criteria:

• Subject has provided written informed consent prior to screening

• Men and women aged 18-70 years

• With non-alcoholic steatohepatitis histologically-proven, as evidenced by the presence of all of: steatosis, hepatocyte ballooning and lobular inflammation, and scored according to Kleiner(18) by a single experienced histopathologist (RDG) within the previous year, with or without mild to moderate fibrosis (stage 0-3/4)

• With persistently elevated alanine aminotransferase (ALT) values on at least two occasions in the three months prior to recruitment

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