Rifaximin in Fatty Liver Disease

NCT01355575 | Terminated Phase 4 Results

• 3 other identifiers: 2010-021515-1710/H0711/5845706
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nonalcoholic Fatty Liver Disease; NAFLD; Nonalcoholic Steatohepatitis

Keywords

Microbiota; Insulin resistance; Bacterial endotoxin; Hepatic triglyceride; Inflammation

Outcome Measures

Primary Outcomes (1)

• Serum Alanine Aminotransferase (ALT) Levels

  Alanine aminotransferase (ALT) after 6-weeks of Rifaximin from baseline (end of treatment) and 12 weeks (6 weeks after end of treatment). ALT values reported are the values from 6-weeks Rifaximin treatment compared to baseline, and ALT values from 12 weeks (after 6 weeks of SoC) compared to baseline.

  Baseline, 6 weeks (end of treatment) and 12 weeks (6 weeks after end of treatment)

Secondary Outcomes (2)

• Insulin Resistance

  Baseline and 6 weeks (end of treatment)

• Hepatic Triglyceride Content

  Baseline and 6 weeks (end of treatment)

Study Arms (1)

Rifaximin for 6-weeks followed by 6-week observation period

EXPERIMENTAL

All patients receiving 6 weeks Rifaximin 400mg twice daily, followed by a 6 week observation period.

Drug: Rifaximin

Interventions

Rifaximin DRUG

Rifaximin tablet, oral administration, 400mg twice daily for 6 weeks.

Also known as: Xifaxan

Rifaximin for 6-weeks followed by 6-week observation period

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead
• National Health Service, United Kingdom: collaborator

Study Sites (1)

Liver Unit, St Mary's Hospital, Imperial College London

London, W2 1NY, United Kingdom

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Insulin Resistance; Inflammation

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr Jeremy Cobbold
• Organization: Imperial College London

jeremy.cobbold@ndm.ox.ac.uk

+44 1865228756

Study Officials

• Jeremy FL Cobbold, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Mark R Thursz, MD

  Imperial College London

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An open label pilot study with two phases (rather than 2 arms). All patients receiving 6 weeks Rifaximin 400mg twice daily, followed by a 6 week observation period.

Study Record Dates

• First Submitted: May 17, 2011
• First Posted: May 18, 2011
• Study Start: May 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 28, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)