Rifaximin in Fatty Liver Disease (RiFL)
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|ClinicalTrials.gov Identifier: NCT01355575|
Recruitment Status : Terminated (Primary endpoint data review concluded no further patients required.)
First Posted : May 18, 2011
Results First Posted : September 4, 2020
Last Update Posted : October 28, 2020
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
• Change in serum ALT from baseline by 25 IU/L or to within normal range after 6 weeks of Rifaximin therapy
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Nonalcoholic Fatty Liver Disease NAFLD Nonalcoholic Steatohepatitis||Drug: Rifaximin||Phase 4|
STUDY OBJECTIVES The primary endpoint was change in ALT after 6 weeks of Rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinaemic euglycaemic clamp.
STUDY DESIGN 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. Compliance with treatment was checked by collection of empty blister packs. Subjects were asked to provide a structured dietary and lifestyle history as previously described (Williams HR, Cox IJ, Walker DG, North BV, Patel VM, Marshall SE, Jewell DP, et al. Characterization of inflammatory bowel disease with urinary metabolic profiling. Am J Gastroenterol 2009;104:1435-1444). The primary endpoint was change in ALT after 6 weeks' Rifaximin therapy. Secondary endpoints were change in hepatic and whole-body insulin sensitivity assessed by the two-stage hyperinsulinaemic euglycaemic clamp and change in hepatic triglyceride content assessed by proton nuclear magnetic resonance spectroscopy at 6 weeks from baseline. Serum ALT, biochemistry and anthropometrics were also measured at 12 weeks to look for longer-term effects. Stool microbiota, urinary metabolic profile and serum cytokine profile were measured before and after intervention.
INCLUSION CRITERIA Male and female patients were eligible for inclusion if aged between 18 and 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) and with persistently elevated alanine aminotransferase (ALT) values on at least two occasions in the three months prior to recruitment.
EXCLUSION CRITERIA Patients were excluded if there was histological evidence of cirrhosis; hepatic decompensation; regular alcohol consumption exceeding 14 units/week (16g ethanol/day) for a woman or 21 units/week (24g ethanol/day) for a man; evidence of viral, autoimmune or other metabolic liver disease on a chronic liver disease screen; a history of malignancy or systemic inflammatory conditions; myocardial infarction or cerebrovascular events in the preceding 6 months; a history of bariatric surgery, blind loop or short bowel; use of any treatment known or suspected to change bowel flora within 3 months of enrolment; initiation or major dose change of metformin, thiazolinediones, biguanides, statins, fibrates, anti-obesity medications or insulin within 3 months of enrolment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||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.|
|Masking:||None (Open Label)|
|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|
Experimental: Rifaximin for 6-weeks followed by 6-week observation period
All patients receiving 6 weeks Rifaximin 400mg twice daily, followed by a 6 week observation period.
Rifaximin tablet, oral administration, 400mg twice daily for 6 weeks.
Other Name: Xifaxan
- Serum Alanine Aminotransferase (ALT) Levels [ Time Frame: Baseline, 6 weeks (end of treatment) and 12 weeks (6 weeks after end of treatment) ]
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.
- Insulin Resistance [ Time Frame: Baseline and 6 weeks (end of treatment) ]
Hepatic and systemic insulin resistance assessed using the hyperinsulinaemic euglycaemic clamp method.
Measured in % Suppression of Endogenous Glucose Production (SEGP). Values reported are the value from baseline and value from 6 weeks Rifaximin treatment.
- Hepatic Triglyceride Content [ Time Frame: Baseline and 6 weeks (end of treatment) ]
In vivo proton magnetic resonance spectroscopy (1H MRS) to derive a T2-corrected triglyceride to water ratio (hepatic lipid content- intra-hepatocellular lipid (IHCL)).
The values reported are the values from baseline and the values from 6 weeks Rifaximin treatment.
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
|Liver Unit, St Mary's Hospital, Imperial College London|
|London, United Kingdom, W2 1NY|
|Principal Investigator:||Jeremy FL Cobbold, PhD||Imperial College London|
|Study Chair:||Mark R Thursz, MD||Imperial College London|