Rifaximin Modify the Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)

Could Rifaximin Modify the Pathogenesis of NAFLD? AMulticenter, Randomized, Double-Blind, Placebo-Controlled Trial

In this multicentric, double-blind, randomized,placebo-controlled study, the investigators hypothesized that rifaximin might act on Gram-negative bacteria and intestinal bacterial overgrowth(IBO) thereby inhibiting lipopolysaccharides(LPS)-mediated proinflammatory cytokine production. This work evaluates the efficacy of 6 months administration of rifaximin in NAFLD patients.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Rifaximin group 1

Detailed Description

The investigators aimed to study the effect of rifaximin on NASH. 50 patients with biopsy-proven NASH were enrolled in this double-blind, randomized,placebo-controlled study. BMI, AST, ALT, gamma glutamyl transferase (γ-GGT), lipid profile, homeostatic model assessment (HOMA), serum endotoxin, Toll-like receptor 4 (TlR4), interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α) and cytokeratin-18 (CK-18) levels were measured before and after a 6 month administration of rifaximin (1100mg/day, 550 mg tablets 1 × 2 before meals).

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Egypt
  • Mansoura, Egypt
    • Nasser H Mousa,MD,mousa_medic@yahoo.com. +201227029213

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

In this multicentric, double-blind, randomized,placebo-controlled study, we enrolled consecutively 1072 participants with hepatitis irrespective to their etiologies referred to the Tropical Medicine and Internal Medicine Departments (Mansoura University), Tropical Medicine Department (Zagazig University), and Internal Medicine and Endemic Diseases and Gastroenterology Departments (Aswan University)from May 2012 to October 2016. All participants underwent to the following appraisal: physical and biochemical examination, complete history taking, abdominal ultrasound, and percutaneous ultrasound liver biopsy.

Description

Inclusion Criteria:

1. women or men aged 18-65 years.
2. biopsy-proven NASH without or with mild to moderate fibrosis (fibrosis stage 0-3)in the preceding year.
3. persistently abnormal ALT on 2 occasions.
4. participants have provided written informed consent before screening.
5. all patients counseled about the standard of care treatment (e.g., diet andexercise).
6. Strict requirements for weight stability between the time of biopsy and study entry.

Exclusion Criteria:

1. Cirrhotic NAFLD (METAVIR stage 4).
2. Combined viral hepatitis B and C infection.
3. increased alcohol intake (>20 g/day) and hypothyroidism.
4. co-existence of another type of biliary tract or pancreatic or liver diseases
5. lactating or pregnant women.
6. allergy to rifamycin or rifaximin.
7. systemic inflammatory conditions (e.g. Connective tissue diseases and inflammatory bowel diseases).
8. bariatric surgery and blind loop.
9. evidence of hepatic decompensation (ascites, hepatic encephalopathy, and varices),
10. history of myocardial infarction and/ or stroke within 6 months.
11. drugs that alter the gut flora e.g. Lactulose, systemic antibiotic, cholestyramine within three months, (l) cancers especially HCC, and (m)patients with renal impairment (estimated GFR <60ml/min/1.73m2).

(n) Major dose change orintiation of biguanides, metformin, thiazolidinediones, insulin, fibrates, statins, and anti-obesity medications within three months before the onset of the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Rifaxmin group	Drug: Rifaximin group 1; Rifaximin: 1100mg/day, 550 mg tablets 1 × 2 before meals
2; placebo group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum ALT	U/l	6 months
serum endotoxins	EU/ml	6 months
TLR-4	ng/ml	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Glucose	mg/dl	6 months
, Insulin,	μIU/ml	6 months
CK-18,TNF-α, IL-6, IL 10	pg/ml	6 months

Collaborators and Investigators

• Sponsor: Mansoura University

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: July 29, 2016
• First Submitted That Met QC Criteria: August 25, 2016
• First Posted (Estimate): August 30, 2016

Study Record Updates

• Last Update Posted (Actual): August 11, 2017
• Last Update Submitted That Met QC Criteria: August 9, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: NAFLD; Rifaximin; Endotoxin and Homeostatic Model Assessment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: R/16.02.80

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO