Rifaximin in Minimal Hepatic Encephalopathy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether alteration of gut flora with rifaximin can lead to improvement in driving performance, psychometric test performance, and quality of life in patients with minimal hepatic encephalopathy (MHE) and cirrhosis in a randomized, blinded, placebo-controlled trial.

Official Title
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Effect of Rifaximin on Driving Performance, Psychometric Test Performance and Quality of Life in Cirrhotic Patients With Minimal Hepatic Encephalopathy: Randomized, Double-blind, Placebo-controlled Trial.

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: Rifaximin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years Cirrhosis diagnosed on clinical grounds MHE diagnosed by abnormalities in a psychometric battery (NCT-A, NCT-B, ICT BDT and DST impaired beyond 2 standard deviations of known control values on any of the above 3 tests will be considered to have MHE) Current drivers (valid driving license and driving at least 20 miles/week) All women of child-bearing potential will be required to use effective contraception Exclusion Criteria: Current or recent (< 6 month) use of alcohol (AUDIT questionnaire will be used; any cirrhotic with a value of > 0 will be excluded) and a positive blood alcohol level Use of antibiotics within last 6 weeks Allergy to rifaximin, rifabutin, rifampin, or rifapentine Infection or gastrointestinal hemorrhage within the last 6 weeks Renal insufficiency Hepatocellular carcinoma Psychoactive drug use, including interferon concurrently Non-drivers and those who drive less than 20 miles/week Pregnancy and breastfeeding Excluding patients with OHE: Detailed neurological examination to check for dysarthria, asterixis, ataxia and disorientation Detailed history-taking from friends/relatives only after taking the patient's permission Mini-mental status examination > 25 Episode of overt (clinical hepatic encephalopathy) within 6 months Current treatment with lactulose, rifaximin, zinc, or metronidazole

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Will be given placebo and follow the exact procedures as the experimental section | Drug: placebo<br>* same as the experimental arm<br>|
| Experimental: Drug<br> | Drug: Rifaximin<br>* 550mg BID rifaximin for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Driving Performance | Total driving errors at the end of drug/placebo. Minimum is zero, maximum is not defined. Higher number indicates greater errors. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychometric Test Performance | Z score of combined cognitive tests at end of rifaximin/placebo; higher scores indicate better psychometric test performance | 8 weeks | 
| Total Sickness Impact Profile Score | Total score ranging from 0 through >100 at the end of drug/placebo. Higher score indicates worse QOL | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Minimal hepatic encephalopathy