The Role of Bacterial Overgrowth and Delayed Intestinal Transit in Hepatic Encephalopathy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by Weill Medical College of Cornell University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Salix Pharmaceuticals
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00281502
First received: January 20, 2006
Last updated: November 4, 2010
Last verified: November 2010
  Purpose

The study will be conducted in two phases. Phase A will evaluate the contribution of bacterial overgrowth and colonic inertia to development of Hepatic Encephalopathy (HE)in 50 ambulatory subjects with HE and hepatitis C cirrhosis. This phase will include a Screening and Evaluation Visit.

Phase B will evaluate the effect of rifaximin on bacterial outgrowth and severity of HE in 20 of the subjects enrolled in Phase A who have a somewhat greater degree of encephalopathy.

The purpose of this study is to evaluate the following:

  1. the relationship between bacterial overgrowth and the presence and severity of HE in patients with hepatitis C cirrhosis;
  2. the effectiveness and tolerability of rifaximin relative to placebo in treatment of HE associated with hepatitis C cirrhosis;
  3. the relationship between bacterial overgrowth and the presence and severity of HE before and after rifaximin treatment.

Condition Intervention Phase
Hepatic Encephalopathy
Hepatitis C
Liver Cirrhosis
Drug: Rifaximin (drug)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Role of Bacterial Overgrowth and Delayed Intestinal Transit in Hepatic Encephalopathy. Phase A: Breath Testing and Colonic Transit in Hepatic Encephalopathy. Phase B: A Randomized Double Blind, Placebo Controlled Trial of Rifaximin for Hepatic Encephalopathy

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Phase A: Degree of bacterial overgrowth and its correlation with the grade of hepatic encephalopathy (if present) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Phase B: Improvement in the psychometric scores and proportion of patients who change of HE stage [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improved Intestinal transit time [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Improvement in bacterial overgrowth [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Improved insomnia [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Improved flatulence [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Improved quality of life. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2005
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Rifaximin (drug)
    Rifaximin 400mg three (3) times daily
    Other Name: Xifaxan
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Phase A Inclusion Criteria:

  • Subject is 18 to 70 years of age, inclusive.
  • Subject has cirrhosis due to chronic HCV infection as documented by:
  • Subject has evidence of hepatic encephalopathy as evidenced by:
  • Neuro-psychometric Testing (Number Connection Test, Trails Test, etc.)
  • Subject is non-azotemic (creatinine <1.5mg/dL) and ambulatory at screening.
  • Subject has cirrhosis due to chronic HCV as documented by: pathologic or clinical and radiographic evidence of cirrhosis with a positive HCV RNA PCR level.

Phase A Exclusion Criteria:

  • Subject has received active interferon therapy within 2 weeks of enrollment.
  • Subject is pregnant or lactating.
  • Subject has a life expectancy of less than 100 days.
  • Subject has a history of alcohol abuse within 6 months of enrollment.
  • Subject has active gastrointestinal bleeding at time of enrollment.
  • Subject has used an agent that alters intestinal motility, eg, methadone, cholestyramine, tricyclic antidepressants.
  • Subject is unable to take oral medication.
  • Subject has used neomycin or other antibiotic within 2 weeks of enrollment or is actively using lactulose at time of enrollment.
  • Subject is taking or has hypersensitivity or allergy to rifaximin or rifampin.
  • Subject requires long term antibiotic therapy (eg, Lyme Disease, tuberculosis).
  • Subject has known or suspected alcohol abuse or illicit drug use within 1 year of enrollment.
  • Subject has participated in an investigational drug or device study within the 30 days prior to randomization.
  • Subject has received rifaximin within the last 30 days.
  • Subject has concomitant disease or condition that could interfere with, or for which treatment could interfere with the conduct of the study, or could in the opinion of the investigator increase the risk of AEs for the subject's participation in the study.
  • Subject is unwilling or unable to comply with the study protocol for any other reason.
  • Subject has been diagnosed with other forms of liver disease, including those with HIV and HBV co-infection, as determined by history, serological parameters, and histology when available.
  • Subject has been diagnosed with a major psychiatric illness, chronic renal and/or respiratory insufficiency, intercurrent infections, treatment with sedatives within 7 days of enrollment.
  • Subject shows presence of intestinal obstruction or inflammatory bowel disease, antacids or cathartics within the 12h before study start; antibiotics during 7 days before start of dosing; or treated with encephalopathy-causing agents.
  • Subjects with bad vision or neurological diseases since they could have difficulty completing the neuropsychological assessments.

Phase B Inclusion Criteria

  • Subject successfully participated in and continues to meet all eligibility criteria required in Phase A of the study based on completion of tests, Breath Tests, and Radiological Marker.
  • Subject has a Number Connection Test score >50 sec at time of enrollment.

Phase B Exclusion Criteria

  • A subject will not be eligible for inclusion in Phase B if (s)he meets any of the exclusion criteria for Phase A of the study.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00281502

Contacts
Contact: Sam Sigal, M.D. 646 962-5483 shs2015@med.cornell.edu

Locations
United States, New York
New York Presbyterian Hospital: Weill Medical College of Cornell University Recruiting
New York, New York, United States, 10021
Contact: Sam Sigal, M.D.    212-746-4129    shs2015@med.cornell.edu   
Principal Investigator: Sam Sigal, M.D.         
Sub-Investigator: Brian P. Bosworth, M.D.         
Sub-Investigator: Ilan Weisberg, M.D.         
Sponsors and Collaborators
Weill Medical College of Cornell University
Salix Pharmaceuticals
Investigators
Principal Investigator: Sam Sigal, M.D. Weill Medical College of Cornell University
  More Information

Publications:
Responsible Party: Sam Sigal, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00281502     History of Changes
Other Study ID Numbers: Salix-RifaxPSE-BactOvrGrwth-01
Study First Received: January 20, 2006
Last Updated: November 4, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
Hepatic Encephalopathy
Hepatitis C
Liver Cirrhosis
Bacterial Overgrowth

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Brain Diseases
Liver Cirrhosis
Hepatic Encephalopathy
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Brain Diseases, Metabolic
Metabolic Diseases
Rifaximin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 18, 2014