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

NCT00281502 | Unknown Phase 2

• 1 other identifier: Salix-RifaxPSE-BactOvrGrwth-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hepatic Encephalopathy; Hepatitis C; Liver Cirrhosis

Keywords

Hepatic Encephalopathy; Hepatitis C; Liver Cirrhosis; Bacterial Overgrowth

Outcome Measures

Primary Outcomes (2)

• Phase A: Degree of bacterial overgrowth and its correlation with the grade of hepatic encephalopathy (if present)

  3 months

• Phase B: Improvement in the psychometric scores and proportion of patients who change of HE stage

  3 months

Secondary Outcomes (5)

• Improved Intestinal transit time

  3 months

• Improvement in bacterial overgrowth

  3 months

• Improved insomnia

  3 months

• Improved flatulence

  3 months

• Improved quality of life.

  3 months

Interventions

Rifaximin (drug) DRUG

Rifaximin 400mg three (3) times daily

Also known as: Xifaxan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (1)

New York Presbyterian Hospital: Weill Medical College of Cornell University

New York, New York, 10021, United States

RECRUITING

Related Publications (6)

• Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002 Mar;35(3):716-21. doi: 10.1053/jhep.2002.31250.

  PMID: 11870389 BACKGROUND

• Arguedas MR, DeLawrence TG, McGuire BM. Influence of hepatic encephalopathy on health-related quality of life in patients with cirrhosis. Dig Dis Sci. 2003 Aug;48(8):1622-6. doi: 10.1023/a:1024784327783.

  PMID: 12924658 BACKGROUND

• Groeneweg M, Moerland W, Quero JC, Hop WC, Krabbe PF, Schalm SW. Screening of subclinical hepatic encephalopathy. J Hepatol. 2000 May;32(5):748-53. doi: 10.1016/s0168-8278(00)80243-3.

  PMID: 10845661 BACKGROUND

• Groeneweg M, Quero JC, De Bruijn I, Hartmann IJ, Essink-bot ML, Hop WC, Schalm SW. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology. 1998 Jul;28(1):45-9. doi: 10.1002/hep.510280108.

  PMID: 9657095 BACKGROUND

• Amodio P, Del Piccolo F, Marchetti P, Angeli P, Iemmolo R, Caregaro L, Merkel C, Gerunda G, Gatta A. Clinical features and survivial of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests. Hepatology. 1999 Jun;29(6):1662-7. doi: 10.1002/hep.510290619.

  PMID: 10347105 BACKGROUND

• Bustamante J, Rimola A, Ventura PJ, Navasa M, Cirera I, Reggiardo V, Rodes J. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999 May;30(5):890-5. doi: 10.1016/s0168-8278(99)80144-5.

  PMID: 10365817 BACKGROUND

MeSH Terms

Conditions

Hepatic Encephalopathy; Hepatitis C; Liver Cirrhosis

Interventions

Rifaximin; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Fibrosis; 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

Study Officials

• Sam Sigal, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sam Sigal, M.D.

CONTACT

646 962-5483; shs2015@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 20, 2006
• First Posted: January 24, 2006
• Study Start: December 1, 2005
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: November 5, 2010

Record last verified: 2010-11

Locations

US (1)