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Sponsors and Collaborators: |
Weill Medical College of Cornell University Salix Pharmaceuticals |
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Information provided by: | Weill Medical College of Cornell University |
ClinicalTrials.gov Identifier: | NCT00281502 |
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:
Condition | Intervention | Phase |
---|---|---|
Hepatic Encephalopathy Hepatitis C Liver Cirrhosis |
Drug: Rifaximin (drug) |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study |
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 |
Estimated Enrollment: | 50 |
Study Start Date: | December 2005 |
Estimated Study Completion Date: | December 2007 |
Hepatic encephalopathy is a frequent and occasionally refractory complication of cirrhosis and is associated with impaired quality of life. Its severity may not correlate with other parameters of liver dysfunction. Although multiple pathogenic mechanisms for the condition have been proposed, most include the participation of bacterial toxins, especially ammonia, produced in the gastrointestinal tract. Treatment options for hepatic encephalopathy at this time are limited to lactulose and neomycin. Lactulose is frequently poorly tolerated, and many patients are non-compliant with its use. In patients with renal insufficiency in whom hepatic encephalopathy is frequently problematic, use of neomycin is contraindicated due to ototoxicity and nephrotoxicity.
Autonomic dysfunction is common in patients with cirrhosis and could contribute to the development of hepatic encephalopathy by impairment of intestinal motility, leading to bacterial overgrowth and colonic inertia.
The following questions will be addressed:
A. Is impaired intestinal transit and bacterial overgrowth associated with the presence and severity of hepatic encephalopathy?
50 patients will undergo a detailed clinical evaluation for severity of liver disease, hepatic encephalopathy and assessment of intestinal transit and bacterial overgrowth with radiographic marker study and breath test analysis. Multivariate analysis will then be performed to determine the relationship of intestinal transit and evidence of bacterial overgrowth with the presence and severity of hepatic encephalopathy.
B. Does treatment with rifaximin improve bacterial overgrowth and hepatic encephalopathy?
20 patients from the above population with significant encephalopathy will be randomized to receive either rifaximin or placebo. Post-treatment evaluation for severity of hepatic encephalopathy and breath test analysis for bacterial overgrowth will then be performed. The effect of treatment on changes in hepatic encephalopathy and bacterial overgrowth and the relationship between changes in bacterial overgrowth and severity of hepatic encephalopathy will also be assessed.
Phase A Endpoints: Degree of bacterial overgrowth and its correlation with the grade of hepatic encephalopathy (if present).
Phase B Endpoints: To demonstrate improvement in degree of HE with treatment of Rifaximin
Efficacy Endpoints The primary efficacy endpoint for Phase B of the study will be the change from baseline in the proportion of patients with no HE, minimal HE (no symptoms, abnormal psychometric testing), mild persistent HE (mild symptoms), and persistent Stage II HE (presence of asterixis, history of hospitalization for spontaneous Stage III or IV HE).
Secondary efficacy endpoints for Phase B will be the following:
To demonstrate improvement in intestinal transit time for patients (based on Lactulose Hydrogen Breath Test) To demonstrate improvement in bacterial overgrowth, improved insomnia, flatulence, and quality of life.
To demonstrate that rifaximin improved patients’ symptoms of insomnia, flatulence, and quality of life measure with the degree of bacterial overload and the impaired intestinal transit time.
Ages Eligible for Study: | 18 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Phase A Inclusion Criteria:
Phase A Exclusion Criteria:
Phase B Inclusion Criteria
Phase B Exclusion Criteria
Contact: Sam Sigal, M.D. | 212 746-4129 | shs2015@med.cornell.edu |
Contact: Elvia Saravia, B.A. | 212 746-5551 | eds2011@med.cornell.edu |
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 | |
Contact: Elvia Saravia, B.A. 212 746-5551 eds2011@med.cornell.edu | |
Principal Investigator: Sam Sigal, M.D. | |
Sub-Investigator: Brian P. Bosworth, M.D. | |
Sub-Investigator: Michael Schilsky, M.D. |
Principal Investigator: | Sam Sigal, M.D. | Weill Medical College of Cornell University |
Study ID Numbers: | Salix-RifaxPSE-BactOvrGrwth-01 |
Study First Received: | January 20, 2006 |
Last Updated: | July 19, 2007 |
ClinicalTrials.gov Identifier: | NCT00281502 |
Health Authority: | United States: Food and Drug Administration |
Hepatic Encephalopathy Hepatitis C Liver Cirrhosis Bacterial Overgrowth |
Liver Diseases Neurotoxicity Syndromes Fibrosis Brain Damage, Chronic Disorders of Environmental Origin Hepatitis, Viral, Human Liver Cirrhosis Brain Diseases Signs and Symptoms Mental Disorders Hepatitis C Brain Injuries Dementia Neurobehavioral Manifestations Hepatic Insufficiency |
Delirium Liver Failure Metabolic Diseases Neurotoxicity syndromes Poisoning Central Nervous System Diseases Confusion Cognition Disorders Encephalitis Hepatitis Virus Diseases Hepatic Encephalopathy Delirium, Dementia, Amnestic, Cognitive Disorders Digestive System Diseases Central Nervous System Infections |
Anti-Infective Agents RNA Virus Infections Pathologic Processes Flaviviridae Infections Therapeutic Uses |
Nervous System Diseases Gastrointestinal Agents Central Nervous System Viral Diseases Pharmacologic Actions |