Pilot Study Of The Effect Of Rifaximin On B-Cell Dysregulation In Cirrhosis

• Status: Terminated
• Trial end date: 2017-06-12
• Target enrollment: 0
• Participant gender: All

Summary

Hepatitis C is the leading cause of chronic liver disease and cirrhosis in United States veterans. Cirrhosis is associated with impaired antibody responses and increased risk of bacterial infections. We have recently identified that cirrhosis is associated with abnormalities of memory B-cells, cells that make antibodies and help protect against bacterial infections. We have identified that chemicals associated with gut bacteria might play a role in causing these B-cell abnormalities. It is well known that gut bacteria have increased access to the blood in individuals with cirrhosis, a process called bacterial translocation. We hypothesize that reducing bacteria counts in the gut by using poorly-absorbed antibiotics (also known as selective gut decontamination) will partially reverse losses of memory B-cells in cirrhosis by reducing bacterial translocation.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: David E. Kaplan, MD MSc
• Collaborators: Bausch Health Americas, Inc.; Valeant Pharmaceuticals International, Inc.
• Treatments: Rifamycins; Rifaximin

Criteria

Inclusion Criteria:

• Current or prior chronic Hepatitis C infection as documented by detectable HCV RNA in prior 5 years

• Child-Turcotte-Pugh stage A5-B8. Cirrhosis diagnosis may be based on either histological criteria (an previous liver biopsy showing F4/4 or F5-6/6 fibrosis) or clinical criteria (nodular liver on abdominal imaging, splenomegaly, thrombocytopenia, spider telangiectasias, palmar erythema, ascites, varices).

• Platelet count < 175,000/ul

• Subject capable of giving informed consent

Exclusion Criteria:

• Active alcohol use > 20g/d

• Current or planned (within following 6 months) antiviral therapy for hepatitis C

• HIV co-infection

• Diagnosis of overt hepatic encephalopathy

• Current lactulose use

• Exposure to rifaximin, rifampin or rifabutin within 12 months

• History of C. difficile colitis

• History of adverse drug reaction or sensitivity to rifaximin, rifampin or rifabutin or any inactive components of rifaximin

• Pregnancy

• Anemia with hemoglobin < 10g/dl or hematocrit < 30%

• Chronic kidney disease with creatinine > 2.1mg/dl

• Total bilirubin > 3.0g/dl

• Active non-hepatic medical conditions such as congestive heart failure, chronic lung disease requiring oxygen, coronary artery disease with unstable angina

• Requirement for chronic immunosuppressive therapy such as corticosteroids, cyclophosphamide, azathioprine, TNF-alpha antagonists

• Chronic autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis

• Post-liver transplantation status or anticipated liver transplantation within 6 months.

• Systemic antimicrobial exposure within 30 days of planned Visit 1