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

NCT ID: NCT01951209

Last Updated: 2021-03-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-17
• Study Completion Date: 2017-06-12

Brief 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.

Detailed Description

We intend to enroll 18 patients with cirrhosis who do not have hepatic encephalopathy to prospectively evaluate the impact of rifaximin on B-cell phenotype and function. We plan to employ a randomized, double-masked, prospective crossover design to minimize bias. Subjects will be randomized to receive either rifaximin SSD 80mg or a matched placebo once daily for 12 weeks then crossed over to opposite therapy for 12 weeks. Serum and lymphocytes will be collected at baseline and every 4 weeks for in vitro assessment markers of gut microbial translocation and B-cell assays. Stool will be collected at baseline and every 12 weeks for future evaluation of changes of the gut microbiome.

Conditions

Liver Cirrhosis; Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Rifaximin/Placebo

Rifaximin 550mg po bid for 12 weeks followed by crossover to matched placebo po bid x 12 weeks

Group Type: EXPERIMENTAL

Rifaximin

Intervention Type: DRUG

550mg orally twice daily for 12 weeks

Placebo

Intervention Type: DRUG

Matched placebo

Placebo/Rifaximin SSD

Matched placebo po bid for 12 weeks followed by crossover to Rifaximin 550mg po bid x 12 weeks

Group Type: EXPERIMENTAL

Rifaximin

Intervention Type: DRUG

550mg orally twice daily for 12 weeks

Placebo

Intervention Type: DRUG

Matched placebo

Interventions

Rifaximin

550mg orally twice daily for 12 weeks

Intervention Type: DRUG

Placebo

Matched placebo

Intervention Type: DRUG

Other Intervention Names

Rifaximin (Xifaxan)

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role: collaborator

David E. Kaplan, MD MSc

FED

Sponsor Role: lead

Responsible Party

David E. Kaplan, MD MSc

GI Staff Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David E Kaplan, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Corporal Michael J. Crescenz VA Medical Center

Locations

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, United States

Countries

United States

References

Doi H, Iyer TK, Carpenter E, Li H, Chang KM, Vonderheide RH, Kaplan DE. Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-positive B-cell population. Hepatology. 2012 Mar;55(3):709-19. doi: 10.1002/hep.24689. Epub 2012 Jan 19.

Reference Type: BACKGROUND

PMID: 21932384 (View on PubMed)

Other Identifiers

01478

Identifier Type: -

Identifier Source: org_study_id