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

March 8, 2021 updated by: David E. Kaplan, MD MSc

Prospective Pilot Study of the Effect of Rifaximin on B-Cell Dysregulation in Cirrhosis Due to Chronic Hepatitis C Infection

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Philadelphia VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rifaximin/Placebo
Rifaximin 550mg po bid for 12 weeks followed by crossover to matched placebo po bid x 12 weeks
Drug: Placebo
Matched placebo
Drug: Rifaximin
550mg orally twice daily for 12 weeks
Other Names:
  • Rifaximin (Xifaxan)
Experimental: Placebo/Rifaximin SSD
Matched placebo po bid for 12 weeks followed by crossover to Rifaximin 550mg po bid x 12 weeks
Drug: Placebo
Matched placebo
Drug: Rifaximin
550mg orally twice daily for 12 weeks
Other Names:
  • Rifaximin (Xifaxan)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in CD27+ B-cell frequency
Time Frame: Week 0 (Baseline) to Week 12
Week 0 (Baseline) to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in basal B-cell activation
Time Frame: Week 0 to Week 12
5 x 104/well B-cells negatively selected from normal donor PBMC will be cultured in 50% RPMI 1640/50% cirrhotic patient serum for 48 hours. After 48 hours, B-cells will be assessed for activation markers such as HLA-DR geometric mean fluorescence intensity.
Week 0 to Week 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in circulating markers of bacterial translocation
Time Frame: Week 0 to Week 12
Plasma samples will be studied for sCD14 by ELISA, bacterial DNA by rtPCR of 16S ribosomal RNA using established techniques, and Limulus Amebocyte Lysate Assay
Week 0 to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David E. Kaplan, MD MSc

Collaborators

Bausch Health Americas, Inc.

Investigators

  • Principal Investigator: David E Kaplan, MD, MSc, Corporal Michael J. Crescenz VA Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 17, 2016

Primary Completion (Actual)

November 17, 2016

Study Completion (Actual)

June 12, 2017

Study Registration Dates

First Submitted

September 20, 2013

First Submitted That Met QC Criteria

September 23, 2013

First Posted (Estimate)

September 26, 2013

Study Record Updates

Last Update Posted (Actual)

March 11, 2021

Last Update Submitted That Met QC Criteria

March 8, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01478

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Deidentified primary data will be made available for verification

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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