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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01951209
Recruitment Status : Active, not recruiting
First Posted : September 26, 2013
Last Update Posted : March 25, 2019
Bausch Health Americas, Inc.
Information provided by (Responsible Party):
David E. Kaplan, MD MSc, Corporal Michael J. Crescenz VA Medical Center

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.

Condition or disease Intervention/treatment Phase
Liver Cirrhosis Chronic Hepatitis C Drug: Rifaximin Drug: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Prospective Pilot Study of the Effect of Rifaximin on B-Cell Dysregulation in Cirrhosis Due to Chronic Hepatitis C Infection
Actual Study Start Date : August 2016
Actual Primary Completion Date : August 2018
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Rifaximin

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: Rifaximin
550mg orally twice daily for 12 weeks
Other Name: Rifaximin (Xifaxan)

Drug: Placebo
Matched placebo

Experimental: Placebo/Rifaximin SSD
Matched placebo po bid for 12 weeks followed by crossover to Rifaximin 550mg po bid x 12 weeks
Drug: Rifaximin
550mg orally twice daily for 12 weeks
Other Name: Rifaximin (Xifaxan)

Drug: Placebo
Matched placebo

Primary Outcome Measures :
  1. Change in CD27+ B-cell frequency [ Time Frame: Week 0 (Baseline) to Week 12 ]

Secondary Outcome Measures :
  1. 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.

Other Outcome Measures:
  1. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01951209

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United States, Pennsylvania
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
David E. Kaplan, MD MSc
Bausch Health Americas, Inc.
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Principal Investigator: David E Kaplan, MD, MSc Corporal Michael J. Crescenz VA Medical Center
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Responsible Party: David E. Kaplan, MD MSc, GI Staff Physician, Corporal Michael J. Crescenz VA Medical Center Identifier: NCT01951209    
Other Study ID Numbers: 01478
First Posted: September 26, 2013    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Deidentified primary data will be made available for verification
Keywords provided by David E. Kaplan, MD MSc, Corporal Michael J. Crescenz VA Medical Center:
Hepatitis C
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pathologic Processes
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents