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

NCT01951209 | Terminated

• 1 other identifier: 01478
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cirrhosis; Chronic Hepatitis C

Keywords

Human; Hepatitis C; Cirrhosis; B-cell; Rifaximin

Outcome Measures

Primary Outcomes (1)

• Change in CD27+ B-cell frequency

  Week 0 (Baseline) to Week 12

Secondary Outcomes (1)

• Change in basal B-cell activation

  Week 0 to Week 12

Other Outcomes (1)

• Change in circulating markers of bacterial translocation

  Week 0 to Week 12

Study Arms (2)

Rifaximin/Placebo

EXPERIMENTAL

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

Drug: Rifaximin; Drug: Placebo

Placebo/Rifaximin SSD

EXPERIMENTAL

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

Drug: Rifaximin; Drug: Placebo

Interventions

Rifaximin DRUG

550mg orally twice daily for 12 weeks

Also known as: Rifaximin (Xifaxan)

Placebo/Rifaximin SSD; Rifaximin/Placebo

Placebo DRUG

Matched placebo

Placebo/Rifaximin SSD; Rifaximin/Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• David E. Kaplan, MD MSc: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (1)

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 21932384 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Hepatitis C, Chronic; Hepatitis C; Fibrosis

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• David E Kaplan, MD, MSc

  Corporal Michael J. Crescenz VA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: GI Staff Physician

Study Record Dates

• First Submitted: September 20, 2013
• First Posted: September 26, 2013
• Study Start: November 17, 2016
• Primary Completion: November 17, 2016
• Study Completion: June 12, 2017
• Last Updated: March 11, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)