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Impact of an Antibiotic (Rifaximin) on Liver Scarring in HIV-Infected Patients With Liver Disease

This study is currently recruiting participants.
Verified October 2012 by Mount Sinai School of Medicine
Sponsor:
Collaborator:
Salix Pharmaceuticals
Information provided by (Responsible Party):
Douglas T. Dieterich, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01654939
First received: July 30, 2012
Last updated: October 24, 2012
Last verified: October 2012
History of Changes
  Purpose

For HIV-infected patients who have access to treatment, liver diseases are a major cause of morbidity and mortality. Hepatitis C is the most frequently encountered liver condition in this population. Both diseases allow a higher level of poisonous substances (toxins) normally produced by the bacteria present in the gut to enter the bloodstream. This leads to a chronic inflammatory state, which results in faster development of liver scars (fibrosis) and ultimately, end stage disease (cirrhosis). To prevent this from happening, the use of antibiotics has been attempted to reduce the quantity of gut flora in the hopes of lowering the amount of toxins produced. These trials have shown promising results, but the antibiotics studied had major side effects and were not designed for continuous use. Rifaximin is a non absorbable antibiotic with very few side effects. It is already used for long periods of time in cirrhotic patients to treat the effects of cirrhosis on the brain (encephalopathy). This project will try to determine if rifaximin, by reducing the level of toxins produced by the bacteria in the gut, can improve the evolution of liver fibrosis in HIV-infected patients with hepatitis C. In this pilot study, ten patients will be followed for one year. They will be included if they are starting on rifaximin, for its currently approved FDA indication (hepatic encephalopathy).


Condition Intervention Phase
HIV
Hepatitis C
 Drug: Rifaximin
 Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Impact of Rifaximin on Liver Fibrosis in HIV-Infected Patients With Liver Disease

Resource links provided by NLM:

Drug Information available for: Rifaximin
U.S. FDA Resources

Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Liver fibrosis progression as measured by transient elastography [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.

  • Liver fibrosis progression as measured by transient elastography [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.

  • Liver fibrosis progression as measured by transient elastography [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.

  • Liver fibrosis progression as measured by transient elastography [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.

  • Liver fibrosis progression as measured by transient elastography [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.


Secondary Outcome Measures:
  • Levels of sCD14 in HIV-infected patients with liver disease taking rifaximin [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    sCD14 is a surrogate marker of bacterial translocation

  • Levels of sCD14 in HIV-infected patients with liver disease taking rifaximin [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    sCD14 is a surrogate marker of bacterial translocation

  • Levels of sCD14 in HIV-infected patients with liver disease taking rifaximin [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    sCD14 is a surrogate marker of bacterial translocation

  • Levels of sCD14 in HIV-infected patients with liver disease taking rifaximin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    sCD14 is a surrogate marker of bacterial translocation

  • Levels of sCD14 in HIV-infected patients with liver disease taking rifaximin [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    sCD14 is a surrogate marker of bacterial translocation

  • Safety of prolonged use of rifaximin in HIV patients taking many other medications [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: October 2012
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rifaximin
All patients will be taking rifaximin 550 mg twice daily
 Drug: Rifaximin
All patients will be taking rifaximin 550 mg twice daily for one year for a diagnosis of hepatic encephalopathy
Other Name: XIFAXAN

Detailed Description:

Many studies have already proved the deleterious effects of LPS on HIV and hepatic diseases evolution. There has never been a concerted effort to prevent the progression of liver disease in these patients. To date, the only treatment is initiation of antiretroviral therapy. Rifaximin could be an easy and well tolerated way to improve the outcome of liver disease in HIV-infected patients. We hypothesize that it could help to slow down the progression of liver disease at any stage in these patients. This is a pilot study. Ten patients placed on rifaximin by their physician for a mild hepatic encephalopathy will be monitored over a period of one year. The evaluation of the fibrosis will be done through transient elastography every 3 months. Bacterial translocation will be evaluated through the dosing of soluble CD14. The safety of the prolonged use of rifaximin in HIV-infected patients will also be assessed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged over 18 years old that can give an informed consent
  • HIV-infected patients with hepatitis C associated liver disease demonstrated by a fibroscan score above 8 kiloPascals
  • Patients placed on rifaximin by their physician for a mild hepatic encephalopathy

Exclusion Criteria:

  • Any patient unable to give informed consent.
  • Patients on hepatitis C treatment
  • Patients allergic to rifaximin or rifamycin
  • Patients on any prolonged antibiotic treatment including patients on tuberculosis treatment.
  • Patients with history of Clostridium difficile infection
  • Uncontrolled HIV infection: CD4 less than 200 or detectable viral load Patients need to be on a stable ART regimen for at least one month.
  • Patient on a HIV regimen including an unboosted protease inhibitor.
  • Acute hepatitis of any cause.
  • Child C cirrhosis
  • Patients on dialysis
  • Pregnant women or childbearing age women not accepting to use an effective contraceptive method Acceptable methods are double barrier methods (condom with spermicide jelly or diaphragm with spermicide), hormonal methods (oral contraceptives, patches or medroxyprogesterone acetate), or an intrauterine device with a documented failure rate of less than 1% per year. Females who have been surgically sterilized (e.g., hysterectomy or bilateral tubal ligation) or who are postmenopausal (total cessation of menses for >1 year) will not be considered "females of childbearing potential."
  • Usual exclusion criteria for FibroScan (pregnancy, BMI over 40, ascites, pacemaker or defibrillator).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01654939

Contacts
Contact: Douglas T Dieterich, MD 212-241-7270 douglas.dieterich@mountsinai.org
Contact: Valerie Martel-Laferriere, MD 212-241-7270 valerie.martel-laferriere@mountsinai.org

Locations
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Principal Investigator: Douglas T Dieterich, MD            
Sponsors and Collaborators
Douglas T. Dieterich
Salix Pharmaceuticals
Investigators
Principal Investigator: Douglas T Dieterich, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Douglas T. Dieterich, Principal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01654939     History of Changes
Other Study ID Numbers: GCO 12-0794, HSM# 12-00436
Study First Received: July 30, 2012
Last Updated: October 24, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
HIV
hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
 Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Rifaximin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on June 13, 2013