Open Label Study to Evaluate the Safety, Efficacy, Viral Kinetics, Genetic, Epigenetic, and Proteomic Expression of Weekly Peginterferon Alpha 2a and Ribavirin Therapy for Chronic Hepatitis C in Latino Subjects With and Without HIV Co-infection

This study has been terminated.
Sponsor:
Collaborator:
Fundacion de Investigacion de Diego
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT01182298
First received: August 13, 2010
Last updated: January 14, 2014
Last verified: March 2013
  Purpose

Background:

  • Peginterferon alfa-2a has been approved by the U.S. Food and Drug Administration (FDA) to treat adults with chronic hepatitis C virus (HCV) infection with liver disease who have not been previously treated with interferon-alpha drugs (which improve immune system response to infection). Ribavirin has been approved by the FDA and is usually given in combination with interferon drugs such as peginterferon alfa-2a for treatment of chronic HCV.
  • Recent research shows that Latino whites do not respond as well to treatment with peginterferon alfa-2a and ribavirin as non-Latino whites. Various factors such as excessive weight, gender, and insulin resistance were evaluated to explain this difference, but research suggests that underlying factors related to Latino or non-Latino background, possibly genetic and immune differences, may be affecting the response to HCV infection and treatment. However, more research is needed on the effectiveness of peginterferon and ribavirin in Latino subjects with HCV, and with combined and human immunodeficiency virus (HIV) co-infection.

Objectives:

- To evaluate the safety, effectiveness, and viral response of peginterferon alfa-2a and ribavirin therapy for chronic hepatitis C in Latino participants with and without HIV co-infection.

Eligibility:

  • Latino individuals at least 18 years of age who have been diagnosed with hepatitis C. (Both parents and all grandparents of the participant must be Latino, with Spanish as the primary language. Participants must be white; native aboriginal Indians, Asians, and blacks will be excluded.)
  • Individuals who are co-infected with the human immunodeficiency virus (HIV) are also eligible for the study.

Design:

  • Participants will be screened with a complete medical history, blood and urine samples, imaging studies (e.g., abdominal ultrasound, chest x-ray) and an eye exam. Participants who have not had a liver biopsy within the past year will have one as part of the screening for the study.
  • Participants will receive ribavirin twice a day and an injection of peginterferon alfa-2a once a week. Participants or someone close to them will be shown how to give the injections.
  • Participants will have regular blood and urine tests to evaluate HIV and HCV viral loads and interferon levels.
  • At week 16, participants whose viral loads have not responded to therapy will stop treatment. At week 24, participants who still have detectable virus levels will stop treatment. Participants who show improvement will end treatment at week 48. All participants will have blood tests and imaging studies at the end of their treatment.
  • Participants will have a follow-up visit 6 months after the end of treatment for final blood tests and imaging studies.

Condition Intervention Phase
Hepatitis C
HIV
Drug: Pegylated interferon with ribavirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study to Evaluate the Genetic, Epigenetic, and Proteomic Expression in Latino Participants With and Without HIV Coinfection Receiving Treatment for Hepatitis C

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary end point of this study is the log change in HCV RNA levels on Day 7 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety, efficacy, viral kinetics, immunological responses, genetic, epigenetic, and proteomic expression of weekly peginterferon alpha-2a and daily ribavirin therapy for chronic hepatitis C in Latino subjects with and without HIV co-infection. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: July 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pegylated interferon with ribavirin
    N/A
Detailed Description:

Hepatitis C is a major health problem affecting 100- 300 million individuals worldwide. Chronic hepatitis C virus (HCV) infection leads to cirrhosis in approximately 20% of subjects over a period of 1-20 years. Hepatitis C is now the most common indication for liver transplantation in the United States. infection occurs in one-third of all HIV-infected individuals, and the natural history among HIV-1 infected individuals demonstrates higher levels of HCV viremia, faster rates of progression and cirrhosis. There have been very few studies addressing the lower therapeutic response rates in minorities outside of African Americans. A recent study showed that Latino white subjects respond less effectively (34%) than non Latino white subjects (49%) given the same treatment even after adjusting for various important factors. As the current landscape for treatment of HCV changes, it would be important to evaluate factors responsible for therapeutic response in Latino patients.

This is a study to address the genetic, epigenetic, and proteomic expression during therapy for chronic hepatitis C in Latino participants with and without HIV co-infection. One hundred Latino participants who have evidence of chronic hepatitis C with and without HIV who are receiving treatment for HCV will be enrolled. The results of this study will enable us to explore reasons for the differential therapeutic response rates with Hepatitis C treatment in Latino participants with and without HIV coinfection.

  Eligibility

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

A subject must satisfy all of the following criteria to be eligible to participate in this study:

  1. Latino ethnicity. Latino ethnic background will be defined as a geographic, historical, and cultural heritage shared among persons from Spanish-speaking countries in South and Central America, Mexico, and the Caribbean. Both parents and all grandparents of the participant have to be Latino, with Spanish as the primary language. Participants have to be white; native aboriginal Indians, Asians, and blacks will be excluded.
  2. Age greater than or equal to 18 years.
  3. Documentation of hepatitis C infection by demonstration of a positive test for hepatitis C antibody and HCV RNA level of greater than or equal to 2,000 IU/mL.
  4. Documentation of HIV-1 infection in the second group of co-infected participants by a licensed enzyme-linked immunosorbent assay and confirmed by a Western blot or by HIV polymerase chain reaction positive.
  5. Participants with HIV: CD4+ cell counts greater than or equal to 100 cells/mm(3) or CD4+ cell percentage greater than or equal to 14%.
  6. Ability to provide informed consent and willingness to comply with the study requirements, storage of blood samples and clinic policies.
  7. Participants must have a primary care physician managing medical problems.
  8. For HIV infected participants, care provided by a primary physician must be consistent with the current DHHS guidelines. For those on therapy, HAART will be provided by their physician.
  9. Willing to undergo genetic testing
  10. About to start HCV treatment (with or without direct acting agents DAAs)

EXCLUSION CRITERIA:

A subject will be ineligible to participate in this study if any of the following criteria are met:

  1. Unable to comply with research study visits
  2. Have any condition that the investigator considers a contraindication to study participation.
  3. Pregnant or breastfeeding women.
  4. Patients with poor venous access
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01182298

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Fundacion de Investigacion de Diego
Investigators
Principal Investigator: Shyamasundaran Kottilil, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT01182298     History of Changes
Other Study ID Numbers: 100159, 10-I-0159
Study First Received: August 13, 2010
Last Updated: January 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Latino
HCV
pegIFN
Viral Kinetics
IL-28 Haplotype

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Coinfection
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Infection
Parasitic Diseases
Hepatitis, Chronic
Interferons
Ribavirin
Peginterferon alfa-2a
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014