Immunologic Memory (Supp. of ATN 024)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00142753
First received: August 31, 2005
Last updated: October 8, 2013
Last verified: August 2013
  Purpose

This is an exploratory, laboratory-based evaluation of cellular immune response to immunization with hepatitis B surface antigen in HIV-infected and HIV-uninfected adolescents. This is a substudy of ATN 024 and ATN 025. This substudy will compare cellular immune response in responders and nonresponders to immunization and also evaluate the relationship of these factors to the persistence of known correlates of serologic protection for the hepatitis B virus.


Condition Intervention Phase
HIV Infections
Biological: Engerix B
Biological: Twinrix for ATN 024
Biological: Recombivax
Biological: Twinrix for ATN 025
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Correlates of HBV-Specific B Cell Memory Following Vaccination in HIV-Infected Adolescents and HIV-Uninfected Adolescents: A Substudy of ATN 024 and ATN 025

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • To measure interferon-γ (IFN-γ), interleukin -4 (IL-4), and interleukin-10 (IL-10) production in serologic responders and non-responders. [ Time Frame: Before and one month after receipt of primary series of immunization. ] [ Designated as safety issue: No ]
  • To measure concentration of hepatitis B antibodies in serologic responders and non-responders. [ Time Frame: 1, 2, and 4 weeks after supplemental vaccine dose. ] [ Designated as safety issue: No ]
  • To measure concentration of antibody-secreting cells in serologic responders and non-responders. [ Time Frame: Before and one month after receipt of primary series of immunization. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measure whether the profile of cytokine secretion or the number of antibody-secreting cells can be used as a predictor of anamnestic response to a supplemental vaccine dose following serologic nonresponse to a primary series of immunization. [ Time Frame: Prior to immunization, 1 month after primary immunization, at study exit (week 72 for ATN 024; week 76 for ATN 025); at 2 & 4 weeks after supplemental immunization in nonresponders, & at study exit for ATN 024 subjects. ] [ Designated as safety issue: No ]
  • To compare the rate of loss of antibody-secreting cells after vaccination through the end of the study in each vaccine arm. [ Time Frame: Prior to immunization, 1 month after completion of primary immunization and at study exit. ] [ Designated as safety issue: No ]

Enrollment: 95
Study Start Date: August 2005
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A1: ATN 024 Energix-B Standard Adult Dose Biological: Engerix B
Standard adult dose for A1; increased adult dose for A2. Doses at Entry, Weeks 4 and 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive Engerix-B increased adult dose at Week 48.
Other Name: There are no other names.
Experimental: A2: ATN 024 Engerix-B Increased Adult Dose Biological: Engerix B
Standard adult dose for A1; increased adult dose for A2. Doses at Entry, Weeks 4 and 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive Engerix-B increased adult dose at Week 48.
Other Name: There are no other names.
Active Comparator: A3: ATN 024 Twinrix Standard Adult Dose Biological: Twinrix for ATN 024
Standard adult dosage, taken at Entry, Weeks 4 and 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive Engerix-B increased adult dose at week 48.
Other Name: There are no other names.
Experimental: B1: ATN 025 Recombivax Biological: Recombivax
Dosage at entry and week 24; non-responders ((<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive 3rd dose of Recombivax during weeks 48-72.
Other Name: There are no other names.
Experimental: B2: ATN 025 Twinrix Biological: Twinrix for ATN 025
Doses at Entry and Week 24. Non-responders (<10 IU/mL of antibody at week 28/4 weeks after dose #3) will receive a dose of Recombivax during week 48-72.
Other Name: There are no other names.

Detailed Description:

This substudy will enroll volunteers from participants of ATN 024 and ATN 025. Participants in ATN 024 are HIV-infected youths aged 12-24 years while participants in ATN 025 are HIV-uninfected youths aged 12-17 years. These youths must also be negative for HBV core antibody, HBV surface antigen, and HBV surface antibody to be eligible.

Blood will be drawn from study participants prior to immunization, 1 month after completion of primary immunization and at study exit (week 72 for ATN 024 and week 76 for ATN 025) for cytokine assays and enumeration of antibody-secreting cells. In addition, the antibody to HBV surface antigen will be determined 2 and 4 weeks after supplemental immunization in nonresponders to the primary series and at study exit.

This laboratory substudy is designed to evaluate some aspects of cellular immune response to hepatitis B vaccination that are directly related to the generation and durability of antibody response to HBV surface antigen in HIV-infected and HIV-uninfected adolescents. Cytokine production by peripheral mononuclear cells will be determined following in-vitro stimulation, and antibody-secreting cells will be enumerated.

  Eligibility

Ages Eligible for Study:   12 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects that are eligible for participation in ATN 024 and ATN 025 are eligible for ATN 048. Subjects consented for ATN 024 or ATN 025 should be consented for ATN 048 at the same time. A written informed assent/consent must be obtained from the subject along with written parental/legal guardian permission as determined by the local IRB before any study-related procedures are performed.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00142753

Locations
United States, California
Childrens Hosp of Los Angeles
Los Angeles, California, United States, 90027
University of California at San Francisco
San Franciso, California, United States, 94118
United States, District of Columbia
Children's Hosp Natinal Med Center
Washington, District of Columbia, United States, 20010
United States, Louisiana
Tulane Med Center
New Orleans, Louisiana, United States, 70112
Sponsors and Collaborators
Investigators
Study Chair: Stephen Obaro, MBBS, PhD ATN
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00142753     History of Changes
Other Study ID Numbers: ATN 048
Study First Received: August 31, 2005
Last Updated: October 8, 2013
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Hepatitis B vaccines
HIV-infected adolescents
Hepatitis B infection

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on April 20, 2014