Trial record 11 of 46 for:    Pneumonia | Open Studies | NIH, U.S. Fed

Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by University of Colorado, Denver
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT02012309
First received: December 10, 2013
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

HIV infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/AIDS virus itself. Treatment of HIV with antiretroviral medications has decreased the frequency of many complications by over 90%, but bacterial pneumonia remains extremely high. Current vaccines are not very effective in preventing these infections in patients with HIV infection. The investigators are studying the cells (B cells) that make antibodies to fight infection by binding to and killing bacteria. The goal is to understand how HIV impairs the ability of B cells to make antibodies in sufficient quantity and of sufficient quality to protect patients with HIV to learn how to enhance protection against these infections. The investigators also seek to understand the role of the bacteria (specifically Streptococcus pneumoniae) that normally live in the nose and throat in the development of pneumonia and other infections.


Condition Intervention
HIV
Pneumococcal Infections
Pneumococcal Vaccines
Biological: PCV-13
Biological: PPSV-23

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • B and T cell subsets [ Time Frame: Weeks -12, 0, 1, 8, 9, 16 ] [ Designated as safety issue: No ]
    Activation and subset distribution of B and T cell subsets and cluster of differentiation positive (CD4+) T cells and T follicular helper (TFH) cells on days 0 and 7 after stimulation

  • Total IgG, IgM and IgA [ Time Frame: Weeks -12, 0, 1, 8, 9, 16 ] [ Designated as safety issue: No ]
    Total immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) produced from culture of peripheral blood mononuclear cells (PBMC) stimulated in triplicate with B cell stimuli on day 7 by enzyme-linked immunosorbent assay (ELISA)

  • Antibody-secreting cells [ Time Frame: Weeks 0, 1, 8, 9 ] [ Designated as safety issue: No ]
    Total IgG, IgM and IgA antibody-secreting cells (ASC) enumerated by enzyme-linked immunospot (ELISPOT) on day 0 and day 7

  • AID and BCL-6 production [ Time Frame: Weeks -12, 0, 1, 8, 9, 16 ] [ Designated as safety issue: No ]
    RNA extraction for activation-induced cytidine deaminase (AID) and B cell lymphoma protein 6 (BCL6) expression and mutation from stimulated B cells


Secondary Outcome Measures:
  • S.pneumoniae colonization and nasopharyngeal microbiome [ Time Frame: Weeks -12, 0, 8, 16 ] [ Designated as safety issue: No ]
    Prevalence of nasopharyngeal S. pneumoniae determined by quantitative polymerase chain reaction(Q-PCR) and 16S ribosomal RNA (rRNA) sequencing, related microbiota (commensal bacteria) and correlation between colonization and levels of pneumococcal capsule-specific IgG

  • S.pneumoniae urine antigen positivity [ Time Frame: Week -12 ] [ Designated as safety issue: No ]
    S. pneumoniae urine antigen positivity in relation to colonization


Estimated Enrollment: 120
Study Start Date: January 2014
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HIV-seronegative
HIV-seronegative subjects will receive Prevnar (PCV-13) at week 0.
Biological: PCV-13
Other Name: Prevnar
Experimental: HIV-infected
HIV-infected subjects will receive Prevnar (PCV-13) at week 0, and Pneumovax (PPSV-23) at week 8 per Advisory Committee on Immunization Practices (ACIP) guidelines.
Biological: PCV-13
Other Name: Prevnar
Biological: PPSV-23
Other Name: Pneumovax

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For HIV-infected subjects:

  • adults aged 18-55 years
  • >200 CD4+ T-cells/microliter
  • no antiretroviral therapy (at the time of nasal swab/week 0)
  • receiving antiretroviral therapy for >6 weeks (at the time of vaccination/week 12)

For HIV-seronegative controls:

  • adults aged 18-55 years

Exclusion Criteria:

For all subjects:

  • age <18 or >55 years
  • history of prior pneumococcal vaccination
  • immunosuppressive therapy, defined as: prednisone >15mg/day currently or >14 days in the past 3 months, cytotoxic agents, anti-metabolites, cyclosporine, anti-tumor necrosis factor, B cell monoclonal antibodies
  • current or chronic pulmonary infection (bacterial, fungal, mycobacterial), pneumonia, or rhinosinusitis within 2 months
  • chronic lung disease
  • renal insufficiency, defined as serum creatinine >1.6
  • active liver disease, including hepatitis C virus infection
  • history of splenectomy
  • history of antibacterial therapy within 3 months of nasal swab (week 0)
  • current alcohol abuse
  • chronic heart disease
  • diabetes
  • current cigarette smoking
  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: NCT02012309

Contacts
Contact: Lindsay K Nicholson, MD 303-399-8020 ext 3557 lindsay.nicholson@ucdenver.edu
Contact: Edward N Janoff, MD 303-399-8020 ext 3258 edward.janoff@ucdenver.edu

Locations
United States, Colorado
University of Colorado-Denver Not yet recruiting
Aurora, Colorado, United States, 80045
Denver VA Medical Center Not yet recruiting
Denver, Colorado, United States, 80220
Denver Health and Hospitals Not yet recruiting
Denver, Colorado, United States, 80204
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Edward N Janoff, MD University of Colorado-Denver, Denver VA Medical Center
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02012309     History of Changes
Other Study ID Numbers: 13-2405, R01AI108479
Study First Received: December 10, 2013
Last Updated: January 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
HIV
Streptococcus pneumoniae infection
Streptococcus pneumoniae colonization
Pneumococcal vaccines
Prevnar
Pneumovax
Nasopharyngeal microbiome

Additional relevant MeSH terms:
Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 24, 2014