Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified August 2017 by University of Colorado, Denver

Sponsor
University of Colorado, Denver

Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party)
University of Colorado, Denver
ClinicalTrials.gov Identifier
NCT02012309

First received: December 10, 2013
Last updated: August 29, 2017
Last Verified: August 2017
History of Changes
Purpose

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses

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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    S. pneumoniae urine antigen positivity in relation to colonization

Estimated Enrollment: 120
Study Start Date: August 2014
Estimated Study Completion Date: March 2018
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

Eligibility

Ages Eligible for Study: 18 Years to 55 Years  
Sexes Eligible for Study: All  
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

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 Recruiting
Aurora, Colorado, United States, 80045
Denver Health and Hospitals Recruiting
Denver, Colorado, United States, 80204
Denver VA Medical Center Recruiting
Denver, Colorado, United States, 80220

Sponsors and Collaborators

University of Colorado, Denver
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator: Edward N Janoff, MD University of Colorado-Denver, Denver VA Medical Center
More Information

More Information


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: August 29, 2017  

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
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine

ClinicalTrials.gov processed this data on December 15, 2017
This information is provided by ClinicalTrials.gov.