HIVNCT02012309
Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses
A study testing PCV-13 and PPSV-23 in people with HIV and Pneumococcal Infections, run by University of Colorado, Denver at 3 sites in United States.
Trial summary
Human Immunodeficiency Virus (HIV) infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/acquired immune deficiency syndrome (AIDS) virus itself. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV, Pneumococcal Infections, Pneumococcal Vaccines
- What is being tested?
- PCV-13 and PPSV-23
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesUnited States
- Study dates
- Aug 2014to Jun 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Colorado-Denver
Aurora, Colorado, 80045
Denver Health and Hospitals
Denver, Colorado, 80204
Denver VA Medical Center
Denver, Colorado, 80220
About this study
Human Immunodeficiency Virus (HIV) infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/acquired immune deficiency syndrome (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.
- Conditions
- HIV, Pneumococcal Infections, Pneumococcal Vaccines
- Being tested
- PCV-13, PPSV-23
- Keywords
- HIV, Streptococcus pneumoniae infection, Streptococcus pneumoniae colonization, Pneumococcal vaccines, Prevnar, Pneumovax, Nasopharyngeal microbiome
- Medical subject headings
- Pneumococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCV-13Biological
Also called Prevnar
PPSV-23Biological
Also called Pneumovax
| Study group | Role | What they receive |
|---|---|---|
| HIV-seronegative | Experimental | HIV-seronegative subjects will receive Prevnar (PCV-13) at week 0. Receives: Biological: PCV-13 |
| HIV-infected | Experimental | 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. Receives: Biological: PCV-13; Biological: PPSV-23 |
What is being measured
The primary outcome is the main question the study is designed to answer.
B and T cell subsets
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
Measured: Weeks -12, 0, 1, 8, 9, 16
Total IgG, IgM and IgA
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)
Measured: Weeks -12, 0, 1, 8, 9, 16
Antibody-secreting cells
Total IgG, IgM and IgA antibody-secreting cells (ASC) enumerated by enzyme-linked immunospot (ELISPOT) on day 0 and day 7
Measured: Weeks 0, 1, 8, 9
AID and BCL-6 production
RNA extraction for activation-induced cytidine deaminase (AID) and B cell lymphoma protein 6 (BCL6) expression and mutation from stimulated B cells
Measured: Weeks -12, 0, 1, 8, 9, 16
Secondary outcomes (2)
S.pneumoniae colonization and nasopharyngeal microbiome
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
Measured: Weeks -12, 0, 8, 16
S.pneumoniae urine antigen positivity
- pneumoniae urine antigen positivity in relation to colonization
Measured: Week -12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study startAug 2014
- Primary completionJun 2021 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edward N Janoff, MD, Principal investigator, University of Colorado-Denver, Denver VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012309
- Sponsor's protocol ID
- 13-2405
- Other IDs
- R01AI108479
- Status last verified
- Nov 2020
- First submitted
- 10 Dec 2013
- Last updated
- 18 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses
- ClinicalTrials.gov ID
- NCT02012309
- Acronym / sponsor ID
- 13-2405
- Conditions
- HIV, Pneumococcal Infections, Pneumococcal Vaccines
- Keywords
- HIV, Streptococcus pneumoniae infection, Streptococcus pneumoniae colonization, Pneumococcal vaccines, Prevnar, Pneumovax, Nasopharyngeal microbiome
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Aug 2014 (actual)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Human Immunodeficiency Virus (HIV) infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/acquired immune deficiency syndrome (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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV-seronegative | Experimental | Biological: PCV-13HIV-seronegative subjects will receive Prevnar (PCV-13) at week 0. |
| HIV-infected | Experimental | Biological: PCV-13, Biological: PPSV-23HIV-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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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)
- adults aged 18-55 years
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PCV-13Also: Prevnar | Biological | HIV-infected, HIV-seronegative |
| PPSV-23Also: Pneumovax | Biological | HIV-infected |
Primary outcome
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
2 secondary outcomes
S.pneumoniae colonization and nasopharyngeal microbiome
Time frame: Weeks -12, 0, 8, 16
S.pneumoniae urine antigen positivity
Time frame: Week -12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward N Janoff, MD principal investigator
University of Colorado-Denver, Denver VA Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PCV-13 and PPSV-23 in people with HIV and Pneumococcal Infections, run by University of Colorado, Denver at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
B and T cell subsets (time frame: Weeks -12, 0, 1, 8, 9, 16). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2020.