HIV-1-infectionNCT03416790
IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment
An observational study of HIV-1-infection, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 12 sites in 2 countries.
Trial summary
IMPAACT 2015 is a cross-sectional, exploratory study that will investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. Read more about this study
- Who is it for?
- Ages 13 to 24 years
- Conditions the study is for
- HIV-1-infection
- How many people
- 24 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 6 Feb 2019to 26 Mar 2020
- Phase
- Observational
- 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 13 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Perinatally HIV-1-infected youth and young adults (13-24 years of age) with cognitive impairment, on suppressive antiretroviral therapy, from study sites in the United States
Who may be able to join
- 13-24 years of age (inclusive) at enrollment (i.e., on the day the participant is enrolled in the study)
- Spoken fluency in English or Spanish
- If not of legal age to provide independent informed consent: Parent or legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation
- If of legal age but not able to provide independent informed consent due to cognitive impairment as determined by site standard operating procedures (SOPs) and consistent with site institutional review board/ethics committee (IRB/EC) policies and procedures: Parent, legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation
- If of legal age and able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: Willing and able to provide written informed consent for study participation
- Has confirmed perinatal HIV-1 infection - with no documented evidence to suggest another route of transmission - based on review of available medical records
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- Has been taking combination ART comprised of at least three agents from at least two classes of antiretroviral therapy for at least 12 consecutive months prior to enrollment as determined by the site investigator or designee based on participant or parent/guardian report and available medical records; regimen changes within the 12 months prior to enrollment are permitted, provided the virologic requirements in criterion below are met
- Has at least two consecutive documented plasma HIV-1 RNA values less than 40 copies/mL, at least three months apart, in the 12 months prior to enrollment; one of these values must be based on testing of a specimen collected within the 60 days prior to enrollment
- Has a Fluid Cognition Composite Score at least one-and-a-half standard deviations below the published normative mean (i.e., less than 78) based on administration of the NIH Toolbox Cognition Battery
Who cannot join
- Any ART interruption for more than seven consecutive days in the 12 months prior to enrollment
- Any HIV-1 RNA value greater than 200 copies/mL in the 12 months prior to enrollment
- Completed any of the NIH Toolbox subtests specified within 90 days prior to screening
- Any documented full scale intelligence quotient (IQ) score more than three standard deviations below the published normative mean (i.e., less than 55) or a Fluid Cognition Composite Score more than three standard deviations below the published normative mean (i.e., less than 55) based on administration of the NIH Toolbox Cognition Battery at screening
- Any documented diagnosis of autism spectrum disorder, schizophrenia, or other psychotic disorder
- Any known prior infection of the CNS that may be persistent or recurrent (e.g., cryptococcal meningitis, neurosyphilis)
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- Any known non-HIV-related cause or significant contributing factor for cognitive impairment (e.g., birth injury, head injury, stroke, major or mild neurocognitive disorder due to a condition other than HIV) per Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-V) criteria
- Any known or suspected current contraindication to lumbar puncture
- Any current sensory or motor impairment severe enough to preclude participation in study evaluations (e.g., blindness, lack of upper limb control)
- If female and of reproductive potential (defined as having experienced menarche and having no documented history of a sterilization procedure), known or suspected pregnancy
- Any serious or otherwise clinically significant infection of the CNS or bloodstream (other than HIV-1 infection) within 30 days prior to enrollment
- Any live vaccine received within 30 days prior to enrollment
- Any other (non-live) vaccine received within 7 days prior to enrollment
- Received prolonged (more than 14 days) or high dose immunosuppressants within 30 days prior to enrollment (high dose would include >1 mg/kg prednisone (or equivalent) or any biologic immunosuppressant such as monoclonal antibody based therapy)
- Ever received any medication or other approved or investigational agent that may impact HIV-1 reservoirs, including but not limited to: HIV-1 vaccines, HIV-1 gene therapies, Anti-HIV-1 broadly neutralizing antibodies (e.g., VRC01), Anti-PD-1 or anti-PD-L1 antibody, Histone deacetylase inhibitors (e.g., vorinostat, romidepsin, panobinostat), Toll-like receptor agonists, Cytotoxic chemotherapies, Roxolitinib, and Sirolimus
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States11 sites
Emory University School of Medicine (CRS 5030)
Atlanta, Georgia, 30322
University of Colorado, Denver (CRS 5052)
Aurora, Colorado, 80045
Johns Hopkins University (CRS 5092)
Baltimore, Maryland, 21287
Boston Medical Center Pediatric HIV Program (CRS 5011)
Boston, Massachusetts, 02118
University of Southern California (CRS 5048)
Los Angeles, California, 90089
David Geffen School of Medicine at University of California, Los Angeles (CRS 5112)
Los Angeles, California, 90095
St. Jude Children's Research Hospital (CRS 6501)
Memphis, Tennessee, 38105
University of California, San Diego Mother-Child-Adolescent HIV Program (CRS 4601)
San Diego, California, 92103
Seattle Children's Hospital (CRS 5017)
Seattle, Washington, 98105
Bronx-Lebanon Hospital Center (CRS 5114)
The Bronx, New York, 10457
Jacobi Medical Center (CRS 5013)
The Bronx, New York, 10461
Puerto Rico1 site
University of Puerto Rico Pediatric HIV/AIDS Research Program (CRS 6601)
San Juan, 00936
About this study
IMPAACT 2015 is a cross-sectional, exploratory study that will investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. Findings from this study will advance understanding of the role of the CNS in HIV-1 persistence and its implications for future HIV-1 remission research.
Read the detailed description
IMPAACT 2015 is a cross-sectional, exploratory study aiming to investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. CSF will be examined for persistence of HIV-1 RNA or DNA despite antiretroviral therapy (ART) and for evidence of intrathecal inflammation. Perinatally-infected youth and young adults are of particular interest because there are very limited CSF data available in this population and reasons to be concerned about the CNS reservoir. In addition, measures of HIV-1 RNA in the CSF and associated biomarkers have not previously been explored in this population. A better understanding of viral persistence in the CSF, as well as CSF biomarker profiles, will provide preliminary data to move the field forward in understanding the role of the CNS in HIV-1 persistence and will have implications for future HIV-1 remission research.
- Conditions
- HIV-1-infection
- Keywords
- Central Nervous System, HIV Persistence, HIV Reservoirs
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of quantifiable cell-free HIV-1 RNA CSF
Quantifiable cell-free HIV-1 RNA CSF defined as an HIV-1 RNA assay result of ≥20 copies/mL
Measured: Within 30 Days of Screening Initiation
Prevalence of detectable HIV-1 DNA in CSF cell pellets
Detectable HIV-1 DNA in CSF cell pellets defined as an HIV-1 DNA assay result of ≥1 copy in the cell pellet obtained from ≥10 ml of CSF
Measured: Within 30 Days of Screening Initiation
Secondary outcomes (3)
Concentrations of inflammatory and neuronal injury biomarkers in CSF
Biomarkers to be evaluated include neopterin, neurofilament light chain (NFL), tyrosine (Y), lysine (K) and leucine (L) - 40kDa (YKL-40), interleukin (IL-6), C-reactive protein (CRP), interferon gamma-induced protein 10 (IP-10/CXCL10), monocyte chemoattractant protein 1 (MCP-1/CCL2), tumor necrosis factor (TNF-α), sCD14, soluble CD163 (sCD163), soluble intercellular adhesion molecule type 5 (sICAM-5) (immunoassays). Concentrations of each of these biomarkers in CSF will be summarized descriptively.
Measured: Within 30 Days of Screening Initiation
Concentrations of inflammatory and neuronal injury biomarkers in plasma
Biomarkers to be evaluated include neopterin, neurofilament light chain (NFL), tyrosine (Y), lysine (K) and leucine (L) - 40kDa (YKL-40), interleukin (IL-6), C-reactive protein (CRP), interferon gamma-induced protein 10 (IP-10/CXCL10), monocyte chemoattractant protein 1 (MCP-1/CCL2), tumor necrosis factor (TNF-α), sCD14, soluble CD163 (sCD163), soluble intercellular adhesion molecule type 5 (sICAM-5) (immunoassays). Concentrations of each of these biomarkers in plasma will be summarized descriptively.
Measured: Within 30 Days of Screening Initiation
Associations of the above-listed secondary outcomes with the primary outcomes
Associations will be assessed with Spearman correlations (and corresponding confidence intervals).
Measured: Within 30 Days of Screening Initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2018
- Study start6 Feb 2019
- Primary completion26 Mar 2020
- Study completion26 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Maternal Pediatric Adolescent AIDS Clinical Trials Group
- Sponsor type
- Research network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Ann Chahroudi, MD, PhD, Study chair, Emory UniversityThor Wagner, MD, Study chair, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03416790
- Sponsor's protocol ID
- IMPAACT 2015
- Other IDs
- DAIDS ID 35123
- Status last verified
- Jul 2020
- First submitted
- 18 Jan 2018
- Last updated
- 8 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment
- ClinicalTrials.gov ID
- NCT03416790
- Acronym / sponsor ID
- IMPAACT 2015
- Conditions
- HIV-1-infection
- Keywords
- Central Nervous System, HIV Persistence, HIV Reservoirs
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- International Maternal Pediatric Adolescent AIDS Clinical Trials GroupResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
- Study start
- 6 Feb 2019 (actual)
- Primary completion
- 26 Mar 2020 (actual)
- Study completion
- 26 Mar 2020 (actual)
- First posted
- 31 Jan 2018 (actual)
- 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.
IMPAACT 2015 is a cross-sectional, exploratory study that will investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. Findings from this study will advance understanding of the role of the CNS in HIV-1 persistence and its implications for future HIV-1 remission research.
Detailed description
IMPAACT 2015 is a cross-sectional, exploratory study aiming to investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. CSF will be examined for persistence of HIV-1 RNA or DNA despite antiretroviral therapy (ART) and for evidence of intrathecal inflammation. Perinatally-infected youth and young adults are of particular interest because there are very limited CSF data available in this population and reasons to be concerned about the CNS reservoir. In addition, measures of HIV-1 RNA in the CSF and associated biomarkers have not previously been explored in this population. A better understanding of viral persistence in the CSF, as well as CSF biomarker profiles, will provide preliminary data to move the field forward in understanding the role of the CNS in HIV-1 persistence and will have implications for future HIV-1 remission research.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 13 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Perinatally HIV-1-infected youth and young adults (13-24 years of age) with cognitive impairment, on suppressive antiretroviral therapy, from study sites in the United States
Key inclusion criteria (9 listed)
- 13-24 years of age (inclusive) at enrollment (i.e., on the day the participant is enrolled in the study)
- Spoken fluency in English or Spanish
- If not of legal age to provide independent informed consent: Parent or legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation
- If of legal age but not able to provide independent informed consent due to cognitive impairment as determined by site standard operating procedures (SOPs) and consistent with site institutional review board/ethics committee (IRB/EC) policies and procedures: Parent, legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation
- If of legal age and able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: Willing and able to provide written informed consent for study participation
Key exclusion criteria (15 listed)
- Any ART interruption for more than seven consecutive days in the 12 months prior to enrollment
- Any HIV-1 RNA value greater than 200 copies/mL in the 12 months prior to enrollment
- Completed any of the NIH Toolbox subtests specified within 90 days prior to screening
- Any documented full scale intelligence quotient (IQ) score more than three standard deviations below the published normative mean (i.e., less than 55) or a Fluid Cognition Composite Score more than three standard deviations below the published normative mean (i.e., less than 55) based on administration of the NIH Toolbox Cognition Battery at screening
- Any documented diagnosis of autism spectrum disorder, schizophrenia, or other psychotic disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of quantifiable cell-free HIV-1 RNA CSF
Time frame: Within 30 Days of Screening Initiation
Quantifiable cell-free HIV-1 RNA CSF defined as an HIV-1 RNA assay result of ≥20 copies/mL
Prevalence of detectable HIV-1 DNA in CSF cell pellets
Time frame: Within 30 Days of Screening Initiation
Detectable HIV-1 DNA in CSF cell pellets defined as an HIV-1 DNA assay result of ≥1 copy in the cell pellet obtained from ≥10 ml of CSF
3 secondary outcomes
Concentrations of inflammatory and neuronal injury biomarkers in CSF
Time frame: Within 30 Days of Screening Initiation
Concentrations of inflammatory and neuronal injury biomarkers in plasma
Time frame: Within 30 Days of Screening Initiation
Associations of the above-listed secondary outcomes with the primary outcomes
Time frame: Within 30 Days of Screening Initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 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.
Ann Chahroudi, MD, PhD study chair
Emory University
Thor Wagner, MD study chair
University of Washington
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 12 sites in 2 countries.
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 9 inclusion and 15 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: finished, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Puerto Rico. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Prevalence of quantifiable cell-free HIV-1 RNA CSF (time frame: Within 30 Days of Screening Initiation). The study lists 2 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 8 Jul 2020.