- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03416790
IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment
July 7, 2020 updated by: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
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.
Study Overview
Status
Completed
Conditions
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 Type
Observational
Enrollment (Actual)
24
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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San Juan, Puerto Rico, 00936
- University of Puerto Rico Pediatric HIV/AIDS Research Program (CRS 6601)
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California
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Los Angeles, California, United States, 90089
- University of Southern California (CRS 5048)
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Los Angeles, California, United States, 90095
- David Geffen School of Medicine at University of California, Los Angeles (CRS 5112)
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San Diego, California, United States, 92103
- University of California, San Diego Mother-Child-Adolescent HIV Program (CRS 4601)
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado, Denver (CRS 5052)
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University School of Medicine (CRS 5030)
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University (CRS 5092)
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Massachusetts
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Boston, Massachusetts, United States, 02118
- Boston Medical Center Pediatric HIV Program (CRS 5011)
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New York
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Bronx, New York, United States, 10457
- Bronx-Lebanon Hospital Center (CRS 5114)
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Bronx, New York, United States, 10461
- Jacobi Medical Center (CRS 5013)
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Tennessee
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Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital (CRS 6501)
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Washington
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Seattle, Washington, United States, 98105
- Seattle Children's Hospital (CRS 5017)
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
13 years to 24 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
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
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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)
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Case-Only
- Time Perspectives: Cross-Sectional
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Prevalence of quantifiable cell-free HIV-1 RNA CSF
Time Frame: Within 30 Days of Screening Initiation
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Quantifiable cell-free HIV-1 RNA CSF defined as an HIV-1 RNA assay result of ≥20 copies/mL
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Within 30 Days of Screening Initiation
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Prevalence of detectable HIV-1 DNA in CSF cell pellets
Time Frame: Within 30 Days of Screening Initiation
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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
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Within 30 Days of Screening Initiation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Concentrations of inflammatory and neuronal injury biomarkers in CSF
Time Frame: Within 30 Days of Screening Initiation
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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.
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Within 30 Days of Screening Initiation
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Concentrations of inflammatory and neuronal injury biomarkers in plasma
Time Frame: Within 30 Days of Screening Initiation
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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.
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Within 30 Days of Screening Initiation
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Associations of the above-listed secondary outcomes with the primary outcomes
Time Frame: Within 30 Days of Screening Initiation
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Associations will be assessed with Spearman correlations (and corresponding confidence intervals).
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Within 30 Days of Screening Initiation
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Chair: Ann Chahroudi, MD, PhD, Emory University
- Study Chair: Thor Wagner, MD, University of Washington
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 6, 2019
Primary Completion (Actual)
March 26, 2020
Study Completion (Actual)
March 26, 2020
Study Registration Dates
First Submitted
January 18, 2018
First Submitted That Met QC Criteria
January 24, 2018
First Posted (Actual)
January 31, 2018
Study Record Updates
Last Update Posted (Actual)
July 8, 2020
Last Update Submitted That Met QC Criteria
July 7, 2020
Last Verified
July 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IMPAACT 2015
- DAIDS ID 35123 (Other Identifier: DAIDS CRMS)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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