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IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment

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ClinicalTrials.gov Identifier: NCT03416790
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : October 16, 2018
Sponsor:
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)
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Brief 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. 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.

Condition or disease
HIV-1-infection

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
Estimated Enrollment : 45 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
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
Actual Study Start Date : September 26, 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. Concentrations of inflammatory and neuronal injury biomarkers in CSF [ Time Frame: Within 30 Days of Screening Initiation ]
    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.

  2. Concentrations of inflammatory and neuronal injury biomarkers in plasma [ Time Frame: Within 30 Days of Screening Initiation ]
    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.

  3. Associations of the above-listed secondary outcomes with the primary outcomes [ Time Frame: Within 30 Days of Screening Initiation ]
    Associations will be assessed with Spearman correlations (and corresponding confidence intervals).


Biospecimen Retention:   Samples With DNA
CSF, PBMC, plasma


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Ages Eligible for Study:   13 Years to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03416790


Contacts
Contact: Anne S Coletti, MS 919-544-7040 ext 11238 acoletti@fhi360.org
Contact: Nicole Montanez, MSW 919-544-7040 nmontanez@fhi360.org

Locations
United States, California
University of Southern California (CRS 5048) Not yet recruiting
Los Angeles, California, United States, 90089
Contact: Allison Bearden, MD, MPH    213-509-9811    allison.bearden@usc.edu   
Contact: Yvonne Morales, LVN    323-865-1561    ytr@usc.edu   
David Geffen School of Medicine at University of California, Los Angeles (CRS 5112) Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Jaime Deville, MD    310-825-9660    jdeville@mednet.ucla.edu   
Contact: Michele Carter, RN    310-206-2165    mfcarter@mednet.ucla.edu   
University of California, San Diego Mother-Child-Adolescent HIV Program (CRS 4601) Not yet recruiting
San Diego, California, United States, 92103
Contact: Stephen Spector, MD    858-534-7055    saspector@ucsd.edu   
Contact: Megan Loughran, BA    858-534-9218    meloughran@ucsd.edu   
United States, Colorado
University of Colorado, Denver (CRS 5052) Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Elizabeth McFarland, MD    303-724-3447    betsy.mcfarland@ucdenver.edu   
Contact: Emily Barr, CPNP, CNM, MSN    720-777-6752    emily.barr@childrenscolorado.org   
United States, Georgia
Emory University School of Medicine (CRS 5030) Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Ann Chahroudi, MD, PhD    404-727-5642    ann.m.chahroudi@emory.edu   
Contact: LaTeshia Seaton, MS, APRN    404-616-5936    lseaton@emory.edu   
United States, Maryland
Johns Hopkins University (CRS 5092) Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Allison Agwu, MD, ScM    410-614-3917    ageorg10@jhmi.edu   
Contact: Aleisha Collinson-Streng, RN, ACRN    443-801-7301    Acolli14@jhmi.edu   
United States, Massachusetts
Boston Medical Center Pediatric HIV Program (CRS 5011) Not yet recruiting
Boston, Massachusetts, United States, 02118
Contact: Ellen Cooper, MD    617-414-5588    ercooper@bu.edu   
Contact: Debra McLaud, RN    617-414-5813    debra.mclaud@bmc.org   
United States, New York
Bronx-Lebanon Hospital Center (CRS 5114) Not yet recruiting
Bronx, New York, United States, 10457
Contact: Murli Purswani, MBChB, FAAP    718-960-1010    mpurswan@bronxleb.org   
Contact: Martha Cavallo, MS, CPNP    718-960-1016    mcacallo@bronxleb.org   
Jacobi Medical Center (CRS 5013) Not yet recruiting
Bronx, New York, United States, 10461
Contact: Andrew Wiznia, MD    718-918-4664    andrew.wiznia@einstein.yu.edu   
Contact: Marlene Burey, MSN, PNP    718-918-4783    marlene.burey@nychhc.org   
United States, Tennessee
St. Jude Children's Research Hospital (CRS 6501) Not yet recruiting
Memphis, Tennessee, United States, 38105
Contact: Patricia Flynn, MD    901-595-4662    pat.flynn@stjude.org   
Contact: Sandra Jones, DNP, CPNP    901-595-5059    sandra.jones2@stjude.org   
United States, Washington
Seattle Children's Hospital (CRS 5017) Recruiting
Seattle, Washington, United States, 98105
Contact: Ann Melvin, MD, MPH    206-987-2535    ann.melvin@seattlechildrens.org   
Contact: Amanda Robson    206-884-1535    amanda.robson@seattlechildrens.org   
Puerto Rico
University of Puerto Rico Pediatric HIV/AIDS Research Program (CRS 6601) Not yet recruiting
San Juan, Puerto Rico, 00936
Contact: Irma Febo, MD    787-759-9595    irma.febo2@upr.edu   
Contact: Ruth Santos, RN, MPH    787-759-9595    ruth.santos@upr.edu   
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
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)
Investigators
Study Chair: Ann Chahroudi, MD, PhD Emory University
Study Chair: Thor Wagner, MD University of Washington

Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT03416790     History of Changes
Other Study ID Numbers: IMPAACT 2015
DAIDS ID 35123 ( Other Identifier: DAIDS CRMS )
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:
Central Nervous System
HIV Persistence
HIV Reservoirs

Additional relevant MeSH terms:
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders