Ignite Creation Date:
2025-12-25 @ 12:56 AM
Ignite Modification Date:
2026-02-26 @ 7:47 PM
Study NCT ID:
NCT00583167
Status:
COMPLETED
Last Update Posted:
2014-05-28
First Post:
2007-12-26
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
CNS (Central Nervous System) Viral Dynamics and Cellular Immunity During AIDS
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015658', 'term': 'HIV Infections'}, {'id': 'D000163', 'term': 'Acquired Immunodeficiency Syndrome'}], 'ancestors': [{'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D012897', 'term': 'Slow Virus Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'whole blood, plasma, CSF'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 4}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2006-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-05', 'completionDateStruct': {'date': '2010-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-05-27', 'studyFirstSubmitDate': '2007-12-26', 'studyFirstSubmitQcDate': '2007-12-28', 'lastUpdatePostDateStruct': {'date': '2014-05-28', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2007-12-31', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2009-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To characterize intrathecal viral replication during chronic untreated HIV-1 infection, and to assess how intrathecal viral replication relates to stage of HIV-1 disease.', 'timeFrame': 'end of study'}, {'measure': 'To measure intrathecal and systemic cellular immune responses against HIV-1 and to assess how these responses relate to intrathecal viral replication.', 'timeFrame': 'end of study'}, {'measure': 'To correlate intrathecal viral replication and anti-HIV CTL responses with the degree of glial activation/proliferation and neuronal dropout in the brain.', 'timeFrame': 'end of study'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['HIV', 'AIDS', 'CNS', 'brain', 'affects'], 'conditions': ['HIV Infections']}, 'descriptionModule': {'briefSummary': 'Understanding whether or not viral replication occurs in the brain during chronic untreated HIV-1 infection is of undeniable importance, and has implications for treatment and research priorities. Evidence suggests that viral replication in the CNS occurs at the extremes of HIV-1 disease. Brain involvement has been reported during acute infection, and there is convincing evidence of CNS viral replication during HIV-associated dementia (HAD) and advanced AIDS. Some human and primate data suggest that viral RNA and proteins may be absent from brains of some individuals with chronic untreated HIV-1 infection despite abundant proviral DNA. However, the extent of viral replication in the brain is not known for most of the 42 million people worldwide living with untreated HIV-1 infection.\n\nWhy is viral replication in the brain such a pivotal issue? Microglial cells and macrophages are primary targets for intrathecal HIV-1 replication, and this can promote neuronal injury through direct effects of gp120 and tat, and indirect induction of toxic mediators. Low-grade injury over years or decades would likely be deleterious, particularly as the population ages. Because treatment guidelines allow systemic HIV-1 replication to continue until CD4+ T cell counts decline considerably, antiretroviral therapy (ART) is not recommended for many persons living with HIV. Demonstrating replication in the brain during chronic HIV-1 infection may affect treatment strategies and encourage investigation.\n\nIdentifying factors that modulate intrathecal viral replication is equally important. Anti-HIV-1 cytotoxic T lymphocytes (CTL) partially control systemic viral replication and delay disease progression. Although available data has been provocative, the role of anti-HIV CTL in the CNS has received little attention. To fill this gap we will examine relationships between intrathecal viral replication, CTL responses, and glial activation/proliferation during HIV-1 infection. These studies will be relevant not only to AIDS but to other inflammatory diseases of the CNS as well.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'HIV-infected subjects who are at least 18 years of age, with no ART in the previous 3 months, and with plasma HIV-1 RNA \\>20,000 copies/mL. Individuals with past ART experience must have the ability to construct an ART regimen predicted to completely suppress plasma HIV-1 RNA, based on results of viral susceptibility testing that is done as a routine part of clinical practice.', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* (All subjects in Groups A1, A2 and B):\n* At least 18 years of age.\n* No more than one month of ART in the past.\n* No ART in the previous 3 months.\n* Platelet count \\>100,000 cells/mm3 on most recent determination within 60 days prior to first study lumbar puncture.\n* Normal prothrombin time (PT) and partial thromboplastin time (PTT) on most recent determination within 60 days prior to first study lumbar puncture.\n* Among individuals with past ART experience, the ability to construct an ART regimen predicted to completely suppress plasma HIV-1 RNA, based on results of viral susceptibility testing that is done as a routine part of clinical practice.\n* Plasma HIV-1 RNA \\>20,000 copies/mL.\n* Additional Inclusion Criteria for Groups A1 and A2.\n* Group A1:\n* CD4+ T cell count \\>200 cells/mm3.\n* CSF HIV-1 RNA \\>2,000 copies/mL on screening lumbar puncture.\n* No history of significant allergy to beta lactam antibiotics, including penicillins and cephalosporins.\n* No history of allergy to vancomycin.\n* Group A2:\n* CD4+ T cell count \\<200 cells/mm3.\n* CSF HIV-1 RNA \\>2,000 copies/mL on screening lumbar puncture.\n* No history of significant allergy to beta lactam antibiotics, including penicillins and cephalosporins.\n* No history of allergy to vancomycin.\n\nExclusion Criteria:\n\n* Evidence of CNS opportunistic infections or space occupying lesion.\n* History of significant CNS disorder unrelated to HIV infection such as trauma, congenital malformations or genetic disorders.\n* History of seizures.\n* As determined by the investigator, a significant active or previous history of cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, or endocrine disease(s) that would interfere with study participation.\n* Evidence or suspicion of vascular or Alzheimer's type dementias.\n* Evidence or suspicion of Parkinson's disease.\n* History of allergy to lidocaine.\n* Implanted metal objects that make MRI contraindicated. This may require consultation with colleagues in the Vanderbilt Dept. of Radiology.\n* Women who are pregnant or breastfeeding.\n* Women with a positive pregnancy test on enrollment or prior to study drug administration.\n* Women of childbearing potential (WOCBP) who are unwilling or unable to use an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.\n* Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study."}, 'identificationModule': {'nctId': 'NCT00583167', 'briefTitle': 'CNS (Central Nervous System) Viral Dynamics and Cellular Immunity During AIDS', 'organization': {'class': 'OTHER', 'fullName': 'Vanderbilt University'}, 'officialTitle': 'CNS Viral Dynamics and Cellular Immunity During AIDS', 'orgStudyIdInfo': {'id': '050001'}, 'secondaryIdInfos': [{'id': 'R01MH071205', 'link': 'https://reporter.nih.gov/quickSearch/R01MH071205', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'A1', 'description': 'HIV-infected subjects who are at least 18 years of age, with no ART in the previous 3 months, and with plasma HIV-1 RNA \\>20,000 copies/mL. CD4+ T cell count \\>200 cells/mm3. Group A1 will undergo continuous CSF ( cerebrospinal fluid) sampling via intrathecal catheter.'}, {'label': 'A2', 'description': 'HIV-infected subjects who are at least 18 years of age, with no ART in the previous 3 months, and with plasma HIV-1 RNA \\>20,000 copies/mL. CD4+ T cell count \\<200 cells/mm3. Group A2 will undergo continuous CSF sampling via intrathecal catheter.'}, {'label': 'B', 'description': 'HIV-infected subjects who are at least 18 years of age, with no ART in the previous 3 months, and with plasma HIV-1 RNA \\>20,000 copies/mL. Group B will not undergo continuous CSF sampling, but will undergo sparse CSF sampling by lumbar punctures.'}]}, 'contactsLocationsModule': {'locations': [{'zip': '37232-2582', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Vanderbilt AIDS Clinical Trials Center', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}], 'overallOfficials': [{'name': 'David W. Haas, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Vanderbilt University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Vanderbilt University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institutes of Health (NIH)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Medicine', 'investigatorFullName': 'David Haas', 'investigatorAffiliation': 'Vanderbilt University'}}}}