Ignite Creation Date:
2025-12-24 @ 9:39 PM
Ignite Modification Date:
2026-02-20 @ 6:45 PM
Study NCT ID:
NCT00672932
Status:
COMPLETED
Last Update Posted:
2013-07-05
First Post:
2008-04-29
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, '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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068898', 'term': 'Raltegravir Potassium'}], 'ancestors': [{'id': 'D011760', 'term': 'Pyrrolidinones'}, {'id': 'D011759', 'term': 'Pyrrolidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'rwprice@sfgh.ucsf.edu', 'phone': '415-206-4487', 'title': 'Richard W. Price, M.D.', 'organization': 'UCSF'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'The underlying hypothesis might not have actually been addressed because of the particular makeup of the subject group with minimal CNS infection and immunoactivation that left little room to discern a therapeutic effect.'}}, 'adverseEventsModule': {'timeFrame': '12 weeks', 'description': '6 subjects who rolled over to treatment after 12 weeks of no treatment were followed for an additional 12 weeks. 1 subject in the Raltegravir group was not included in other analyses because a pharmacological study showed no drug in either plasma or CSF.', 'eventGroups': [{'id': 'EG000', 'title': 'Raltegravir Group', 'description': 'The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.', 'otherNumAtRisk': 15, 'otherNumAffected': 0, 'seriousNumAtRisk': 15, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'No Augmented Treatment', 'description': 'Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.', 'otherNumAtRisk': 9, 'otherNumAffected': 0, 'seriousNumAtRisk': 9, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'SECONDARY', 'title': 'Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Raltegravir Group', 'description': 'The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.'}, {'id': 'OG001', 'title': 'No Augmented Treatment', 'description': 'Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.51', 'spread': '1.03', 'groupId': 'OG000'}, {'value': '0.66', 'spread': '1.20', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)', 'description': 'Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR.', 'unitOfMeasure': 'percentage of cells', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'One subject in the raltegravir group was censored when a pharmacological study showed no drug in either plasma (n=9) or CSF. Six subjects randomized to no drug later rolled over to receive raltegravir. Primary analysis treated the rollover subjects as independent and compared 14 intensified to 9 nonintensified subject experiences.'}, {'type': 'PRIMARY', 'title': 'Change in CSF Concentrations of Neopterin After 12 Weeks', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Raltegravir Group', 'description': 'The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.'}, {'id': 'OG001', 'title': 'No Augmented Treatment', 'description': 'Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.1', 'spread': '0.3', 'groupId': 'OG000'}, {'value': '0.3', 'spread': '1.1', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)', 'description': 'CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.', 'unitOfMeasure': 'nmol/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'One subject in the raltegravir group was censored when a pharmacological study showed no drug in either plasma (n=9) or CSF. Six subjects randomized to no drug later rolled over to receive raltegravir. Primary analysis treated the rollover subjects as independent and compared 14 intensified to 9 nonintensified subject experiences.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Raltegravir Group', 'description': 'The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.'}, {'id': 'FG001', 'title': 'No Augmented Treatment Then Optional Rollover', 'description': 'Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen. After 12 weeks, subjects in this group have the option to rollover into the raltegravir group for 12 weeks.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'Completed Initial 12-week Assignment', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'Provided Analyzable Blood and CSF Sample', 'achievements': [{'comment': 'one subject was censored when pharmacological study showed no drug in plasma or CSF', 'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'Rolled Over to Raltegravir', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'comment': '6 subjects randomized to no drug later rolled over to receive raltegravir', 'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Raltegravir Group', 'description': 'The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.'}, {'id': 'BG001', 'title': 'No Augmented Treatment', 'description': 'Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age Continuous', 'classes': [{'categories': [{'measurements': [{'value': '52.7', 'spread': '6.4', 'groupId': 'BG000'}, {'value': '54.3', 'spread': '5.3', 'groupId': 'BG001'}, {'value': '53.9', 'spread': '6.1', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2008-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-05', 'completionDateStruct': {'date': '2011-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-05-29', 'studyFirstSubmitDate': '2008-04-29', 'resultsFirstSubmitDate': '2012-06-18', 'studyFirstSubmitQcDate': '2008-05-02', 'lastUpdatePostDateStruct': {'date': '2013-07-05', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2013-05-29', 'studyFirstPostDateStruct': {'date': '2008-05-06', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-07-05', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2010-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in CSF Concentrations of Neopterin After 12 Weeks', 'timeFrame': 'three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)', 'description': 'CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.'}], 'secondaryOutcomes': [{'measure': 'Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR', 'timeFrame': 'three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)', 'description': 'Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['raltegravir', 'central nervous system (CNS)', 'HIV-1', 'AIDS', 'cerebrospinal fluid (CSF)', 'immunoactivation', 'antiretroviral therapy', 'suppression'], 'conditions': ['HIV Infections']}, 'referencesModule': {'references': [{'pmid': '22021620', 'type': 'RESULT', 'citation': 'Dahl V, Lee E, Peterson J, Spudich SS, Leppla I, Sinclair E, Fuchs D, Palmer S, Price RW. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis. 2011 Dec 15;204(12):1936-45. doi: 10.1093/infdis/jir667. Epub 2011 Oct 21.'}]}, 'descriptionModule': {'briefSummary': "This pilot study focuses on the persistence of central nervous system (CNS) immune activation that has been observed in the presence of 'effective' combination antiretroviral therapy (cART). Attention to this issue is based on the fear that chronic CNS immunoactivation can cause indolent brain injury that will eventually compromise brain function as patients survive for years on treatment. A leading hypothesis explaining this continued immunoactivation is that viral replication continues within the brain at a level too low for detection in cerebrospinal fluid (CSF), yet sufficient to stimulate local immunoactivation. Based on this hypothesis, we propose to use augmented treatment with raltegravir to test whether additional suppression of this hypothesized CNS HIV-1 replication will reduce continued CNS immunoactivation."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Capacity to provide informed consent.\n* Documented HIV-1 infection.\n* History of continuous cART treatment (with at least three drugs) for at least 2 years.\n* Documentation of 'undetectable' plasma HIV-1 RNA for at least 1 year.\n* HIV-1 RNA \\<50 copies/mL in plasma and CSF at screening visit.\n\nExclusion Criteria:\n\n* Contraindication to LP (suspicion of CNS mass lesion, bleeding diathesis, etc.).\n* Prior experience with raltegravir or contraindication to raltegravir treatment, including medication interactions that might compromise ongoing antiretroviral therapy or treatment of other conditions.\n* Active opportunistic infections or neurological diseases.\n* Other conditions or treatments likely to interfere with treatment or evaluation.\n* Hemoglobin \\< 10 Gm/dL.\n* Pregnant or anticipating pregnancy during study.\n* Active substance abuse.\n* Subjects taking rifampin, phenytoin, Phenobarbital or other drugs that accelerate raltegravir metabolism and might decrease its tissue concentrations."}, 'identificationModule': {'nctId': 'NCT00672932', 'briefTitle': 'Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients', 'organization': {'class': 'OTHER', 'fullName': 'University of California, San Francisco'}, 'officialTitle': 'Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients', 'orgStudyIdInfo': {'id': 'CCRC5004'}, 'secondaryIdInfos': [{'id': 'R01MH062701', 'link': 'https://reporter.nih.gov/quickSearch/R01MH062701', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'raltegravir group', 'description': 'The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.', 'interventionNames': ['Drug: raltegravir']}, {'type': 'NO_INTERVENTION', 'label': 'No augmented treatment', 'description': 'Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.'}], 'interventions': [{'name': 'raltegravir', 'type': 'DRUG', 'otherNames': ['Isentress'], 'description': '400 mg two times daily for three months', 'armGroupLabels': ['raltegravir group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94110', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'Ucsf Ccrc, Sfgh', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}], 'overallOfficials': [{'name': 'Richard Price, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, San Francisco'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of California, San Francisco', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Mental Health (NIMH)', 'class': 'NIH'}, {'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}