Ignite Creation Date:
2025-12-24 @ 10:58 PM
Ignite Modification Date:
2026-02-11 @ 9:08 PM
Study NCT ID:
NCT02429869
Status:
COMPLETED
Last Update Posted:
2019-11-19
First Post:
2015-04-24
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068338', 'term': 'Everolimus'}], 'ancestors': [{'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Rodney.Rogers@ucsf.edu', 'phone': '415-514-6454', 'title': 'Rodney Rogers', 'organization': 'University of California, San Francisco'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'This study had several obvious limitations, such as concomitant use of other immunomodulatory medications that may have masked or altered the effects of mTOR inhibition on HIV persistence. Sample size was also limited.'}}, 'adverseEventsModule': {'timeFrame': '1 year', 'eventGroups': [{'id': 'EG000', 'title': 'Everolimus', 'description': 'Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'seriousEvents': [{'term': 'Gastritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Cell-associated HIV DNA', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Everolimus', 'description': 'This is a single arm study. Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen'}], 'classes': [{'title': 'Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '35', 'groupId': 'OG000', 'lowerLimit': '8', 'upperLimit': '173'}]}]}, {'title': 'Month 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '43', 'groupId': 'OG000', 'lowerLimit': '21', 'upperLimit': '417'}]}]}, {'title': 'Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '81', 'groupId': 'OG000', 'lowerLimit': '28', 'upperLimit': '210'}]}]}, {'title': 'Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '16', 'groupId': 'OG000', 'lowerLimit': '9', 'upperLimit': '804'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)', 'description': 'Peripheral blood mononuclear cells were isolated from whole blood using the Ficoll density gradient technique. Peripheral blood CD4 T cells were enriched by negative selection using antibody-coupled magnetic beads (Stem Cell Technologies) prior to simultaneous RNA and DNA isolation using cell-sparing protocols (AllPrep, Qiagen). Bulk CD4+ T cell or PBMC-associated HIV DNA and unspliced RNA were quantified using real-time PCR methods.The primer and probe sequences targeted conserved regions to enable quantification of a broad range of HIV subtypes. Values were normalized to DNA quantification of a human housekeeping gene (CCR5) in order to determine nucleic acid copies per million CD4+ T cell or PBMC as described. In addition to traditional quantitative PCR, a novel single-cell-in-droplet (scd)PCR method was used to quantify the absolute number or frequency of individual purified CD4+ T cells that express unspliced HIV RNA.', 'unitOfMeasure': 'nucleic acid copies per million cells', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'CD4+ T Cell count was not collected at Month 6 for one participant who did not show up for the visit.'}, {'type': 'SECONDARY', 'title': 'Cell-associated Total HIV RNA', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Everolimus', 'description': 'This is a single arm study. Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen'}], 'classes': [{'title': 'Baseline HIV RNA CD4+', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '423', 'groupId': 'OG000', 'lowerLimit': '148', 'upperLimit': '1702'}]}]}, {'title': 'Month 2 HIV RNA CD4+', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '310', 'groupId': 'OG000', 'lowerLimit': '228', 'upperLimit': '789'}]}]}, {'title': 'Month 6 HIV RNA CD4+', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '702', 'groupId': 'OG000', 'lowerLimit': '417', 'upperLimit': '1299'}]}]}, {'title': 'Month 12 HIV RNA CD4+', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '354', 'groupId': 'OG000', 'lowerLimit': '165', 'upperLimit': '633'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)', 'description': 'Peripheral blood mononuclear cells were isolated from whole blood using the Ficoll density gradient technique. Peripheral blood CD4 T cells were enriched by negative selection using antibody-coupled magnetic beads (Stem Cell Technologies) prior to simultaneous RNA and DNA isolation using cell-sparing protocols (AllPrep, Qiagen). Bulk CD4+ T cell or PBMC-associated HIV DNA and unspliced RNA were quantified using real-time PCR methods.The primer and probe sequences targeted conserved regions to enable quantification of a broad range of HIV subtypes. Values were normalized to DNA quantification of a human housekeeping gene (CCR5) in order to determine nucleic acid copies per million CD4+ T cell or PBMC as described. In addition to traditional quantitative PCR, a novel single-cell-in-droplet (scd)PCR method was used to quantify the absolute number or frequency of individual purified CD4+ T cells that express unspliced HIV RNA.', 'unitOfMeasure': 'nucleic acid copies per million cells', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'CD4+ T Cell count was not collected at Month 6 for one participant who did not show up for the visit.'}, {'type': 'SECONDARY', 'title': 'Plasma HIV RNA', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Everolimus', 'description': 'This is a single arm study. Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen'}], 'classes': [{'title': 'Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.291', 'groupId': 'OG000', 'lowerLimit': '0', 'upperLimit': '0.9283'}]}]}, {'title': 'Month 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.584', 'groupId': 'OG000', 'lowerLimit': '0', 'upperLimit': '1.547'}]}]}, {'title': 'Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.042', 'groupId': 'OG000', 'lowerLimit': '0.189', 'upperLimit': '2.05'}]}]}, {'title': 'Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.941', 'groupId': 'OG000', 'lowerLimit': '0.191', 'upperLimit': '1.576'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)', 'description': 'Plasma HIV RNA was quantified in a highly sensitive single-copy assay (SCA) using repetitive sampling in the Panther system (Hologic) at the Blood Systems Research Institute. Up to 18 replicates were tested for each sample in order to determine plasma RNA levels as low as 0.18 copies/mL.', 'unitOfMeasure': 'nucleic acid copies per million cells', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'CD4+ T Cell count was not collected at Month 6 for one participant who did not show up for the visit.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Everolimus', 'description': 'Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Ten HIV-infected adult solid organ transplant participants on stable ART and were taking non-mTOR based immune suppressive regimens for allograft rejection were recruited at the University of California, San Francisco in this open label, single-arm everolimus trial.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Everolimus', 'description': 'Subjects on mTOR inhibitor (everolimus) for 6 months, added to standard of care immunosuppressive regimen'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '58.5', 'groupId': 'BG000', 'lowerLimit': '48', 'upperLimit': '64'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2016-03-11', 'size': 411653, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2019-05-09T14:56', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-02-24', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-10', 'completionDateStruct': {'date': '2018-01-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-10-29', 'studyFirstSubmitDate': '2015-04-24', 'resultsFirstSubmitDate': '2019-05-17', 'studyFirstSubmitQcDate': '2015-04-24', 'lastUpdatePostDateStruct': {'date': '2019-11-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-10-29', 'studyFirstPostDateStruct': {'date': '2015-04-29', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-11-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-01-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Cell-associated HIV DNA', 'timeFrame': 'Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)', 'description': 'Peripheral blood mononuclear cells were isolated from whole blood using the Ficoll density gradient technique. Peripheral blood CD4 T cells were enriched by negative selection using antibody-coupled magnetic beads (Stem Cell Technologies) prior to simultaneous RNA and DNA isolation using cell-sparing protocols (AllPrep, Qiagen). Bulk CD4+ T cell or PBMC-associated HIV DNA and unspliced RNA were quantified using real-time PCR methods.The primer and probe sequences targeted conserved regions to enable quantification of a broad range of HIV subtypes. Values were normalized to DNA quantification of a human housekeeping gene (CCR5) in order to determine nucleic acid copies per million CD4+ T cell or PBMC as described. In addition to traditional quantitative PCR, a novel single-cell-in-droplet (scd)PCR method was used to quantify the absolute number or frequency of individual purified CD4+ T cells that express unspliced HIV RNA.'}], 'secondaryOutcomes': [{'measure': 'Cell-associated Total HIV RNA', 'timeFrame': 'Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)', 'description': 'Peripheral blood mononuclear cells were isolated from whole blood using the Ficoll density gradient technique. Peripheral blood CD4 T cells were enriched by negative selection using antibody-coupled magnetic beads (Stem Cell Technologies) prior to simultaneous RNA and DNA isolation using cell-sparing protocols (AllPrep, Qiagen). Bulk CD4+ T cell or PBMC-associated HIV DNA and unspliced RNA were quantified using real-time PCR methods.The primer and probe sequences targeted conserved regions to enable quantification of a broad range of HIV subtypes. Values were normalized to DNA quantification of a human housekeeping gene (CCR5) in order to determine nucleic acid copies per million CD4+ T cell or PBMC as described. In addition to traditional quantitative PCR, a novel single-cell-in-droplet (scd)PCR method was used to quantify the absolute number or frequency of individual purified CD4+ T cells that express unspliced HIV RNA.'}, {'measure': 'Plasma HIV RNA', 'timeFrame': 'Baseline, Month 2, Month 6, Month 12 (6 months post discontinuation of everolimus)', 'description': 'Plasma HIV RNA was quantified in a highly sensitive single-copy assay (SCA) using repetitive sampling in the Panther system (Hologic) at the Blood Systems Research Institute. Up to 18 replicates were tested for each sample in order to determine plasma RNA levels as low as 0.18 copies/mL.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['HIV', 'Kidney Transplant', 'Liver Transplant']}, 'referencesModule': {'references': [{'pmid': '32780519', 'type': 'DERIVED', 'citation': 'Henrich TJ, Schreiner C, Cameron C, Hogan LE, Richardson B, Rutishauser RL, Deitchman AN, Chu S, Rogers R, Thanh C, Gibson EA, Zarinsefat A, Bakkour S, Aweeka F, Busch MP, Liegler T, Baker C, Milush J, Deeks SG, Stock PG. Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study. Am J Transplant. 2021 May;21(5):1765-1779. doi: 10.1111/ajt.16244. Epub 2020 Sep 15.'}]}, 'descriptionModule': {'briefSummary': 'Zortress (everolimus), the 40-O-(2-hydroxyethyl)-derivative of rapamycin, is an mTOR inhibitor approved for rejection prophylaxis in kidney transplant recipients. mTOR inhibition may favorably impact the HIV viral reservoir, and we hypothesize that adding everolimus to the transplant immunosuppressive regimen of HIV positive transplant recipients will decrease HIV persistence in CD4+ lymphocytes.', 'detailedDescription': 'Open-label, single arm study that will enroll antiretroviral-treated HIV-infected adults who are doing well post-liver or post-kidney transplant who are eligible and willing to add everolimus to their immunosuppressive regimen (with a target trough level between 3-8 ng/ml). Calcineurin inhibitors will be decreased to obtain a 50% reduction in trough levels with the addition of everolimus. Subjects will be maintained on that regimen for 6 months.\n\nBiologic specimens for intensive immunology and virology studies will be obtained before, during and after exposure to everolimus. Samples will be analyzed at screening, baseline (prior to addition of everolimus), and at weeks 8 and 26 (while on everolimus), and week 52 (6 months post everolimus discontinuation).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Solid organ (kidney, kidney/pancreas, or liver) transplant recipient\n2. Male or female ≥ 18 years of age.\n3. Documentation of HIV-1 infection diagnosis as evidenced by any licensed ELISA and confirmation by Western Blot, or documented history of detectable HIV-1 RNA)\n4. HIV-1 plasma RNA \\<50 copies/ml for at least 2 years with at least one measurement per year and most recent viral load within 16 weeks of enrollment and study drug initiation. Episodes of a single HIV plasma RNA 50 - 500 copies/ml will not exclude participation if the subsequent HIV plasma RNA was \\<50 copies/ml.\n5. CD4+ T cell counts greater than 200 cell/µl within 16 weeks of enrollment and study drug initiation.\n6. Receiving combination antiretroviral therapy (at least 3 agents)\n7. Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.\n\nExclusion Criteria:\n\n1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.\n2. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.\n3. Patients who are intending to modify antiretroviral therapy in the next 6 months for any reason.\n4. Serious illness requiring hospitalization or parenteral antibiotics within preceding 3 months.\n5. A screening hemoglobin below 11.5 g/dL.\n6. A screening TSH consistent with hypothyroidism.\n7. Significant renal disease (eGFR \\< 60 ml/min) or acute nephritis\n8. Clinically active hepatitis as evidenced by clinical jaundice or Grade 2 or higher liver function test abnormalities.\n9. Hepatic cirrhosis or decompensated chronic liver disease.\n10. Concurrent treatment with immunomodulatory drugs, such an interferon-alpha, or exposure to any immunomodulatory drug in past 16 weeks (outside of standard immunosuppression)."}, 'identificationModule': {'nctId': 'NCT02429869', 'acronym': 'HIVTR-EVE', 'briefTitle': 'Impact of Everolimus on HIV Persistence Post Kidney or Liver Transplant', 'organization': {'class': 'OTHER', 'fullName': 'University of California, San Francisco'}, 'officialTitle': 'Impact of Everolimus on HIV Persistence Post Kidney (and Kidney/Pancreas) or Liver Transplant', 'orgStudyIdInfo': {'id': 'HIVTR-EVE'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Everolimus', 'interventionNames': ['Drug: everolimus']}], 'interventions': [{'name': 'everolimus', 'type': 'DRUG', 'otherNames': ['Zortress'], 'armGroupLabels': ['Everolimus']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California, San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of California, San Francisco', 'class': 'OTHER'}, 'collaborators': [{'name': 'amfAR, The Foundation for AIDS Research', 'class': 'OTHER'}, {'name': 'Novartis', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Surgery', 'investigatorFullName': 'Peter Stock', 'investigatorAffiliation': 'University of California, San Francisco'}}}}