Ignite Creation Date:
2025-12-25 @ 1:44 AM
Ignite Modification Date:
2025-12-26 @ 12:01 AM
Study NCT ID:
NCT00779194
Status:
COMPLETED
Last Update Posted:
2024-06-12
First Post:
2008-10-23
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Prospective Study of Rapamycin for the Treatment of SLE
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008180', 'term': 'Lupus Erythematosus, Systemic'}], 'ancestors': [{'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D020123', 'term': 'Sirolimus'}], 'ancestors': [{'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'perla@upstate.edu', 'phone': '3154644194', 'title': 'Andras Perl', 'organization': 'STATE UNIVERSITY OF NEW YORK'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'SLE Subjects Receiving the Study Drug', 'description': 'SLE Subjects receiving the study drug, Rapamune. Rapamycin: Rapamycin, is given to this group at a starting dose of 2 g/day', 'otherNumAtRisk': 40, 'deathsNumAtRisk': 40, 'otherNumAffected': 1, 'seriousNumAtRisk': 40, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Controls', 'description': 'Healthy control group donating blood only for immunobiological outcomes.', 'otherNumAtRisk': 56, 'deathsNumAtRisk': 56, 'otherNumAffected': 0, 'seriousNumAtRisk': 56, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Oral ulcer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 56}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Reduction of the Disease Activity as Measured by SLEDAI and BILAG Scores.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'SLE Subjects Receiving the Study Drug', 'description': 'SLE subjects receiving the study drug Rapamune. Rapamycin: Rapamycin, is given to this group at a starting dose of 2 mg/day.'}], 'classes': [{'title': 'SLEDAI', 'categories': [{'measurements': [{'value': '10.2', 'spread': '5.6', 'groupId': 'OG000'}]}]}, {'title': 'BILAG', 'categories': [{'measurements': [{'value': '28.4', 'spread': '12.4', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '1 year', 'description': 'The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and The British Isles Lupus Assessment Group (BILAG) are clinical tools for assessing disease activity in lupus erythematosus patients. These indices play a central role as core determinants in SLE Responder Index.\n\nSLEDAI, comprising 24 items, quantifies disease activity on a scale of 0 to 105. Higher scores indicate more severe disease activity, reflecting cumulative impact of clinical and laboratory variables.\n\nBILAG, a comprehensive assessment, encompasses 97 items organized into 9 organ domains. The scoring ranges from A to E:\n\nA: No activity B: Mild activity C: Moderate activity D: Severe activity E: Very severe activity Total BILAG score is sum of individual item scores across all domains, with a potential range from 0 (if all items are graded as A, denoting no activity) to 97 (if all items are graded as E, signifying very severe activity). A lower total BILAG score indicates less severe disease activity.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'SLE patients'}, {'type': 'SECONDARY', 'title': 'Decrease of the Amount of Prednisone Needed to Control Disease Activity in SLE Patients.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'SLE Subjects Receiving the Study Drug', 'description': 'SLE subjects receiving the study drug, Rapamune. Rapamycin: Rapamycin, is given to this group at a starting dose of 2 mg/day.'}], 'classes': [{'title': 'Prednisone dose upon enrollment at visit 1', 'categories': [{'measurements': [{'value': '24.3', 'spread': '4.7', 'groupId': 'OG000'}]}]}, {'title': 'Prednisone dose upon termination of the 12-month treatment period at visit 6', 'categories': [{'measurements': [{'value': '7.2', 'spread': '2.3', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '1 year', 'description': 'Secondary endpoints were prednisone dose required to control disease activity.\n\nThe average daily dosage of prednisone that was employed to control disease activity was diminished from 24.3±4.7 mg/day upon enrollment at visit 1 to 7.2±2.3 mg/day upon termination of the 12-month treatment period at visit 6.', 'unitOfMeasure': 'mg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'SLE patients'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'SLE Subjects Receiving the Study Drug', 'description': 'SLE subjects receiving the study drug, Rapamune.\n\nRapamycin: Rapamycin, is given to this group at a starting dose of 2 mg/day.'}, {'id': 'FG001', 'title': 'Controls', 'description': 'Healthy control group donating blood only for immunobiological outcomes.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '43'}, {'groupId': 'FG001', 'numSubjects': '56'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}, {'groupId': 'FG001', 'numSubjects': '56'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '14'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'BG000'}, {'value': '56', 'groupId': 'BG001'}, {'value': '96', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'SLE Subjects Receiving the Study Drug', 'description': 'SLE Subjects Receiving the Study Drug, Rapamune. Rapamycin: Rapamycin, is given to this group at a starting dose of 2mg/day.'}, {'id': 'BG001', 'title': 'Controls', 'description': 'Blood samples of healthy individuals were obtained as controls only for immunobiological outcomes.'}, {'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': '37', 'groupId': 'BG000'}, {'value': '55', 'groupId': 'BG001'}, {'value': '92', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '45', 'spread': '14', 'groupId': 'BG000'}, {'value': '45', 'spread': '12', 'groupId': 'BG001'}, {'value': '45', 'spread': '13', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '38', 'groupId': 'BG000'}, {'value': '51', 'groupId': 'BG001'}, {'value': '89', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '40', 'groupId': 'BG000'}, {'value': '56', 'groupId': 'BG001'}, {'value': '96', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'SLE patients and healthy controls (Blood samples of healthy individuals were obtained as controls only for immunobiological outcomes)'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 99}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2008-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-05', 'completionDateStruct': {'date': '2015-12-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-05-14', 'studyFirstSubmitDate': '2008-10-23', 'resultsFirstSubmitDate': '2023-11-20', 'studyFirstSubmitQcDate': '2008-10-23', 'lastUpdatePostDateStruct': {'date': '2024-06-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2024-05-14', 'studyFirstPostDateStruct': {'date': '2008-10-24', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2024-06-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2015-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Reduction of the Disease Activity as Measured by SLEDAI and BILAG Scores.', 'timeFrame': '1 year', 'description': 'The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and The British Isles Lupus Assessment Group (BILAG) are clinical tools for assessing disease activity in lupus erythematosus patients. These indices play a central role as core determinants in SLE Responder Index.\n\nSLEDAI, comprising 24 items, quantifies disease activity on a scale of 0 to 105. Higher scores indicate more severe disease activity, reflecting cumulative impact of clinical and laboratory variables.\n\nBILAG, a comprehensive assessment, encompasses 97 items organized into 9 organ domains. The scoring ranges from A to E:\n\nA: No activity B: Mild activity C: Moderate activity D: Severe activity E: Very severe activity Total BILAG score is sum of individual item scores across all domains, with a potential range from 0 (if all items are graded as A, denoting no activity) to 97 (if all items are graded as E, signifying very severe activity). A lower total BILAG score indicates less severe disease activity.'}], 'secondaryOutcomes': [{'measure': 'Decrease of the Amount of Prednisone Needed to Control Disease Activity in SLE Patients.', 'timeFrame': '1 year', 'description': 'Secondary endpoints were prednisone dose required to control disease activity.\n\nThe average daily dosage of prednisone that was employed to control disease activity was diminished from 24.3±4.7 mg/day upon enrollment at visit 1 to 7.2±2.3 mg/day upon termination of the 12-month treatment period at visit 6.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True}, 'conditionsModule': {'conditions': ['Systemic Lupus Erythematosus (SLE)']}, 'referencesModule': {'references': [{'pmid': '29551338', 'type': 'RESULT', 'citation': 'Lai ZW, Kelly R, Winans T, Marchena I, Shadakshari A, Yu J, Dawood M, Garcia R, Tily H, Francis L, Faraone SV, Phillips PE, Perl A. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet. 2018 Mar 24;391(10126):1186-1196. doi: 10.1016/S0140-6736(18)30485-9. Epub 2018 Mar 15.'}]}, 'descriptionModule': {'briefSummary': 'Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin. It involves multiple organs including the joints, skin, kidneys and central nervous system. The disease process is caused by a dysfunction of the immune system. The drugs currently used for the treatment of SLE are only partially effective and carry significant risks for side-effects. Patients that were resistant or intolerant to conventional medication have been effectively treated with Rapamycin and were able to decrease the amount of prednisone they needed.\n\nThe purpose of this study is to prospectively determine the therapeutic efficacy and mechanism of action of Rapamune in patients with SLE. Healthy subjects not receiving Rapamune will be asked to donate blood to serve as controls only for immunobiological outcomes.\n\nAs part of the research effort to understand the reason for the variations in the effects of treatment drugs by different individuals, a sub-study of the DNA makeup of subjects enrolled in the trial will also be done. The purpose of the sub-study is to possibly determine whether different responses to the drugs used to treat SLE have a correlation with the differences in the genetic makeup of the subjects.', 'detailedDescription': '43 SLE subjects and 56 healthy controls are being recruited. The study will last 1 year with 9 study visits from day 0 to day 360. The healthy controls only need to donate blood once.\n\nThe study drug, sirolimus, is taken by mouth at a starting dose of 2mg/day. The dose is adjusted to achieve blood levels in the range of 6-15 ng/ml (the levels found to be effective for preventing organ rejections).\n\nBlood samples are obtained before taking sirolimus, every two weeks for the first month, then every three months until 1 year, and then three months later to check the effect of discontinuing rapamycin. Each SLE subject will be asked to provide up to 100 ml (20 teaspoons) of blood at each visit. The first 6 visits will take place within 3 months and the remaining 3 visits every 3 months.\n\nRoutine laboratory work will be performed. Part of the blood drawn will be used for research and part will be used for routine lab work as part of standard of care.\n\nThe non-routine laboratory studies include:\n\n1. Assessment of mitochondrial function in intact T cells\n2. Analysis of mTOR activity, FKBP12 expression, and global gene expression in lupus T cells.\n3. Predictors of therapeutic efficacy of sirolimus in SLE.\n\nThe study drug levels will be checked at every visit. The non-routine laboratory studies will be performed at Visits 0 and 8 for SLE subjects and at Visit 0 for the healthy control subjects.\n\nHealthy control subjects will be matched by age (a decade or less), gender, and ethnic origin. They will be recruited and analyzed only for immunobiological outcomes on the same day as lupus subjects.\n\nAll subjects will sign an informed consent at visit 0. There is a separate informed consent for the main study, one for the SLE subjects and one for the Healthy Controls. The same subjects can participate in the genetic sub-study. They must sign another informed consent for the genetic sub-study, one for the SLE subjects and one for the Healthy Controls. There is no need for additional blood drawing since part of the blood drawn for the main study can be used for the genetic sub-study.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nFor SLE Subjects:\n\n* SLE patients who exhibit ongoing disease activity by SLEDAI greater or equal to 4.\n* SLE patients whose disease activity is controlled by administration of corticosteroids, most commonly, at least 10 mg/day of prednisone.\n* 18 years of age or older.\n* Updated vaccinations prior to study entry.\n* Use of effective contraception for male patients before, during and up to 12 weeks after sirolimus therapy.\n\nFor Healthy Control Subjects:\n\n* 18 years of age or older\n* Must be matched with one of the SLE patients enrolled in the study by age, gender and ethnic origin\n* Must not have any acute or chronic illness.\n\nExclusion Criteria:\n\nFor SLE Subjects:\n\n* Patients who are pregnant.\n* Patients with allergy or intolerance to sirolimus.\n* Patients with life-threatening manifestations of SLE.\n* Patients with proteinuria exceeding 500 mg/24 h or urine protein/creatine ratio \\>0.5.\n* Patients with total cholesterol \\> 300 mg/dl or triglyceride \\> 400 mg.dl will be excluded.\n* Patients with acute infection requiring antibiotics.\n* Patients on sirolimus who develop infections and require intravenous antibiotics and fail to show clinical improvement in 5 days.\n* Patients concurrently undergoing B cell-depleting therapy, cyclophosphamide, cyclosporine, and tacrolimus.\n* Patients who have received investigational biologic B-cell depleting products within one year of study initiation.\n* Patients with a history of chronic viral infections (e.g., HIV, hepatitis B, hepatitis C) or with a history of a malignancy (except non-melanoma skin cancer).\n* Due to interference with sirolimus metabolism, subjects will not be allowed to receive concomitant rifampin, ketoconazole,voriconazole, itraconazole, erythromycin, or clarithromycin during the study.\n* Patients with any type of interstitial lung disease.\n\nFor Healthy control Subjects:\n\n* Subjects who are pregnant.\n* Subjects with any acute or chronic illness.'}, 'identificationModule': {'nctId': 'NCT00779194', 'acronym': 'Rapamune', 'briefTitle': 'Prospective Study of Rapamycin for the Treatment of SLE', 'organization': {'class': 'OTHER', 'fullName': 'State University of New York - Upstate Medical University'}, 'officialTitle': 'Prospective Study of Rapamycin for the Treatment of SLE', 'orgStudyIdInfo': {'id': 'IRB#5658'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'SLE subjects', 'description': 'SLE subjects receiving the study drug, Rapamune.', 'interventionNames': ['Drug: Rapamycin']}], 'interventions': [{'name': 'Rapamycin', 'type': 'DRUG', 'otherNames': ['Rapamune', 'Sirolimus'], 'description': 'Rapamycin, is given to this group at a starting dose of 2 mg/day.', 'armGroupLabels': ['SLE subjects']}]}, 'contactsLocationsModule': {'locations': [{'zip': '13210', 'city': 'Syracuse', 'state': 'New York', 'country': 'United States', 'facility': 'SUNY Upstate Medical University', 'geoPoint': {'lat': 43.04812, 'lon': -76.14742}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'State University of New York - Upstate Medical University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Pfizer', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Medicine, Division Chief of Rheumatology', 'investigatorFullName': 'Andras Perl', 'investigatorAffiliation': 'State University of New York - Upstate Medical University'}}}}