Ignite Creation Date:
2025-12-24 @ 3:45 PM
Ignite Modification Date:
2026-01-06 @ 1:02 PM
Study NCT ID:
NCT00677092
Status:
COMPLETED
Last Update Posted:
2017-05-19
First Post:
2008-05-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Pilot Study of Imatinib Mesylate to Treat Nephrogenic Systemic Fibrosis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D054989', 'term': 'Nephrogenic Fibrosing Dermopathy'}, {'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}], 'ancestors': [{'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D005355', 'term': 'Fibrosis'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068877', 'term': 'Imatinib Mesylate'}], 'ancestors': [{'id': 'D001549', 'term': 'Benzamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001565', 'term': 'Benzoates'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D010879', 'term': 'Piperazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011743', 'term': 'Pyrimidines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'jonathan.kay@umassmemorial.org', 'phone': '508-793-6936', 'title': 'Jonathan Kay, MD', 'organization': 'University of Massachusetts Medical School'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for secondary outcome measure or adverse event data entry.'}}, 'adverseEventsModule': {'timeFrame': '6 Months', 'description': 'PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for adverse event data entry.', 'eventGroups': [{'id': 'EG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.', 'otherNumAtRisk': 0, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percentage Change From Baseline in the Modified Rodnan Skin Score (mRSS) to Assess Skin Tethering', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 milligrams (mg) orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.'}], 'classes': [{'categories': [{'measurements': [{'value': '-24', 'spread': '14', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Month 4', 'description': 'The modified Rodnan Skin Score is the accepted clinical measure of scleroderma skin activity. The investigator assessed the thickening of the skin using the modified Rodnan Skin Score through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Skin thickness was assessed on a scale of 0 to 3; 0 representing normal skin and 3 being severe thickening. The sum of the individual scores can range from 0 (normal) to 51 (severe thickening in all 17 areas). Percentage change is calculated as the Month 4 Score - Baseline Score/Baseline Score \\* 100. A negative percentage change indicates improvement.', 'unitOfMeasure': 'percentage change in mRSS score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All enrolled participants with Baseline and Month 4 data available for analysis.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Maximal Extension of Elbows and Knees', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.'}], 'timeFrame': 'Baseline and Month 4', 'reportingStatus': 'POSTED', 'populationDescription': 'PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for secondary outcome measure.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Histologic Appearance of Skin Biopsy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.'}], 'timeFrame': 'Baseline and Month 4', 'reportingStatus': 'POSTED', 'populationDescription': 'PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for secondary outcome measure.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Visual Analog Scale (VAS) for Pain', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.'}], 'timeFrame': 'Baseline and Month 4', 'reportingStatus': 'POSTED', 'populationDescription': 'PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for secondary outcome measure.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Health Assessment Questionnaire (HAQ) Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.'}], 'timeFrame': 'Baseline and Month 4', 'reportingStatus': 'POSTED', 'populationDescription': 'PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for secondary outcome measure.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Short Form 36 (SF-36) Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.'}], 'timeFrame': 'Baseline and Month 4', 'reportingStatus': 'POSTED', 'populationDescription': 'PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for secondary outcome measure.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if participant developed gastrointestinal intolerance or alopecia.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}]}, {'type': 'Received Study Treatment', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}]}, {'type': 'Death Prior to Receiving Treatment', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Imatinib Mesylate Treatment', 'description': 'Imatinib mesylate 400 mg orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '61.7', 'spread': '14.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All enrolled participants with available Baseline data.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 12}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-04', 'completionDateStruct': {'date': '2009-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-04-10', 'studyFirstSubmitDate': '2008-05-08', 'resultsFirstSubmitDate': '2017-04-10', 'studyFirstSubmitQcDate': '2008-05-12', 'lastUpdatePostDateStruct': {'date': '2017-05-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-04-10', 'studyFirstPostDateStruct': {'date': '2008-05-13', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-05-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2009-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage Change From Baseline in the Modified Rodnan Skin Score (mRSS) to Assess Skin Tethering', 'timeFrame': 'Baseline and Month 4', 'description': 'The modified Rodnan Skin Score is the accepted clinical measure of scleroderma skin activity. The investigator assessed the thickening of the skin using the modified Rodnan Skin Score through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Skin thickness was assessed on a scale of 0 to 3; 0 representing normal skin and 3 being severe thickening. The sum of the individual scores can range from 0 (normal) to 51 (severe thickening in all 17 areas). Percentage change is calculated as the Month 4 Score - Baseline Score/Baseline Score \\* 100. A negative percentage change indicates improvement.'}], 'secondaryOutcomes': [{'measure': 'Change From Baseline in Maximal Extension of Elbows and Knees', 'timeFrame': 'Baseline and Month 4'}, {'measure': 'Change From Baseline in Histologic Appearance of Skin Biopsy', 'timeFrame': 'Baseline and Month 4'}, {'measure': 'Change From Baseline in Visual Analog Scale (VAS) for Pain', 'timeFrame': 'Baseline and Month 4'}, {'measure': 'Change From Baseline in Health Assessment Questionnaire (HAQ) Score', 'timeFrame': 'Baseline and Month 4'}, {'measure': 'Change From Baseline in Short Form 36 (SF-36) Score', 'timeFrame': 'Baseline and Month 4'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Treatment', 'Chronic kidney disease', 'Fibrosing disorders', 'Imatinib mesylate'], 'conditions': ['Nephrogenic Systemic Fibrosis']}, 'referencesModule': {'references': [{'pmid': '17907148', 'type': 'BACKGROUND', 'citation': 'Todd DJ, Kagan A, Chibnik LB, Kay J. Cutaneous changes of nephrogenic systemic fibrosis: predictor of early mortality and association with gadolinium exposure. Arthritis Rheum. 2007 Oct;56(10):3433-41. doi: 10.1002/art.22925.'}, {'pmid': '18668587', 'type': 'BACKGROUND', 'citation': 'Kay J, High WA. Imatinib mesylate treatment of nephrogenic systemic fibrosis. Arthritis Rheum. 2008 Aug;58(8):2543-8. doi: 10.1002/art.23696.'}, {'pmid': '20959325', 'type': 'BACKGROUND', 'citation': 'Kay J, Czirjak L. Gadolinium and systemic fibrosis: guilt by association. Ann Rheum Dis. 2010 Nov;69(11):1895-7. doi: 10.1136/ard.2010.134791. No abstract available.'}, {'pmid': '24914072', 'type': 'BACKGROUND', 'citation': 'Schmidt-Lauber C, Bossaller L, Abujudeh HH, Vladimer GI, Christ A, Fitzgerald KA, Latz E, Gravallese EM, Marshak-Rothstein A, Kay J. Gadolinium-based compounds induce NLRP3-dependent IL-1beta production and peritoneal inflammation. Ann Rheum Dis. 2015 Nov;74(11):2062-9. doi: 10.1136/annrheumdis-2013-204900. Epub 2014 Jun 9.'}, {'pmid': '26768242', 'type': 'BACKGROUND', 'citation': 'Todd DJ, Kay J. Gadolinium-Induced Fibrosis. Annu Rev Med. 2016;67:273-91. doi: 10.1146/annurev-med-063014-124936.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine the efficacy of imatinib mesylate in reducing cutaneous thickening and tethering in patients with nephrogenic systemic fibrosis (NSF). The study will also work to assess the safety and tolerability of imatinib mesylate in patients with chronic kidney disease and NSF.', 'detailedDescription': 'Nephrogenic systemic fibrosis (NSF) is a recently described, extremely debilitating and painful condition that affects individuals with renal failure. Recent reports suggest an association between gadolinium exposure during magnetic resonance (MR) studies and the subsequent development of NSF in patients with chronic renal failure. NSF is characterized by rapidly progressive skin hardening, tethering and hyperpigmentation, predominantly on the extremities. Visceral involvement is rare. Skin biopsies of early NSF lesions demonstrate thickened collagen bundles, mucin deposition, angiogenesis and numerous dermal spindle cells that stain with antibodies to cluster of differentiation 34 (CD34) and procollagen. Cutaneous changes of NSF are present in up to 13% of individuals receiving hemodialysis. Among those patients with clinical evidence of NSF, the principle investigator of this protocol has recently reported that NSF is associated with increased early mortality at 24-months.\n\nThere is no proven therapy for this devastating disorder. Anecdotal reports have shown modest improvement in joint mobility and decreased skin thickening with extracorporeal photopheresis and pentoxyphylline.\n\nIncreased transforming growth factor (TGF)-beta1 messenger ribonucleic acid (mRNA) on immunostaining has been observed in skin, fascia and striated muscle. Imatinib mesylate, a tyrosine kinase inhibitor, prevents TGF-beta-induced stimulation of collagen and extracellular matrix protein synthesis as well as mRNA expression by normal fibroblasts. This observation led the principal investigator to evaluate imatinib mesylate 400 milligrams (mg) orally (p.o.) daily for 1 year in two participants with NSF. The result was significant softening of previously hardened skin with increased mobility of skin that previously had been tethered to the underlying fascia. After one month of imatinib mesylate, one of the two participants had a 20 degree reduction of his knee flexion contractures.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age \\> 18 years\n* Biopsy-proven NSF\n* Ability to give consent\n\nExclusion Criteria:\n\n* Known sensitivity to imatinib mesylate or to any of its components\n* Pregnant or lactating woman\n* Bullous dermatologic disease\n* Aspartate aminotransferase / alanine aminotransferase (AST/ALT) \\>3 x upper limit of normal\n* Severe congestive heart failure \\[New York Heart Association (NYHA) Class III or IV\\]\n* Patients who have received Gleevec in the past 12 months'}, 'identificationModule': {'nctId': 'NCT00677092', 'acronym': 'GENESYF', 'briefTitle': 'Pilot Study of Imatinib Mesylate to Treat Nephrogenic Systemic Fibrosis', 'organization': {'class': 'OTHER', 'fullName': 'Massachusetts General Hospital'}, 'officialTitle': 'An Open Label Phase 2 Pilot Study to Determine the Safety, Efficacy and Tolerability of Gleevec (Imatinib Mesylate) in the Treatment of Nephrogenic Systemic Fibrosis', 'orgStudyIdInfo': {'id': '2007-P-001945'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Imatinib Mesylate (IM) Treatment', 'description': 'Imatinib mesylate 400 milligrams (mg) orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.', 'interventionNames': ['Drug: Imatinib mesylate']}], 'interventions': [{'name': 'Imatinib mesylate', 'type': 'DRUG', 'otherNames': ['Gleevec'], 'description': '400 mg p.o. daily for 4 months. Dosage was reduced to 200 mg if participants develop gastrointestinal intolerance or alopecia.', 'armGroupLabels': ['Imatinib Mesylate (IM) Treatment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Jonathan Kay, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Massachusetts General Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Massachusetts General Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Novartis Pharmaceuticals', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Jonathan Kay, MD', 'investigatorAffiliation': 'Massachusetts General Hospital'}}}}