Ignite Creation Date:
2025-12-24 @ 11:14 PM
Ignite Modification Date:
2025-12-27 @ 7:32 AM
Study NCT ID:
NCT01257269
Status:
RECRUITING
Last Update Posted:
2023-10-11
First Post:
2010-12-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011697', 'term': 'Purpura, Thrombotic Thrombocytopenic'}, {'id': 'D013921', 'term': 'Thrombocytopenia'}, {'id': 'D000743', 'term': 'Anemia, Hemolytic'}], 'ancestors': [{'id': 'D011696', 'term': 'Purpura, Thrombocytopenic'}, {'id': 'D011693', 'term': 'Purpura'}, {'id': 'D001778', 'term': 'Blood Coagulation Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D057049', 'term': 'Thrombotic Microangiopathies'}, {'id': 'D001791', 'term': 'Blood Platelet Disorders'}, {'id': 'D000095542', 'term': 'Cytopenia'}, {'id': 'D019851', 'term': 'Thrombophilia'}, {'id': 'D006470', 'term': 'Hemorrhage'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012877', 'term': 'Skin Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D000740', 'term': 'Anemia'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D019370', 'term': 'Observation'}], 'ancestors': [{'id': 'D008722', 'term': 'Methods'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Whole blood and plasma'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'OTHER', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 450}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2006-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-10', 'completionDateStruct': {'date': '2030-10', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-10-10', 'studyFirstSubmitDate': '2010-12-06', 'studyFirstSubmitQcDate': '2010-12-08', 'lastUpdatePostDateStruct': {'date': '2023-10-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2010-12-09', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2030-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical presentation and disease course in hereditary TTP', 'timeFrame': 'every year until death'}], 'secondaryOutcomes': [{'measure': 'Identification of disease-modifying factors, including genotype-phenotype correlation', 'timeFrame': 'every year until death'}, {'measure': 'Treatment requirements in hereditary TTP patients', 'timeFrame': 'every year until death'}, {'measure': 'Documentation of potential adversary effects of (long-term) plasma treatment', 'timeFrame': 'every year until death'}, {'measure': 'Mortality of hereditary TTP', 'timeFrame': 'every year until death'}, {'measure': 'Clinical course in family members', 'timeFrame': 'every year until death'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Thrombotic thrombocytopenic purpura', 'ADAMTS13', 'Von Willebrand factor', 'Von Willebrand factor cleaving protease', 'Thrombocytopenia', 'Hemolytic anemia'], 'conditions': ['Thrombotic Thrombocytopenic Purpura', 'Congenital Thrombotic Thrombocytopenic Purpura', 'Familial Thrombotic Thrombocytopenic Purpura', 'Thrombotic Thrombocytopenic Purpura, Congenital', 'Upshaw-Schulman Syndrome']}, 'referencesModule': {'references': [{'pmid': '33649760', 'type': 'DERIVED', 'citation': 'Tarasco E, Butikofer L, Friedman KD, George JN, Hrachovinova I, Knobl PN, Matsumoto M, von Krogh AS, Aebi-Huber I, Cermakova Z, Gorska-Kosicka M, Jalowiec KA, Largiader CR, Prohaszka Z, Sinkovits G, Windyga J, Lammle B, Kremer Hovinga JA. Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura. Blood. 2021 Jun 24;137(25):3563-3575. doi: 10.1182/blood.2020009801.'}, {'pmid': '30792199', 'type': 'DERIVED', 'citation': 'van Dorland HA, Taleghani MM, Sakai K, Friedman KD, George JN, Hrachovinova I, Knobl PN, von Krogh AS, Schneppenheim R, Aebi-Huber I, Butikofer L, Largiader CR, Cermakova Z, Kokame K, Miyata T, Yagi H, Terrell DR, Vesely SK, Matsumoto M, Lammle B, Fujimura Y, Kremer Hovinga JA; Hereditary TTP Registry. The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017. Haematologica. 2019 Oct;104(10):2107-2115. doi: 10.3324/haematol.2019.216796. Epub 2019 Feb 21.'}, {'pmid': '26830967', 'type': 'DERIVED', 'citation': 'Fan X, Kremer Hovinga JA, Shirotani-Ikejima H, Eura Y, Hirai H, Honda S, Kokame K, Taleghani MM, von Krogh AS, Yoshida Y, Fujimura Y, Lammle B, Miyata T. Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency. Int J Hematol. 2016 Mar;103(3):283-91. doi: 10.1007/s12185-015-1933-7. Epub 2016 Feb 1.'}, {'pmid': '25655456', 'type': 'DERIVED', 'citation': 'Lammle B. VWF and complement. Blood. 2015 Feb 5;125(6):896-8. doi: 10.1182/blood-2014-12-612556. No abstract available.'}, {'pmid': '23715103', 'type': 'DERIVED', 'citation': 'Mansouri Taleghani M, von Krogh AS, Fujimura Y, George JN, Hrachovinova I, Knobl PN, Quist-Paulsen P, Schneppenheim R, Lammle B, Kremer Hovinga JA. Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry. Hamostaseologie. 2013 May 29;33(2):138-43. doi: 10.5482/HAMO-13-04-0026.'}], 'seeAlsoLinks': [{'url': 'http://www.ttpregistry.net', 'label': 'Additional information'}]}, 'descriptionModule': {'briefSummary': 'Hereditary thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) is a rare disorder characterized by thrombocytopenia as a result of platelet consumption, microangiopathic hemolytic anemia, occlusion of the microvasculature with von Willebrand factor-platelet-thrombic and ischemic end organ damage. The underlying patho-mechanism is a severe congenital ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) deficiency which is the result of compound heterozygous or homozygous ADAMTS13 gene mutations.\n\nAlthough considered a monogenic disorder the clinical presentation in Upshaw-Schulman syndrome patients varies considerably without an apparent genotype-phenotype correlation. In 2006 we have initiated a registry for patients with Upshaw-Schulman syndrome and their family members to identify possible triggers of acute bouts of TTP, to document individual clinical courses and treatment requirements as well as possible side effects of long standing plasma substitution, e.g. alloantibody formation or viral infections.', 'detailedDescription': 'Background\n\nThrombocytopenia and microangiopathic hemolytic anemia together with a severely deficient ADAMTS13 activity confirm the diagnosis of acute thrombotic thrombocytopenic purpura (TTP). Today two forms of classical TTP are distinguished. The acquired form is caused by circulating auto-antibodies, mainly Immunoglobulin G (IgG), inhibiting ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) activity. In contrast, hereditary TTP, also known as Upshaw-Schulman syndrome (USS); #274150 Online Mendelian Inheritance in Man (OMIM), is the result of severe constitutional deficiency of ADAMTS13 due to compound heterozygous or homozygous mutations in the ADAMTS13 gene.\n\nThe clinical course of USS is variable with rather mild courses in some of the patients requiring plasma infusions only in special situations (i.e. pregnancy), while in others severe courses with important sequelae and even death in early childhood occur. The reasons for the variable clinical presentation and treatment requirements have not been elucidated. It seems likely, that additional, hitherto unidentified factors besides severe ADAMTS13 deficiency modify the clinical course.\n\nAt present, the clinical symptoms and laboratory values on which to base treatment regimens for hereditary TTP are poorly understood. Furthermore, increasing awareness of hereditary TTP results in rising numbers of patients in need of treatment and/or prophylaxis. However, currently very little is known on side effects of long standing plasma substitution. Alloimmunization with the formation of antibodies acting as inhibitors of treatment are well known in other congenital coagulation factor deficiencies (e.g. hemophilia A), but so far no case of treated hereditary TTP with subsequent antibody formation has been reported. It is the aim of the hereditary TTP Registry to provide information on the clinical course of the disease in as many patients as possible and therefore help to establish recommendations on the necessity, modalities, and risks of prophylactic plasma therapy in patients with hereditary TTP. Furthermore, it will help to gain detailed insight into triggers and risk factors of acute bouts of TTP.\n\nMoreover, the hereditary TTP Registry will provide information for family members on their risk to develop TTP-like or TTP-related disorders.\n\nObjective\n\nPrimary objective: Collection of as much information as possible on the clinical presentation, disease course, disease-modifying factors, and treatment modalities of patients suffering from hereditary thrombotic thrombocytopenic purpura (TTP).\n\nSecondary objective: To document potential adversary effects of (long-term) plasma treatment in patients with hereditary thrombotic thrombocytopenic purpura (TTP).\n\nMethods\n\nThe TTP Registry is designed to collect both retrospective and prospective clinical, molecular, and observational data on patients with confirmed or suspected hereditary TTP. Additionally, the Registry will collect data from family members of TTP patients enrolled in the Registry. The Registry will enroll as many confirmed or suspected hereditary TTP patients and their family members as possible; there is no cap on enrollment. The Registry enrollment and follow-up periods are open-ended. The endpoints for patients with confirmed or suspected hereditary TTP and family members are death or withdrawal of consent.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with either confirmed or with suspected hereditary TTP and their family members are eligible for enrollment', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Severe ADAMTS13 deficiency ( ≤ 10% activity) and no ADAMTS 13 inhibitor on two or more occasions at least one month apart\n* Being a family member of a confirmed or suspected patient\n* Molecular analysis of ADAMTS13 gene with one or more mutations and/or positive infusion trial (full recovered ADAMTS13 activity after infused fresh frozen plasma (FFP) with a plasma half-life of 2-4 days)'}, 'identificationModule': {'nctId': 'NCT01257269', 'acronym': 'TTP registry', 'briefTitle': 'Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)', 'organization': {'class': 'OTHER', 'fullName': 'Insel Gruppe AG, University Hospital Bern'}, 'officialTitle': 'Thrombotic Thrombocytopenic Purpura Registry - A Prospective Observational Study for Patients Suffering From Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)', 'orgStudyIdInfo': {'id': '031/06'}}, 'armsInterventionsModule': {'armGroups': [{'label': '1', 'description': 'Patients with confirmed hereditary TTP due to congenital ADAMTS13 deficiency', 'interventionNames': ['Other: Observation']}, {'label': '2', 'description': 'Family members of patients with confirmed hereditary TTP', 'interventionNames': ['Other: Observation']}], 'interventions': [{'name': 'Observation', 'type': 'OTHER', 'description': 'No interventions planned: treatment of patients at the discretion of the treating/responsible physician', 'armGroupLabels': ['1', '2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '73126-0901', 'city': 'Oklahoma City', 'state': 'Oklahoma', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'James N. George, M.D.', 'role': 'CONTACT', 'email': 'james-george@ouhsc.edu', 'phone': '405-271-4222'}, {'name': 'James N. George, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of Oklahoma Health Sciences Center, Department of Medicine, PO Box 26901', 'geoPoint': {'lat': 35.46756, 'lon': -97.51643}}, {'zip': 'A-1090', 'city': 'Vienna', 'status': 'RECRUITING', 'country': 'Austria', 'contacts': [{'name': 'Paul N. Knoebl, M.D.', 'role': 'CONTACT', 'email': 'paul.knoebl@meduniwien.ac.at', 'phone': '+43 1 40400 4410'}, {'name': 'Paul N. Knoebl, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Medical University of Vienna, Department of Medicine 1, Div. Hematology and Hemostasis Waehringer Guertel 18-20', 'geoPoint': {'lat': 48.20849, 'lon': 16.37208}}, {'zip': 'CZ-12820', 'city': 'Prague', 'status': 'RECRUITING', 'country': 'Czechia', 'contacts': [{'name': 'Ingrid Hrachovinova, Ph.D.', 'role': 'CONTACT', 'email': 'Ingrid.Hrachovinova@uhkt.cz', 'phone': '+420 2 2197 271'}, {'name': 'Ingrid Hrachovinova, Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Institute of Hematology and Blood Transfusion, Coagulation Laboratory, U nemocnice 1', 'geoPoint': {'lat': 50.08804, 'lon': 14.42076}}, {'zip': 'D-20246', 'city': 'Hamburg', 'status': 'NOT_YET_RECRUITING', 'country': 'Germany', 'contacts': [{'name': 'Reinhard Schneppenheim, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'schneppenheim@uke.de', 'phone': '+49 40 7410 54270'}, {'name': 'Reinhard Schneppenheim, M.D., Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University Medical Center Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Martinistr 52', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'zip': '634-8522', 'city': 'Kashihara', 'state': 'Nara', 'status': 'RECRUITING', 'country': 'Japan', 'contacts': [{'name': 'Yoshihiro Fujimura, M.D.', 'role': 'CONTACT', 'email': 'yoshifuji325@naramed-u.ac.jp', 'phone': '+81 744 22 3051', 'phoneExt': '3289'}, {'name': 'Yoshihiro Fujimura, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Nara Medical University, Department of Blood Transfusion Medicine, Shijyo-cho 840', 'geoPoint': {'lat': 33.95, 'lon': 135.78333}}, {'zip': 'NO-7006', 'city': 'Trondheim', 'status': 'RECRUITING', 'country': 'Norway', 'contacts': [{'name': 'Petter Quist-Paulsen, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'Petter.Quist-Paulsen@stolav.no', 'phone': '+47 815 55 850'}, {'name': 'Anne-Sophie von Krogh, M.D.', 'role': 'CONTACT', 'email': 'Anne-Sophie.von.Krogh@stolav.no', 'phone': '+47 815 55 850'}, {'name': 'Petter Quist-Paulsen, M.D.,Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Anne-Sophie von Krogh, M.D.', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Trondheim University St Olavs Hospital, Department of Hematology, PO Box 3250 Sluppen', 'geoPoint': {'lat': 63.43049, 'lon': 10.39506}}, {'zip': '3010', 'city': 'Bern', 'status': 'RECRUITING', 'country': 'Switzerland', 'contacts': [{'name': 'Johanna A Kremer Hovinga, MD', 'role': 'CONTACT', 'email': 'johanna.kremer@insel.ch', 'phone': '+41 31 632 02 65'}, {'name': 'Isabella Aebi, BMA', 'role': 'CONTACT', 'email': 'isabella.aebi-huber@insel.ch', 'phone': '+41 31 632 77 16'}, {'name': 'Johanna A Kremer Hovinga, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital and the University of Bern, Inselspital', 'geoPoint': {'lat': 46.94809, 'lon': 7.44744}}], 'centralContacts': [{'name': 'Johanna A Kremer Hovinga, MD', 'role': 'CONTACT', 'email': 'johanna.kremer@insel.ch', 'phone': '+41 31 632 02 65'}, {'name': 'Marissa Schraner, Ph.D.', 'role': 'CONTACT', 'email': 'marissa.schraner@insel.ch', 'phone': '+41 31 632 56 90'}], 'overallOfficials': [{'name': 'Johanna A Kremer Hovinga, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital and the University of Bern, Inselspital'}, {'name': 'Bernhard Lämmle, M.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'University Medical Center, Center for Thrombosis and Hemostasis, Mainz, Germany'}, {'name': 'Yoshihiro Fujimura, M.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan'}, {'name': 'Ingrid Hrachovinova, Ph.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'Institute of Hematology and Blood Transfusion, Coagulation Laboratory, Prague, Czech Republic'}, {'name': 'Petter Quist-Paulsen, M.D., Ph.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'Department of Hematology, St Olavs Hospital, 7006 Trondheim, Norway'}, {'name': 'Reinhard Schneppenheim, M.D., Ph.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany'}, {'name': 'James N. George, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'University of Oklahoma Health Sciences Center, Department of Medicine, United States of America'}, {'name': 'Paul N Knoebl, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Medical University of Vienna, Div. Hematology and Hemostasis, Austria'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Insel Gruppe AG, University Hospital Bern', 'class': 'OTHER'}, 'collaborators': [{'name': 'Swiss National Science Foundation', 'class': 'OTHER'}, {'name': 'Mach Gaensslen Foundation', 'class': 'OTHER'}, {'name': 'Baxalta Innovations GmbH, Wien, Austria', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}