Ignite Creation Date:
2025-12-24 @ 9:15 PM
Ignite Modification Date:
2026-01-01 @ 8:05 PM
Study NCT ID:
NCT01863004
Status:
TERMINATED
Last Update Posted:
2017-09-21
First Post:
2013-04-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'C537995', 'term': 'Dysferlinopathy'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069286', 'term': 'Bortezomib'}], 'ancestors': [{'id': 'D001897', 'term': 'Boronic Acids'}, {'id': 'D000148', 'term': 'Acids, Noncarboxylic'}, {'id': 'D000143', 'term': 'Acids'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D001896', 'term': 'Boron Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011719', 'term': 'Pyrazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 3}}, 'statusModule': {'whyStopped': 'insufficient enrollment rate', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2012-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-09', 'completionDateStruct': {'date': '2017-09-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-09-20', 'studyFirstSubmitDate': '2013-04-29', 'studyFirstSubmitQcDate': '2013-05-22', 'lastUpdatePostDateStruct': {'date': '2017-09-21', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2013-05-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-09-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Dysferlin protein expression levels change from baseline over 5 days assessed by repeated biopsies and blood draws in skeletal muscle and in blood monocytes following administration of a single dose of Bortezomib.', 'timeFrame': 'repeated needle muscle biopsies over a five day period', 'description': 'Repeated needle muscle biopsies and blood draws will be performed after administration of a single dose of Bortezomib (Velcade) to assess dysferlin protein expression in skeletal muscle and in blood monocytes over a five day period.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Dysferlinopathy']}, 'referencesModule': {'references': [{'pmid': '22318734', 'type': 'RESULT', 'citation': 'Azakir BA, Di Fulvio S, Kinter J, Sinnreich M. Proteasomal inhibition restores biological function of mis-sense mutated dysferlin in patient-derived muscle cells. J Biol Chem. 2012 Mar 23;287(13):10344-10354. doi: 10.1074/jbc.M111.329078. Epub 2012 Feb 8.', 'retractions': [{'pmid': '28754767', 'source': 'J Biol Chem. 2017 Jul 28;292(30):12542'}]}, {'pmid': '22174839', 'type': 'RESULT', 'citation': 'Di Fulvio S, Azakir BA, Therrien C, Sinnreich M. Dysferlin interacts with histone deacetylase 6 and increases alpha-tubulin acetylation. PLoS One. 2011;6(12):e28563. doi: 10.1371/journal.pone.0028563. Epub 2011 Dec 8.', 'retractions': [{'pmid': '29377932', 'source': 'PLoS One. 2018 Jan 29;13(1):e0192239'}]}, {'pmid': '22736764', 'type': 'RESULT', 'citation': 'Azakir BA, Di Fulvio S, Salomon S, Brockhoff M, Therrien C, Sinnreich M. Modular dispensability of dysferlin C2 domains reveals rational design for mini-dysferlin molecules. J Biol Chem. 2012 Aug 10;287(33):27629-36. doi: 10.1074/jbc.M112.391722. Epub 2012 Jun 26.', 'retractions': [{'pmid': '28754768', 'source': 'J Biol Chem. 2017 Jul 28;292(30):12543'}]}]}, 'descriptionModule': {'briefSummary': "Dysferlin is a protein with an important role in the repair of muscle surface membranes. Mutations in dysferlin cause different forms of muscular dystrophies. Dysferlinopathies are inherited in an autosomal recessive manner, and many patients with this disease harbor mis-sense mutations in at least one of their two pathogenic DYSF alleles. These patients have significantly reduced or absent dysferlin levels in skeletal muscle, suggesting that dysferlin encoded by mis-sense alleles is rapidly degraded by the cell's quality-control system. In a series of in-vitro experiments we showed that mis-sense mutated dysferlin can be salvaged from degradation by proteasomal inhibition. This resulted in an increase of functional dysferlin protein and a subsequent repair of plasma membranes of cultured patient-derived muscle cells. In this proof-of-concept study we would like to test wether proteasomal inhibition can salvage mis-sense mutated dysferlin in patients harboring certain dysferlin mis-sense mutations."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* must carry at least one allele of a salvageable mis-sense mutation of dysferlin\n* Age ≥ 18 years\n* Written informed consent\n\nExclusion Criteria:\n\n* Bleeding disorder\n* Acute or chronic kidney failure (CCL \\<50 ml/min)\n* Advanced liver disease or active hepatitis\n* Congestive heart failure NYHA III and IV\n* Pregnancy or nursing\n* Immunosuppression (prednisolone doses below 20 mg/d are allowed)\n* Therapy with strong inhibitors of cytochrome P450 3A4\n* HCV or HIV infection\n* Regular alcohol consumption (\\>14 drinks a week)\n* Drug addiction'}, 'identificationModule': {'nctId': 'NCT01863004', 'acronym': 'Dysferlin', 'briefTitle': 'Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Basel, Switzerland'}, 'officialTitle': 'Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin', 'orgStudyIdInfo': {'id': 'DYSF001A1'}, 'secondaryIdInfos': [{'id': '2011DR1148', 'type': 'REGISTRY', 'domain': 'Swissmedic Referenznummer 2011DR1148'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Bortezomib (Velcade®)', 'description': 'This study tests whether salvage of mis-sense mutated dysferlin through proteasomal inhibition seen in cultured muscle cells can be translated into patients harboring dysferlin mis-sense mutations. The proteasomal inhibitor Bortezomib (Velcade®) is already approved as a medication for the treatment of multiple myeloma in Switzerland and in other countries.\n\nFollowing an administration of a single dose of Bortezomib repeated needle muscle biopsies and blood draws will be performed to assess dysferlin levels in skeletal muscle and blood monocytes over a five day period.', 'interventionNames': ['Drug: Bortezomib']}], 'interventions': [{'name': 'Bortezomib', 'type': 'DRUG', 'otherNames': ['Velcade®'], 'armGroupLabels': ['Bortezomib (Velcade®)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '4031', 'city': 'Basel', 'country': 'Switzerland', 'facility': 'Neuromuskuläres Zentrum, Universitätsspital Basel', 'geoPoint': {'lat': 47.55839, 'lon': 7.57327}}], 'overallOfficials': [{'name': 'Michael Sinnreich, Prof. Dr. MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Sponsor-Investigator, Neuromuscular Center, Neurology Clinic, University Hospital Basel, Switzerland'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Basel, Switzerland', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}