Nctid:
NCT06226987
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-10-04"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D000000795", "term"=>"Fabry Disease"}, {"id"=>"D000006331", "term"=>"Heart Diseases"}], "ancestors"=>[{"id"=>"D000013106", "term"=>"Sphingolipidoses"}, {"id"=>"D000020140", "term"=>"Lysosomal Storage Diseases, Nervous System"}, {"id"=>"D000020739", "term"=>"Brain Diseases, Metabolic, Inborn"}, {"id"=>"D000001928", "term"=>"Brain Diseases, Metabolic"}, {"id"=>"D000001927", "term"=>"Brain Diseases"}, {"id"=>"D000002493", "term"=>"Central Nervous System Diseases"}, {"id"=>"D000009422", "term"=>"Nervous System Diseases"}, {"id"=>"D000059345", "term"=>"Cerebral Small Vessel Diseases"}, {"id"=>"D000002561", "term"=>"Cerebrovascular Disorders"}, {"id"=>"D000014652", "term"=>"Vascular Diseases"}, {"id"=>"D000002318", "term"=>"Cardiovascular Diseases"}, {"id"=>"D000040181", "term"=>"Genetic Diseases, X-Linked"}, {"id"=>"D000030342", "term"=>"Genetic Diseases, Inborn"}, {"id"=>"D000008661", "term"=>"Metabolism, Inborn Errors"}, {"id"=>"D000008064", "term"=>"Lipidoses"}, {"id"=>"D000008052", "term"=>"Lipid Metabolism, Inborn Errors"}, {"id"=>"D000016464", "term"=>"Lysosomal Storage Diseases"}, {"id"=>"D000008659", "term"=>"Metabolic Diseases"}, {"id"=>"D000052439", "term"=>"Lipid Metabolism Disorders"}], "browseLeaves"=>[{"id"=>"M9419", "name"=>"Heart Diseases", "asFound"=>"Disease of the Heart", "relevance"=>"HIGH"}, {"id"=>"M4124", "name"=>"Fabry Disease", "asFound"=>"Fabry Disease", "relevance"=>"HIGH"}, {"id"=>"M15904", "name"=>"Sphingolipidoses", "relevance"=>"LOW"}, {"id"=>"M18871", "name"=>"Lysosomal Storage Diseases", "relevance"=>"LOW"}, {"id"=>"M5204", "name"=>"Brain Diseases", "relevance"=>"LOW"}, {"id"=>"M5205", "name"=>"Brain Diseases, Metabolic", "relevance"=>"LOW"}, {"id"=>"M22498", "name"=>"Brain Diseases, Metabolic, Inborn", "relevance"=>"LOW"}, {"id"=>"M5742", "name"=>"Central Nervous System Diseases", "relevance"=>"LOW"}, {"id"=>"M29437", "name"=>"Cerebral Small Vessel Diseases", "relevance"=>"LOW"}, {"id"=>"M5810", "name"=>"Cerebrovascular Disorders", "relevance"=>"LOW"}, {"id"=>"M17400", "name"=>"Vascular Diseases", "relevance"=>"LOW"}, {"id"=>"M24877", "name"=>"Genetic Diseases, X-Linked", "relevance"=>"LOW"}, {"id"=>"M23686", "name"=>"Genetic Diseases, Inborn", "relevance"=>"LOW"}, {"id"=>"M11641", "name"=>"Metabolism, Inborn Errors", "relevance"=>"LOW"}, {"id"=>"M11064", "name"=>"Lipidoses", "relevance"=>"LOW"}, {"id"=>"M11054", "name"=>"Lipid Metabolism, Inborn Errors", "relevance"=>"LOW"}, {"id"=>"M11639", "name"=>"Metabolic Diseases", "relevance"=>"LOW"}, {"id"=>"M27029", "name"=>"Lipid Metabolism Disorders", "relevance"=>"LOW"}, {"id"=>"T2169", "name"=>"Fabry Disease", "asFound"=>"Fabry Disease", "relevance"=>"HIGH"}, {"id"=>"T5335", "name"=>"Sphingolipidosis", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Heart and Blood Diseases", "abbrev"=>"BC14"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Nervous System Diseases", "abbrev"=>"BC10"}, {"name"=>"Diseases and Abnormalities at or Before Birth", "abbrev"=>"BC16"}, {"name"=>"Nutritional and Metabolic Diseases", "abbrev"=>"BC18"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}}, "protocolSection"=>{"designModule"=>{"studyType"=>"OBSERVATIONAL", "designInfo"=>{"timePerspective"=>"PROSPECTIVE", "observationalModel"=>"COHORT"}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>12}, "patientRegistry"=>false}, "statusModule"=>{"overallStatus"=>"RECRUITING", "startDateStruct"=>{"date"=>"2024-01-02", "type"=>"ACTUAL"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2024-07", "completionDateStruct"=>{"date"=>"2026-01-02", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-07-18", "studyFirstSubmitDate"=>"2024-01-17", "studyFirstSubmitQcDate"=>"2024-01-17", "lastUpdatePostDateStruct"=>{"date"=>"2024-07-22", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-01-26", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2026-01-02", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"PET imaging vs. oedema detected by MRI", "timeFrame"=>"Baseline", "description"=>"Concordance between 68Ga-DOTATATE PET signal and myocardial oedema on MRI assessed by T2-weighted imaging"}, {"measure"=>"PET imaging vs. fibrosis detected by MRI", "timeFrame"=>"Baseline", "description"=>"Concordance between 68Ga-DOTATATE PET signal and myocardial fibrosis detected by late gadolinium enhancement MRI"}]}, "oversightModule"=>{"oversightHasDmc"=>false, "isFdaRegulatedDrug"=>false, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"conditions"=>["Fabry Disease, Cardiac Variant"]}, "referencesModule"=>{"references"=>[{"pmid"=>"28385306", "type"=>"RESULT", "citation"=>"Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060."}, {"pmid"=>"36697134", "type"=>"RESULT", "citation"=>"Corovic A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jorgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM. Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis. J Am Coll Cardiol. 2023 Jan 31;81(4):336-354. doi: 10.1016/j.jacc.2022.10.034."}]}, "descriptionModule"=>{"briefSummary"=>"Better methods for early detection of cardiac involvement in Fabry disease are needed to inform clinical management decisions that can help prevent or slow the progression of cardiac complications. In the Molecular Imaging of Inflammation in Fabry Disease of the Heart study, the investigators will test the use of 68Ga-DOTATATE PET/MRI for identifying myocardial inflammation in patients with Fabry disease.", "detailedDescription"=>"Fabry disease (OMIM 30150) is caused by mutations in the gene (AGAL) encoding for the lysosomal enzyme α-galactosidase A. Diminished activity of this enzyme results in progressive accumulation of its substrate globotriaosylceramide (Gb3) in the lysosomes of various cell types, including vascular endothelial cells, cardiomyocytes, valvular fibrocytes, conduction cells. The involvement of the heart in Fabry disease results in rhythm disturbances, progressive hypertrophy and scarring of the left ventricle leading to diastolic and systolic dysfunction.\n\nConventional diagnostic methods such as electrocardiography, transthoracic echocardiography and even magnetic resonance imaging (MRI) are not sensitive enough to detect early damage to myocardial tissue in Fabry disease. Identifying subtle early changes, at a point when specific treatment may be optimized, is therefore an area of ongoing interest. Early perspectives on Fabry heart involvement concentrated on the left ventricular hypertrophy. Later the widespread use of Cardiac MRI introduced the role of fibrosis, as suggested by the appearance of late gadolinium enhancement (LGE) in characteristic areas of the myocardium. Most recently, detection of oedema by T2-weighted imaging and/or T2-mapping on MRI, as well as 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning have pointed to the possibility of focal inflammation as a causative factor in progression of the myocardial disease to replacement fibrosis, with its attendant risk of fatal arrhythmia and cardiac decompensation. Whether the oedema signal on MRI sequences truly represents tissue inflammation in Fabry disease and whether LGE fully corresponds to replacement fibrosis remains unknown. Circulating markers of inflammation and immune activation are elevated in Fabry cardiomyopathy, but no fully specific marker has yet been found to correspond to either myocardial focal oedema or LGE.\n\nAlthough MRI is important for diagnosis and risk stratification in patients with cardiac involvement in Fabry disease, findings such as LGE, myocardial oedema and native T1 mapping tell the clinician little that is specific about the underlying disease mechanisms. Moreover, early inflammatory changes may occur in Fabry disease before the manifestation of such abnormalities are detectable by MRI. By combining PET imaging of myocardial inflammation with detailed MRI assessments of cardiac function, structure and tissue characterisation, hybrid PET/MRI has the potential to offer a comprehensive non-invasive workup for patients with Fabry disease.\n\nPrevious work has shown that 68Ga-DOTA-(Tyr3)-octreotate (DOTATATE), a somatostatin receptor PET tracer used in oncology imaging, can be re-purposed to image inflammation in the cardiovascular system. This method could be of particular use in conditions associated with focal myocardial inflammation such as Fabry disease because of low physiological expression of somatostatin receptors in healthy heart muscle, and therefore low background PET signal. Here, the investigators will investigate the use of 68Ga-DOTATATE PET/MRI for identifying myocardial inflammation in patients with Fabry disease."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["ADULT", "OLDER_ADULT"], "minimumAge"=>"18 years", "samplingMethod"=>"PROBABILITY_SAMPLE", "studyPopulation"=>"Participants with cardiac involvement in Fabry disease assessed by MRI", "eligibilityCriteria"=>"Inclusion Criteria:\n\n* Male or female participants \\>18 years old\n* Able to give written, informed consent and to lie flat\n* Have Fabry disease based on molecular diagnosis (at a minimum, documented enzyme deficiency in males and documented pathogenic mutation in females)\n* Cardiac MRI within 3 years documenting cardiac involvement in Fabry disease (left ventricular hypertrophy and/or late gadolinium enhancement and/or myocardial oedema)\n\nExclusion Criteria:\n\n* Any other diagnosis associated with cardiac muscle inflammation, including myocarditis\n* Previous gene therapy\n* Contra-indication to MRI scanning or intravenous gadolinium contrast (prior contrast reaction or chronic kidney disease with eGFR \\<30 mL/min/1.73 m2)\n* Women of child bearing potential not using adequate contraception\n* Uncontrolled atrial fibrillation\n* Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study"}, "identificationModule"=>{"nctId"=>"NCT06226987", "briefTitle"=>"Molecular Imaging in Fabry Disease of the Heart", "organization"=>{"class"=>"OTHER", "fullName"=>"University of Cambridge"}, "officialTitle"=>"Molecular Imaging in Fabry Disease of the Heart", "orgStudyIdInfo"=>{"id"=>"A095007"}}, "armsInterventionsModule"=>{"armGroups"=>[{"label"=>"Fabry Disease with cardiac involvement", "interventionNames"=>["Diagnostic Test: 68Ga-DOTATATE PET/MRI"]}], "interventions"=>[{"name"=>"68Ga-DOTATATE PET/MRI", "type"=>"DIAGNOSTIC_TEST", "description"=>"PET/MRI scanning", "armGroupLabels"=>["Fabry Disease with cardiac involvement"]}]}, "contactsLocationsModule"=>{"locations"=>[{"zip"=>"CB2 0QQ", "city"=>"Cambridge", "state"=>"Cambridgeshire", "status"=>"RECRUITING", "country"=>"United Kingdom", "contacts"=>[{"name"=>"Patrick Deegan, MD", "role"=>"CONTACT"}], "facility"=>"Cambridge University Hospital NHS Foundation Trust", "geoPoint"=>{"lat"=>52.2, "lon"=>0.11667}}], "centralContacts"=>[{"name"=>"Jason M Tarkin, PhD MBBS", "role"=>"CONTACT", "email"=>"jt545@cam.ac.uk", "phone"=>"+44(0)1223331504"}]}, "ipdSharingStatementModule"=>{"ipdSharing"=>"NO"}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"University of Cambridge", "class"=>"OTHER"}, "collaborators"=>[{"name"=>"Sanofi", "class"=>"INDUSTRY"}], "responsibleParty"=>{"type"=>"PRINCIPAL_INVESTIGATOR", "investigatorTitle"=>"Wellcome Clinical Research Career Development Fellow & Honorary Consultant Cardiologist", "investigatorFullName"=>"Jason Tarkin", "investigatorAffiliation"=>"University of Cambridge"}}}}
