[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100530585":3},{"organization":4,"outcomesModule":7,"designInfo":24,"detailedDescription":30,"studyPopulation":23,"armGroups":31,"interventions":38,"overallOfficials":43,"centralContacts":55,"locations":62,"responsibleParty":332,"collaborators":334,"id":338,"slug":23,"hasResults":339,"nctId":340,"briefTitle":341,"officialTitle":342,"acronym":343,"eligibilityCriteria":344,"healthyVolunteers":339,"sex":345,"minAge":23,"maxAge":23,"enrollmentInfo":346,"targetDuration":23,"studyType":349,"phases":350,"briefSummary":351,"conditions":352,"keywords":354,"overallStatus":65,"whyStopped":23,"lastUpdateSubmitDate":356,"lastUpdatePostDateStruct":357,"startDateStruct":360,"completionDateStruct":362,"leadSponsor":364,"locationsCount":365},{"fullName":5,"class":6},"Population Health Research Institute","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":16,"otherOutcomes":23},[9,13],{"measure":10,"description":11,"timeFrame":12},"ΔT-wave amplitude value","T-wave amplitude on first post-pause sinus beat subtracted by the T-wave amplitude on the last sinus beat prior to pacing","At time of pacing maneuver",{"measure":14,"description":15,"timeFrame":12},"ΔQT value","Absolute QT value on first post-pause sinus beat subtracted by the absolute QT value on the last sinus beat prior to pacing",[17,20],{"measure":18,"description":19,"timeFrame":12},"Absolute QT value","Absolute QT value on first post-pause sinus beat",{"measure":21,"description":22,"timeFrame":12},"Absolute T-wave amplitude","Absolute T-wave amplitude on first post-pause sinus beat",null,{"allocation":25,"interventionModel":26,"interventionModelDescription":23,"primaryPurpose":27,"observationalModel":23,"timePerspective":23,"maskingInfo":28},"NA","SINGLE_GROUP","DIAGNOSTIC",{"masking":29,"maskingDescription":23,"whoMasked":23},"NONE","RyR2 loss-of-function variants have recently been established as causative for a new disease termed calcium release deficiency syndrome (CRDS) that confers a risk of malignant ventricular arrhythmias and sudden cardiac death. RyR2 encodes the cardiac ryanodine receptor, the calcium release channel on the sarcoplasmic reticulum that mediates excitation-contraction coupling through calcium-induced calcium-release. In contrast to CRDS, pathogenic RyR2 gain-of-function variants result in an autosomal dominant form of catecholaminergic polymorphic ventricular tachycardia (CPVT). The adrenergic-mediated ventricular arrhythmias characteristic of CPVT can be readily reproduced on exercise stress testing (EST), making EST the standard clinical diagnostic tool for CPVT.\n\nIn contrast to CPVT, the CRDS clinical phenotype is concealed with standard cardiac testing tools and its diagnosis presently requires cellular-based in vitro confirmation that an RyR2 variant causes loss-of-function. Beyond the significant time delay associated with in vitro functional analysis, this testing requires specialized expertise that is not widely available and remains research-based, making it impractical for routine use in clinical care. In this overall context, it is likely that the vast majority of global CRDS cases have yet to be diagnosed.\n\nA prior report of an \"atypical CPVT\" family carrying an RyR2-p.M4109R variant observed marked and transient repolarization changes following pacing mediated tachycardia and a subsequent pause. Since publication of this report, in vitro characterization of the RyR2-p.M4109R variant has confirmed its being loss-of-function and the familial diagnosis has been revised to CRDS. Driven by these observations and promising preliminary findings, the DIAGNOSE CRDS study seeks to further investigate this apparent electrocardiographic signature of CRDS following brief tachycardia and subsequent pause as a potential method to clinically diagnose the condition.",[32],{"label":33,"type":34,"description":35,"interventionNames":36},"Pacing","EXPERIMENTAL","Separate ventricular and atrial pacing trains will be administered at different cycle lengths and the ventricular repolarization response on the first sinus beat following the subsequent pause will be evaluated.",[37],"Diagnostic Test: Pacing",[39],{"type":40,"name":33,"description":41,"armGroupLabels":42,"otherNames":23},"DIAGNOSTIC_TEST","1. Ventricular 10 beat burst at 500ms (120bpm)\n2. Ventricular 10 beat burst at 400ms (150bpm)\n3. Atrial 10 beat burst at 500ms (120bpm)\n4. Atrial 10 beat burst at 400ms (150bpm).",[33],[44,48,52],{"name":45,"affiliation":46,"role":47},"Ziv Dadon, MD","Shaare Zedek Medical Center","STUDY_DIRECTOR",{"name":49,"affiliation":50,"role":51},"Jason D Roberts, MD MAS","McMaster University","PRINCIPAL_INVESTIGATOR",{"name":53,"affiliation":54,"role":51},"Wayne Chen, PhD","University of Calgary",[56],{"name":57,"role":58,"phone":59,"phoneExt":60,"email":61},"Jason Roberts, MD MAS","CONTACT","905-297-3479","40632","jason.roberts@phri.ca",[63,84,98,112,128,141,156,169,183,193,206,219,232,245,259,272,287,303,316],{"facility":64,"status":65,"city":66,"state":67,"zip":68,"country":69,"countryCode":70,"cosmosGeoPoint":71,"geoPoint":76,"contacts":77},"University of California","RECRUITING","San Francisco","California","94143","United States","US",{"type":72,"coordinates":73},"Point",[74,75],-122.41942,37.77493,{"lat":75,"lon":74},[78,82],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},"Project Manager","905-521-2100","crds@phri.ca",{"name":83,"role":51,"phone":23,"phoneExt":23,"email":23},"Vasanth Vedantham, MD, PhD",{"facility":85,"status":65,"city":86,"state":87,"zip":88,"country":69,"countryCode":70,"cosmosGeoPoint":89,"geoPoint":93,"contacts":94},"Mayo Clinic","Rochester","Minnesota","55905",{"type":72,"coordinates":90},[91,92],-92.4699,44.02163,{"lat":92,"lon":91},[95,96],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":97,"role":51,"phone":23,"phoneExt":23,"email":23},"John Giudicessi, MD, PhD",{"facility":99,"status":65,"city":100,"state":101,"zip":102,"country":69,"countryCode":70,"cosmosGeoPoint":103,"geoPoint":107,"contacts":108},"University of Washington","Seattle","Washington","98195",{"type":72,"coordinates":104},[105,106],-122.33207,47.60621,{"lat":106,"lon":105},[109,110],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":111,"role":51,"phone":23,"phoneExt":23,"email":23},"Uyanga Batnyam, MD",{"facility":113,"status":65,"city":114,"state":115,"zip":116,"country":117,"countryCode":118,"cosmosGeoPoint":119,"geoPoint":123,"contacts":124},"Antwerp University Hospital","Edegem","Antwerp","2650","Belgium","BE",{"type":72,"coordinates":120},[121,122],4.44504,51.15662,{"lat":122,"lon":121},[125,126],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":127,"role":51,"phone":23,"phoneExt":23,"email":23},"Johan Saenen, MD, PhD",{"facility":129,"status":65,"city":130,"state":23,"zip":131,"country":117,"countryCode":118,"cosmosGeoPoint":132,"geoPoint":136,"contacts":137},"Universitair Ziekenhuis Brussel","Brussels","1090",{"type":72,"coordinates":133},[134,135],4.34878,50.85045,{"lat":135,"lon":134},[138,139],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":140,"role":51,"phone":23,"phoneExt":23,"email":23},"Luigi Pannone, MD",{"facility":54,"status":65,"city":142,"state":143,"zip":144,"country":145,"countryCode":146,"cosmosGeoPoint":147,"geoPoint":151,"contacts":152},"Calgary","Alberta","T2N 1N4","Canada","CA",{"type":72,"coordinates":148},[149,150],-114.08529,51.05011,{"lat":150,"lon":149},[153,154],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":155,"role":51,"phone":23,"phoneExt":23,"email":23},"Erkan Ilhan, MD",{"facility":157,"status":65,"city":158,"state":143,"zip":159,"country":145,"countryCode":146,"cosmosGeoPoint":160,"geoPoint":164,"contacts":165},"Alberta Health Services","Edmonton","T6G 2C8",{"type":72,"coordinates":161},[162,163],-113.46871,53.55014,{"lat":163,"lon":162},[166,167],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":168,"role":51,"phone":23,"phoneExt":23,"email":23},"Joseph Atallah, MD CM, MSc",{"facility":170,"status":65,"city":171,"state":172,"zip":173,"country":145,"countryCode":146,"cosmosGeoPoint":174,"geoPoint":178,"contacts":179},"Children's & Women's Health Centre of British Columbia","Vancouver","British Columbia","V6H 3N1",{"type":72,"coordinates":175},[176,177],-123.11934,49.24966,{"lat":177,"lon":176},[180,181],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":182,"role":51,"phone":23,"phoneExt":23,"email":23},"Shubhayan Sanatani, MD",{"facility":184,"status":65,"city":171,"state":172,"zip":185,"country":145,"countryCode":146,"cosmosGeoPoint":186,"geoPoint":188,"contacts":189},"The University of British Columbia","V6T 1Z3",{"type":72,"coordinates":187},[176,177],{"lat":177,"lon":176},[190,191],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":192,"role":51,"phone":23,"phoneExt":23,"email":23},"Thomas M Roston, MD",{"facility":194,"status":65,"city":195,"state":196,"zip":197,"country":145,"countryCode":146,"cosmosGeoPoint":198,"geoPoint":202,"contacts":203},"Hamilton General Hospital","Hamilton","Ontario","L8L 2X2",{"type":72,"coordinates":199},[200,201],-79.84963,43.25011,{"lat":201,"lon":200},[204,205],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":49,"role":51,"phone":23,"phoneExt":23,"email":23},{"facility":207,"status":65,"city":208,"state":196,"zip":209,"country":145,"countryCode":146,"cosmosGeoPoint":210,"geoPoint":214,"contacts":215},"London Health Sciences Centre - University Hospital","London","N6A 5A5",{"type":72,"coordinates":211},[212,213],-81.23304,42.98339,{"lat":213,"lon":212},[216,217],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":218,"role":51,"phone":23,"phoneExt":23,"email":23},"Habib R Khan, MD",{"facility":220,"status":65,"city":221,"state":196,"zip":222,"country":145,"countryCode":146,"cosmosGeoPoint":223,"geoPoint":227,"contacts":228},"Ottawa Heart Institute","Ottawa","K1Y 4W7",{"type":72,"coordinates":224},[225,226],-75.69812,45.41117,{"lat":226,"lon":225},[229,230],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":231,"role":51,"phone":23,"phoneExt":23,"email":23},"Simon Hansom, MD",{"facility":233,"status":65,"city":234,"state":196,"zip":235,"country":145,"countryCode":146,"cosmosGeoPoint":236,"geoPoint":240,"contacts":241},"Toronto General Hospital","Toronto","M5G 2C4",{"type":72,"coordinates":237},[238,239],-79.39864,43.70643,{"lat":239,"lon":238},[242,243],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":244,"role":51,"phone":23,"phoneExt":23,"email":23},"Michael H. Gollob, MD, FRCP(C)",{"facility":246,"status":65,"city":247,"state":248,"zip":249,"country":145,"countryCode":146,"cosmosGeoPoint":250,"geoPoint":254,"contacts":255},"Montréal Heart Institute","Montreal","Quebec","H1T 1C8",{"type":72,"coordinates":251},[252,253],-73.58781,45.50884,{"lat":253,"lon":252},[256,257],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":258,"role":51,"phone":23,"phoneExt":23,"email":23},"Rafik Tadros, MD PhD",{"facility":260,"status":65,"city":261,"state":248,"zip":262,"country":145,"countryCode":146,"cosmosGeoPoint":263,"geoPoint":267,"contacts":268},"Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval","Québec","G1V 4G5",{"type":72,"coordinates":264},[265,266],-71.21454,46.81228,{"lat":266,"lon":265},[269,270],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":271,"role":51,"phone":23,"phoneExt":23,"email":23},"Christian Steinberg, MD",{"facility":273,"status":65,"city":274,"state":23,"zip":275,"country":276,"countryCode":277,"cosmosGeoPoint":278,"geoPoint":282,"contacts":283},"Aarhus University Hospital","Aarhus","DK-8200 N","Denmark","DK",{"type":72,"coordinates":279},[280,281],10.21076,56.15674,{"lat":281,"lon":280},[284,285],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":286,"role":51,"phone":23,"phoneExt":23,"email":23},"Henrik Jensen, MD",{"facility":288,"status":65,"city":289,"state":290,"zip":291,"country":292,"countryCode":293,"cosmosGeoPoint":294,"geoPoint":298,"contacts":299},"CHU de Bordeaux","Bordeaux","New Aquitaine","33404","France","FR",{"type":72,"coordinates":295},[296,297],-0.58046,44.84124,{"lat":297,"lon":296},[300,301],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":302,"role":51,"phone":23,"phoneExt":23,"email":23},"Frédéric Sacher, MD",{"facility":46,"status":65,"city":304,"state":23,"zip":305,"country":306,"countryCode":307,"cosmosGeoPoint":308,"geoPoint":312,"contacts":313},"Jerusalem","9103102","Israel","IL",{"type":72,"coordinates":309},[310,311],35.21633,31.76904,{"lat":311,"lon":310},[314,315],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":45,"role":51,"phone":23,"phoneExt":23,"email":23},{"facility":317,"status":65,"city":318,"state":319,"zip":320,"country":321,"countryCode":322,"cosmosGeoPoint":323,"geoPoint":327,"contacts":328},"Oxford University Hospitals","Oxford","Oxfordshire","OX3 9DU","United Kingdom","UK",{"type":72,"coordinates":324},[325,326],-1.25596,51.75222,{"lat":326,"lon":325},[329,330],{"name":79,"role":58,"phone":80,"phoneExt":23,"email":81},{"name":331,"role":51,"phone":23,"phoneExt":23,"email":23},"Julian Ormerod, BM, Bch, FRCP",{"type":333,"investigatorFullName":23,"investigatorTitle":23,"investigatorAffiliation":23,"oldNameTitle":23,"oldOrganization":23},"SPONSOR",[335],{"name":336,"class":337},"Canadian Institutes of Health Research (CIHR)","OTHER_GOV","100530585",false,"NCT06188689","Evaluation of A Clinical Diagnostic Test for CRDS","Evaluation of a Clinical Diagnostic Test for Calcium Release Deficiency Syndrome: The DIAGNOSE CRDS Study","DIAGNOSE CRDS","Cohort 1: Calcium Release Deficiency Syndrome (CRDS) Cases\n\nInclusion criteria:\n\n• Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing\n\nExclusion criteria:\n\n• Unable to provide informed consent\n\nCohort 2: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Cases\n\nInclusion criteria:\n\n* Satisfy a clinical phenotype consistent with the Expert Consensus Statement\n* Presence of a confirmed or presumed pathogenic gain-of-function RyR2 variant OR homozygous or compound heterozygous for likely pathogenic\u002Fpathogenic CASQ2 variants\n\nExclusion criteria:\n\n* Unable to provide informed consent\n* Use of a QT prolonging medication, aside from flecainide, at the time of the burst pacing maneuvers\n\nCohort 3: Survivors of Unexplained Cardiac Arrest (UCA)\n\nInclusion criteria:\n\n* Cardiac arrest requiring cardioversion or defibrillation that remains unexplained following an ECG, echocardiogram, coronary assessment, cardiac MRI, and exercise treadmill test\n* Undergone genetic testing that includes screening of RyR2\\*\n\nExclusion criteria:\n\n* Unable to provide informed consent\n* Use of a QT prolonging medication at the time of the burst pacing maneuvers\n\n  * Among survivors of UCA that possess a rare RyR2 variant in the absence of a CPVT phenotype, in vitro functional testing will be performed in order to confirm it is not loss- or gain-of-function (and will be arranged through the laboratory of Dr. Wayne Chen at the University of Calgary).\n\nCohort 4: SVT controls\n\nInclusion criteria:\n\n• Undergoing an invasive electrophysiology study\n\nExclusion criteria:\n\n* Ventricular cardiomyopathy\n* Ventricular pre-excitation\n* Long QT syndrome\n* Use of a QT prolonging medication at the time of the EP study\n* Use of a Class I or Class III anti-arrhythmic drug at the time of the EP study\n* Known obstructive coronary artery disease (existing coronary stenosis \\>50%)\n* Unable to provide informed consent","ALL",{"count":347,"type":348},400,"ESTIMATED","INTERVENTIONAL",[25],"Calcium Release Deficiency Syndrome (CRDS) is a novel inherited arrhythmia syndrome secondary to RyR2 loss-of-function that confers a risk of sudden cardiac death. Diagnosis of CRDS presently requires cellular-based in vitro confirmation that an RyR2 variant causes loss-of-function. We hypothesize that CRDS can be diagnosed clinically through evaluation of the repolarization response to brief tachycardia, mediated by cardiac pacing, and a subsequent pause.",[353],"Calcium Release Deficiency Syndrome (CRDS)",[355],"cardiac arrhythmia, sudden cardiac death, cardiac ryanodine receptor, unexplained cardiac arrest","2026-05-28",{"date":358,"type":359},"2026-06-01","ACTUAL",{"date":361,"type":359},"2023-02-02",{"date":363,"type":348},"2028-03",{"name":5,"class":6},19]