[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100476869":3},{"organization":4,"armGroups":7,"interventions":10,"overallOfficials":18,"centralContacts":23,"locations":33,"responsibleParty":104,"collaborators":107,"id":117,"slug":118,"hasResults":119,"nctId":120,"briefTitle":121,"officialTitle":122,"acronym":10,"eligibilityCriteria":123,"healthyVolunteers":119,"sex":124,"minAge":125,"maxAge":126,"enrollmentInfo":127,"targetDuration":10,"studyType":130,"phases":10,"briefSummary":131,"conditions":132,"keywords":138,"overallStatus":36,"whyStopped":10,"lastUpdateSubmitDate":144,"lastUpdatePostDateStruct":145,"startDateStruct":148,"completionDateStruct":150,"leadSponsor":152,"locationsCount":153},{"fullName":5,"class":6},"University of Texas Southwestern Medical Center","OTHER",[8,12,15],{"label":9,"type":10,"description":11,"interventionNames":10},"V122I TTR carriers",null,"Carriers and controls will undergo standardized, detailed CMRI assessments to test the hypothesis that V122I TTR carrier status will be associated with greater evidence of pathological amyloid progression in comparison with non-carriers.\n\nIn addition to the CMRI assessments, carriers and controls enrolled at UT Southwestern will undergo standardized exercise CMRI assessments during the same study visit.\n\nV122I TTR carriers will undergo detailed biomarker assessments. These will be compared with controls and patients with symptomatic V122I hATTR-CA .",{"label":13,"type":10,"description":14,"interventionNames":10},"Age-, sex-, and race-matched non-carrier controls","Carriers and controls will undergo standardized, detailed CMRI assessments to test the hypothesis that V122I TTR carrier status will be associated with greater evidence of pathological amyloid progression in comparison with non-carriers.\n\nIn addition to the CMRI assessments, carriers and controls enrolled at UT Southwestern will undergo standardized exercise CMRI assessments during the same study visit.\n\nControls will undergo detailed biomarker assessments. These will be compared with V122I TTR carriers and patients with symptomatic V122I hATTR-CA .",{"label":16,"type":10,"description":17,"interventionNames":10},"Patients with symptomatic V122I hATTR-CA","Patients with symptomatic V122I hATTR-CA will undergo detailed biomarker assessments. These will be compared with V122I TTR carriers and controls.",[19],{"name":20,"affiliation":21,"role":22},"Justin L Grodin, MD MPH","UT Southwestern","PRINCIPAL_INVESTIGATOR",[24,29],{"name":25,"role":26,"phone":27,"phoneExt":10,"email":28},"Amy Browning","CONTACT","214-645-8040","Amy.Browning@utsouthwestern.edu",{"name":30,"role":26,"phone":31,"phoneExt":10,"email":32},"Lori R Roth, MS, PAC","214-645-1043","Lori.Roth@utsouthwestern.edu",[34,61,85],{"facility":35,"status":36,"city":37,"state":37,"zip":38,"country":39,"countryCode":40,"cosmosGeoPoint":41,"geoPoint":46,"contacts":47},"Columbia University Medical Center","RECRUITING","New York","10032","United States","US",{"type":42,"coordinates":43},"Point",[44,45],-74.00597,40.71427,{"lat":45,"lon":44},[48,52,56,58],{"name":49,"role":26,"phone":50,"phoneExt":10,"email":51},"Samantha Guadalupe, MHA","(212) 932-4537","slg2172@cumc.columbia.edu",{"name":53,"role":26,"phone":54,"phoneExt":10,"email":55},"Jeffeny De Los Santos, MHA","(212) 932-4047","jd3456@cumc.columbia.edu",{"name":57,"role":22,"phone":10,"phoneExt":10,"email":10},"Mathew S Maurer, MD",{"name":59,"role":60,"phone":10,"phoneExt":10,"email":10},"Andrew J Einstein, MD PhD","SUB_INVESTIGATOR",{"facility":62,"status":36,"city":63,"state":64,"zip":65,"country":39,"countryCode":40,"cosmosGeoPoint":66,"geoPoint":70,"contacts":71},"Cleveland Clinic","Cleveland","Ohio","44195",{"type":42,"coordinates":67},[68,69],-81.69541,41.4995,{"lat":69,"lon":68},[72,76,77,79,81,83],{"name":73,"role":26,"phone":74,"phoneExt":10,"email":75},"Jennifer (Kirsop) Wilcox","216-636-6153","kirsopj@ccf.org",{"name":10,"role":26,"phone":74,"phoneExt":10,"email":10},{"name":78,"role":22,"phone":10,"phoneExt":10,"email":10},"W. H. Wilson Tang, MD",{"name":80,"role":60,"phone":10,"phoneExt":10,"email":10},"Deborah H Kwon, MD",{"name":82,"role":60,"phone":10,"phoneExt":10,"email":10},"Mazen Hanna, MD",{"name":84,"role":60,"phone":10,"phoneExt":10,"email":10},"Christopher Nguyen, MD",{"facility":5,"status":36,"city":86,"state":87,"zip":88,"country":39,"countryCode":40,"cosmosGeoPoint":89,"geoPoint":93,"contacts":94},"Dallas","Texas","75390",{"type":42,"coordinates":90},[91,92],-96.80667,32.78306,{"lat":92,"lon":91},[95,96,97,99,101,103],{"name":25,"role":26,"phone":27,"phoneExt":10,"email":28},{"name":20,"role":22,"phone":10,"phoneExt":10,"email":10},{"name":98,"role":60,"phone":10,"phoneExt":10,"email":10},"Julia Kozlitina, PhD",{"name":100,"role":60,"phone":10,"phoneExt":10,"email":10},"Markey McNutt, MD PhD",{"name":102,"role":60,"phone":10,"phoneExt":10,"email":10},"Vlad G Zaha, MD PhD",{"name":30,"role":60,"phone":10,"phoneExt":10,"email":10},{"type":22,"investigatorFullName":105,"investigatorTitle":106,"investigatorAffiliation":5,"oldNameTitle":10,"oldOrganization":10},"Justin Grodin","Associate Professor of Medicine",[108,110,112,114],{"name":109,"class":6},"The Cleveland Clinic",{"name":111,"class":6},"Columbia University",{"name":113,"class":6},"The University of Texas at Arlington",{"name":115,"class":116},"National Heart, Lung, and Blood Institute (NHLBI)","NIH","100476869","subclinical-transthyretin-cardiac-amyloidosis-in-v122i-ttr-carriers-100476869",false,"NCT05489549","Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers","Identifying Subclinical Transthyretin Cardiac Amyloidosis in Asymptomatic Carriers of the V122I TTR Allele","(V122I TTR carriers and carriers of other pathogenic TTR alleles (or matched non-carriers))\n\nInclusion Criteria:\n\n* Men and women ages 30-80 who are carriers of pathogenic TTR alleles (or matched non-carriers) without history of HF (this will be assessed by study personnel) and defined as: a) No history of hospitalization within the previous 12 months for management of HF; b) Without an elevated B-type natriuretic peptide level ≥100 pg\u002FmL or NT-proBNP ≥360 pg\u002FmL within the previous 12 months; or c) No clinical diagnosis of HF from a treating clinician\n* Signed informed consent\n\nExclusion Criteria:\n\n* A self-reported history or clinical history of HF\n* Other known causes of cardiomyopathy\n* History of light-chain cardiac amyloidosis\n* Prior type 1 myocardial infarction (non-ST segment elevation myocardial Infarction {NSTEMI} or ST-elevation myocardial infarction {STEMI})\n* Cardiac transplantation\n* Body weight \\>250 lbs\n* Estimated glomerular filtration rate ≤30 mL\u002Fmin\u002F1.73 m2\n* Inability to safely undergo CMRI\n\n(For participants with symptomatic hATTR-CA, we will enroll probands with HF from Aim 1 or patients with suspected symptomatic hATTR-CA from the three study sites.)\n\nInclusion Criteria:\n\n* Men and women ages 30-80 who have symptomatic hATTR-CA as determined by a history of HF (this will be assessed by study personnel) and defined as: a) History of hospitalization within the previous 12 months for management of HF; b) An elevated B-type natriuretic peptide level ≥100 pg\u002FmL or NT-proBNP ≥360 pg\u002FmL within the previous 12 months; or c) A clinical diagnosis of HF from a treating clinician.\n* Have an established or suspected diagnosis of hATTR-CA based on either a) Biopsy confirmed by Congo red (or equivalent) staining with tissue typing with immunohistochemistry or mass spectrometric analysis or immunoelectron microscopy, OR b) positive technetium-99m (99mTc)-pyrophosphate or -bisphosphonate scan, combined with accepted laboratory criteria without abnormal M-protein.\n* TTR gene sequencing that is pending or that is confirming the pathogenic TTR variant\n* Signed informed consent\n\nExclusion Criteria:\n\n* Other known causes of cardiomyopathy\n* History of light-chain cardiac amyloidosis\n* Cardiac transplantation\n* Liver transplantation\n* Previous treatment with a TTR stabilizer (tafamidis, acoramidis) within the prior 14 days or TTR any silencer (inotersen, patisiran, eplontersen)\n* Estimated glomerular filtration rate ≤30 mL\u002Fmin\u002F1.73 m2","ALL","30 Years","80 Years",{"count":128,"type":129},500,"ESTIMATED","OBSERVATIONAL","Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic specificity to detect early disease.\n\nThe overall objectives of this study are to determine the presence of subclinical hATTR-CA and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The central hypothesis of this proposal is that hATTR-CA has a long latency period that will be detected through subclinical amyloidosis imaging and biomarker phenotyping.\n\nThe central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim 1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2) determine the association between amyloid-specific biomarkers and V122I TTR carrier status; and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim 1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-, and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our clinical sites. These biomarkers detect and quantify different processes of TTR amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers to detect imaging evidence of subclinical hATTR-CA disease.",[133,134,135,136,137],"Amyloidosis, Hereditary","Amyloidosis Cardiac","Amyloidosis, Familial","Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy","Transthyretin Gene Mutation",[139,140,141,142,143],"Amyloidosis","Transthyretin Amyloidosis","V122I TTR","p.Val142Ile TTR","Cardiac magnetic resonance imaging","2026-06-23",{"date":146,"type":147},"2026-06-26","ACTUAL",{"date":149,"type":147},"2022-11-21",{"date":151,"type":129},"2027-06-30",{"name":5,"class":6},3]