Clinical trial NCT01322165: National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
Official title: National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Marfan Syndrome
Turner Syndrome
Ehlers-Danlos Syndrome
Loeys-Dietz Syndrome
FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 Genetic Mutation
Bicuspid Aortic Valve Without Known Family History
Bicuspid Aortic Valve With Family History
Bicuspid Aortic Valve With Coarctation
Familial Thoracic Aortic Aneurysm and Dissections
Shprintzen-Goldberg Syndrome
Other Aneur/Diss of Thoracic Aorta Not Due to Trauma, <50yo
Other Congenital Heart Disease
Keywords: Marfan syndrome
Turner syndrome
Bicuspid aortic valve
Ehlers-Danlos Syndrome
Loeys-Dietz syndrome
Aneurysm
Genetic
aortic
thoracic
mutation
dissection
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2011-03-24
Enrollment: 3706
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The cohort consists of patients with conditions related to genetically-induced thoracic aortic aneurysms.

Brief summary: The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) was initiated in 2006 by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). GenTAC established a registry of 3706 patients with genetic conditions that may be related to thoracic aortic aneurysms and collected medical data and biologic samples. The study ended in September 2016. Data and samples are available from NHLBI and requests should be made to BioLINCC. See the NHLBI website for more information: https://www.nhlbi.nih.gov/research/resources/gentac/.


Eligibility criteria: Eligible subjects must have one of the conditions listed below and be enrolled in-person at one of the participating clinical centers.Contact the study coordinator at the location nearest you for more information about participation.

* Marfan syndrome
* Turner syndrome
* Ehlers-Danlos syndrome
* Loeys-Dietz syndrome
* FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 genetic mutation
* Bicuspid aortic valve without known family history
* Bicuspid aortic valve with family history
* Bicuspid aortic valve with coarctation
* Familial Thoracic Aortic Aneurysm and DissectionsYes
* Shprintzen-Goldberg syndrome
* Other aneurysms and dissections of the thoracic aorta not due to trauma, \<50yo
* Other congenital heart disease (e.g., Tetralogy of Fallot, coarctation)

Exclusion Criteria:

* Inability of the patient, parent or guardian to give consent.
* Unwillingness to provide a blood or buccal specimen.

Primary outcomes:
measure: Thoracic aortic aneurysms and dissections and their associated surgical interventions
timeFrame: bi-annual
Secondary outcomes:
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Queens Medical Center
state: Hawaii
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: New York
country: United States
facility: The New York Presbyterian Hospital-Weill Cornell Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas Medical School at Houston
state: Texas
Study officials:
affiliation: RTI International
name: Barbara Kroner, PhD, MPH
role: STUDY_DIRECTOR
affiliation: The New York Presbyterian Hospital-Weill Cornell Medical Center
name: Richard Devereux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: William Ravekes, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Reed E. Pyeritz, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Medical School at Houston
name: Dianna M. Milewicz, M.D. Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Scott A. LeMaire, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: Cheryl L. Maslen, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Hawaii
name: Ralph Shohet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Jennifer Habashi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MedStar Health
name: Federico M. Asch, MD,FACC,FASE
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Kim Eagle, M.D.
role: STUDY_CHAIR
References:
citation: Eagle KA; GenTAC Consortium. Rationale and design of the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). Am Heart J. 2009 Feb;157(2):319-26. doi: 10.1016/j.ahj.2008.10.005. Epub 2008 Dec 17.
citation: Matt P, Schoenhoff F, Habashi J, Holm T, Van Erp C, Loch D, Carlson OD, Griswold BF, Fu Q, De Backer J, Loeys B, Huso DL, McDonnell NB, Van Eyk JE, Dietz HC; GenTAC Consortium. Circulating transforming growth factor-beta in Marfan syndrome. Circulation. 2009 Aug 11;120(6):526-32. doi: 10.1161/CIRCULATIONAHA.108.841981. Epub 2009 Jul 27.
citation: Kuang SQ, Guo DC, Prakash SK, McDonald ML, Johnson RJ, Wang M, Regalado ES, Russell L, Cao JM, Kwartler C, Fraivillig K, Coselli JS, Safi HJ, Estrera AL, Leal SM, LeMaire SA, Belmont JW, Milewicz DM; GenTAC Investigators. Recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections. PLoS Genet. 2011 Jun;7(6):e1002118. doi: 10.1371/journal.pgen.1002118. Epub 2011 Jun 16.
citation: Mendoza DD, Kochar M, Devereux RB, Basson CT, Min JK, Holmes K, Dietz HC, Milewicz DM, LeMaire SA, Pyeritz RE, Bavaria JE, Maslen CL, Song H, Kroner BL, Eagle KA, Weinsaft JW; GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Study Investigators. Impact of image analysis methodology on diagnostic and surgical classification of patients with thoracic aortic aneurysms. Ann Thorac Surg. 2011 Sep;92(3):904-12. doi: 10.1016/j.athoracsur.2011.03.130. Epub 2011 Jul 2.
citation: LeMaire SA, McDonald ML, Guo DC, Russell L, Miller CC 3rd, Johnson RJ, Bekheirnia MR, Franco LM, Nguyen M, Pyeritz RE, Bavaria JE, Devereux R, Maslen C, Holmes KW, Eagle K, Body SC, Seidman C, Seidman JG, Isselbacher EM, Bray M, Coselli JS, Estrera AL, Safi HJ, Belmont JW, Leal SM, Milewicz DM. Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet. 2011 Sep 11;43(10):996-1000. doi: 10.1038/ng.934.
citation: Guo DC, Regalado E, Casteel DE, Santos-Cortez RL, Gong L, Kim JJ, Dyack S, Horne SG, Chang G, Jondeau G, Boileau C, Coselli JS, Li Z, Leal SM, Shendure J, Rieder MJ, Bamshad MJ, Nickerson DA; GenTAC Registry Consortium; National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project; Kim C, Milewicz DM. Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. Am J Hum Genet. 2013 Aug 8;93(2):398-404. doi: 10.1016/j.ajhg.2013.06.019. Epub 2013 Aug 1.
citation: Prakash S, Guo D, Maslen CL, Silberbach M, Milewicz D, Bondy CA; GenTAC Investigators. Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome. Genet Med. 2014 Jan;16(1):53-9. doi: 10.1038/gim.2013.77. Epub 2013 Jun 6.
citation: Cook JR, Carta L, Benard L, Chemaly ER, Chiu E, Rao SK, Hampton TG, Yurchenco P; GenTAC Registry Consortium; Costa KD, Hajjar RJ, Ramirez F. Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome. J Clin Invest. 2014 Mar;124(3):1329-39. doi: 10.1172/JCI71059. Epub 2014 Feb 17.
citation: Song HK, Preiss LR, Maslen CL, Kroner B, Devereux RB, Roman MJ, Holmes KW, Tolunay HE, Desvigne-Nickens P, Asch FM, Milewski RK, Bavaria J, LeMaire SA; GenTAC Consortium. Valve-sparing aortic root replacement in patients with Marfan syndrome enrolled in the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions. J Heart Valve Dis. 2014 May;23(3):292-8.
citation: Doyle JJ, Doyle AJ, Wilson NK, Habashi JP, Bedja D, Whitworth RE, Lindsay ME, Schoenhoff F, Myers L, Huso N, Bachir S, Squires O, Rusholme B, Ehsan H, Huso D, Thomas CJ, Caulfield MJ, Van Eyk JE, Judge DP, Dietz HC; GenTAC Registry Consortium; MIBAVA Leducq Consortium. A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome. Elife. 2015 Oct 27;4:e08648. doi: 10.7554/eLife.08648.
citation: Asch FM, Yuriditsky E, Prakash SK, Roman MJ, Weinsaft JW, Weissman G, Weigold WG, Morris SA, Ravekes WJ, Holmes KW, Silberbach M, Milewski RK, Kroner BL, Whitworth R, Eagle KA, Devereux RB, Weissman NJ; GenTAC Investigators. The Need for Standardized Methods for Measuring the Aorta: Multimodality Core Lab Experience From the GenTAC Registry. JACC Cardiovasc Imaging. 2016 Mar;9(3):219-26. doi: 10.1016/j.jcmg.2015.06.023. Epub 2016 Feb 17.
citation: Guo DC, Gong L, Regalado ES, Santos-Cortez RL, Zhao R, Cai B, Veeraraghavan S, Prakash SK, Johnson RJ, Muilenburg A, Willing M, Jondeau G, Boileau C, Pannu H, Moran R, Debacker J; GenTAC Investigators, National Heart, Lung, and Blood Institute Go Exome Sequencing Project; Montalcino Aortic Consortium; Bamshad MJ, Shendure J, Nickerson DA, Leal SM, Raman CS, Swindell EC, Milewicz DM. MAT2A mutations predispose individuals to thoracic aortic aneurysms. Am J Hum Genet. 2015 Jan 8;96(1):170-7. doi: 10.1016/j.ajhg.2014.11.015. Epub 2014 Dec 31.
citation: Kuang SQ, Medina-Martinez O, Guo DC, Gong L, Regalado ES, Reynolds CL, Boileau C, Jondeau G, Prakash SK, Kwartler CS, Zhu LY, Peters AM, Duan XY, Bamshad MJ, Shendure J, Nickerson DA, Santos-Cortez RL, Dong X, Leal SM, Majesky MW, Swindell EC, Jamrich M, Milewicz DM. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Invest. 2016 Mar 1;126(3):948-61. doi: 10.1172/JCI83778. Epub 2016 Feb 8.
citation: Prakash S, Kuang SQ; GenTAC Registry Investigators; Regalado E, Guo D, Milewicz D. Recurrent Rare Genomic Copy Number Variants and Bicuspid Aortic Valve Are Enriched in Early Onset Thoracic Aortic Aneurysms and Dissections. PLoS One. 2016 Apr 19;11(4):e0153543. doi: 10.1371/journal.pone.0153543. eCollection 2016.
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citation: Prakash SK, Bondy CA, Maslen CL, Silberbach M, Lin AE, Perrone L, Limongelli G, Michelena HI, Bossone E, Citro R; BAVCon Investigators, GenTAC Registry Investigators; Lemaire SA, Body SC, Milewicz DM. Autosomal and X chromosome structural variants are associated with congenital heart defects in Turner syndrome: The NHLBI GenTAC registry. Am J Med Genet A. 2016 Dec;170(12):3157-3164. doi: 10.1002/ajmg.a.37953. Epub 2016 Sep 8.
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