Genetic of Aortic Valve Stenosis - Clinical and Therapeutic Implications (GENERAC)

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ClinicalTrials.gov Identifier: NCT00647088

Recruitment Status : Unknown

Verified February 2016 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was: Recruiting

First Posted : March 31, 2008

Last Update Posted : March 1, 2017

Sponsor:

Collaborator:

Institut National de la Santé Et de la Recherche Médicale, France

Information provided by (Responsible Party):

Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

Pathophysiology of Aortic Valve Stenosis remains poorly known. The aim of the present study is to identify genetic factors involved in this disease using a case control trial design.

Condition or disease
Aortic Valve Stenosis

Detailed Description:

Aortic valve stenosis (AS) is the most common valvular disease and the second most common indication for cardiac surgery in Western countries. AS has long been considered as a passive and degenerative process. Recent data challenged this concept, showing that AS is an active and highly regulated process with some similarities to atherosclerosis. However, pathophysiology of AS remains poorly understood and preliminary data suggest that genetic factors may be involved. The aim of the present study is to identify genetic factors involved in this disease using a case control trial design (1000 patients with AS and 1500 controls with no evidence of valve disease). For all patients and controls, blood samples including DNA and echocardiography will be performed.

Study Design

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Study Type :	Observational
Estimated Enrollment :	2200 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	Genetic of Aortic Valve Stenosis - Clinical and Therapeutic Implications
Study Start Date :	March 2008
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	December 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Supravalvular aortic stenosis

Genetic and Rare Diseases Information Center resources: Aortic Valve Stenosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
aortic stenosis various age and disease severity
Controls Controls free of valvular disease

Outcome Measures

Primary Outcome Measures :

Identification of genetic polymorphisms of fetuin-A, matrix-GLA protein, vitamin D receptor [ Time Frame: end of the study ]

Secondary Outcome Measures :

Identification of other genetic polymorphisms [ Time Frame: End of the Study ]

Biospecimen Retention: Samples With DNA

blood samples DNA Tissue valve

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

case control study Case = patients with aortic valve stenosis Controls = participants free of aortic valve stenosis

Criteria

Patients:

Inclusion criteria :

Age >=18 years
Pure isolated degenerative aortic valve stenosis

Exclusion criteria :

Rheumatic, congenital or post-radiation aortic stenosis
Severe renal insufficiency (clearance < 30 ml/min)
Aortic insufficiency > or = grade 2/4
Other valve disease > or = grade 2/4

Controls

Inclusion criteria :

- Age >=18 years

Exclusion criteria :

Known first degree relative with aortic valve stenosis
Severe renal insufficiency (clearance < 30 ml/min)
Any valve disease > or = grade 2/4

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00647088

Locations

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France
Assistance Publique - Hôpitaux de Paris, Bichat Hospital	Recruiting
Paris, France, 75018
Contact: David MESSIKA-ZEITOUN, MD 01 40 25 66 01 ext 00 33 david.messika-zeitoun@bch.aphp.fr
Principal Investigator: David Messika-Zeitoun

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

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Principal Investigator:	David Messika-Zeitoun, MD	Assistance Publique - Hôpitaux de Paris

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Perrot N, Thériault S, Dina C, Chen HY, Boekholdt SM, Rigade S, Després AA, Poulin A, Capoulade R, Le Tourneau T, Messika-Zeitoun D, Trottier M, Tessier M, Guimond J, Nadeau M, Engert JC, Khaw KT, Wareham NJ, Dweck MR, Mathieu P, Pibarot P, Schott JJ, Thanassoulis G, Clavel MA, Bossé Y, Arsenault BJ. Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification. JAMA Cardiol. 2019 Jul 1;4(7):620-627. doi: 10.1001/jamacardio.2019.1581. Erratum in: JAMA Cardiol. 2019 Jul 1;4(7):714.

Pawade T, Clavel MA, Tribouilloy C, Dreyfus J, Mathieu T, Tastet L, Renard C, Gun M, Jenkins WSA, Macron L, Sechrist JW, Lacomis JM, Nguyen V, Galian Gay L, Cuéllar Calabria H, Ntalas I, Cartlidge TRG, Prendergast B, Rajani R, Evangelista A, Cavalcante JL, Newby DE, Pibarot P, Messika Zeitoun D, Dweck MR. Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis. Circ Cardiovasc Imaging. 2018 Mar;11(3):e007146. doi: 10.1161/CIRCIMAGING.117.007146.

Kubota N, David Messika-Zeitoun D. P650Influence of fetunin-a level on progression of calcific aortic valve stenosis The COFRASA - GENERAC Study. Eur Heart J Cardiovasc Imaging. 2016 Dec 1;17(suppl_2):ii130-ii136. doi: 10.1093/ehjci/jew250.001.

Arangalage D, Nguyen V, Robert T, Melissopoulou M, Mathieu T, Estellat C, Codogno I, Huart V, Duval X, Cimadevilla C, Vahanian A, Dehoux M, Messika-Zeitoun D. Determinants and prognostic value of Galectin-3 in patients with aortic valve stenosis. Heart. 2016 Jun 1;102(11):862-8. doi: 10.1136/heartjnl-2015-308873. Epub 2016 Feb 19.

Guauque-Olarte S, Messika-Zeitoun D, Droit A, Lamontagne M, Tremblay-Marchand J, Lavoie-Charland E, Gaudreault N, Arsenault BJ, Dubé MP, Tardif JC, Body SC, Seidman JG, Boileau C, Mathieu P, Pibarot P, Bossé Y. Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease. Circ Cardiovasc Genet. 2015 Dec;8(6):812-22. doi: 10.1161/CIRCGENETICS.115.001145. Epub 2015 Nov 9.

Chin CW, Messika-Zeitoun D, Shah AS, Lefevre G, Bailleul S, Yeung EN, Koo M, Mirsadraee S, Mathieu T, Semple SI, Mills NL, Vahanian A, Newby DE, Dweck MR. A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis. Eur Heart J. 2016 Feb 21;37(8):713-23. doi: 10.1093/eurheartj/ehv525. Epub 2015 Oct 21.

Dreyfus J, Durand-Viel G, Raffoul R, Alkhoder S, Hvass U, Radu C, Al-Attar N, Ghodbhane W, Attias D, Nataf P, Vahanian A, Messika-Zeitoun D. Comparison of 2-Dimensional, 3-Dimensional, and Surgical Measurements of the Tricuspid Annulus Size: Clinical Implications. Circ Cardiovasc Imaging. 2015 Jul;8(7):e003241. doi: 10.1161/CIRCIMAGING.114.003241.

Nguyen V, Cimadevilla C, Estellat C, Codogno I, Huart V, Benessiano J, Duval X, Pibarot P, Clavel MA, Enriquez-Sarano M, Vahanian A, Messika-Zeitoun D. Haemodynamic and anatomic progression of aortic stenosis. Heart. 2015 Jun;101(12):943-7. doi: 10.1136/heartjnl-2014-307154. Epub 2015 Feb 5.

Kochtebane N, Passefort S, Choqueux C, Ainoun F, Achour L, Michel JB, Bäck M, Jacob MP. Release of leukotriene B4, transforming growth factor-beta1 and microparticles in relation to aortic valve calcification. J Heart Valve Dis. 2013 Nov;22(6):782-8.

Cimadevilla C, Cueff C, Hekimian G, Dehoux M, Lepage L, Iung B, Duval X, Huart V, Tubach F, Vahanian A, Messika-Zeitoun D. Prognostic value of B-type natriuretic peptide in elderly patients with aortic valve stenosis: the COFRASA-GENERAC study. Heart. 2013 Apr;99(7):461-7. doi: 10.1136/heartjnl-2012-303284. Epub 2013 Jan 24.

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Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00647088
Other Study ID Numbers:	P070141
First Posted:	March 31, 2008 Key Record Dates
Last Update Posted:	March 1, 2017
Last Verified:	February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Aortic Valve stenosis Genetic Mineralisation inhibitors

Additional relevant MeSH terms:

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Aortic Valve Stenosis Constriction, Pathologic Pathological Conditions, Anatomical Aortic Valve Disease	Heart Valve Diseases Heart Diseases Cardiovascular Diseases Ventricular Outflow Obstruction

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