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Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Laval University
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Canada
Information provided by (Responsible Party):
Philippe Pibarot, Laval University
ClinicalTrials.gov Identifier:
NCT01679431
First received: August 24, 2012
Last updated: April 12, 2013
Last verified: April 2013

August 24, 2012
April 12, 2013
April 2005
January 2017   (final data collection date for primary outcome measure)
Progression of aortic valve stenosis [ Time Frame: Patients will be followed every 1 year, up to 5 years ] [ Designated as safety issue: No ]
Annualized progression rate of aortic stenosis hemodynamic severity calculate as the difference between peak aortic jet velocity, transvalvular gradients, and aortic valve area measured at baseline and those measured at the last follow-up divided by the time between the first and last examinations.
Same as current
Complete list of historical versions of study NCT01679431 on ClinicalTrials.gov Archive Site
  • Progression of aortic valve calcification [ Time Frame: Patients will be followed every 2 years, up to 5 years ] [ Designated as safety issue: No ]
    Annualized progression rate of aortic valve calcium
  • Progression of myocardial fibrosis and dysfunction [ Time Frame: PPatients will be followed every 2 years, up to 5 years ] [ Designated as safety issue: No ]
    Annualized progression rate of myocardial fibrosis and global longitudinal myocardial strain
Same as current
  • Progression of aortic calcification and stiffness [ Time Frame: Patients will be followed every 2 years, up to 5 years ] [ Designated as safety issue: No ]
    Annualized progression rate of calcification measured by computed tomography and aortic compliance measured (CT) by cardiac magnetic resonance (CMR) and Doppler-echocardiography
  • Progression of coronary artery calcification [ Time Frame: Patients will be followed every 2 years, up to 5 years ] [ Designated as safety issue: No ]
    Annualized progression rate of coronary artery calcification measured by CT
  • Progression of global hemodynamic load [ Time Frame: Patients will be followed every 1 year, up to 5 years ] [ Designated as safety issue: No ]
    Annualized progression rate of valvulo-arterial impedance measured by Doppler-echocardiography
  • Aortic stenosis related events [ Time Frame: From date of baseline until the date of first documented aortic stenosis related events (as defined on description box), assessed up to 5 years ] [ Designated as safety issue: No ]
    Cardiovascular-related mortality; hospitalization for heart failure; surgical or transcatheter aortic valve replacement motivated by the development of symptoms or LV systolic dysfunction
  • Ischemic cardiovascular events [ Time Frame: From date of baseline until the date of first documented ischemic cardiovascular events (as defined on description box), assessed up to 5 years ] [ Designated as safety issue: No ]
    Myocardial infarction; unstable angina; revascularization procedure
  • All-cause mortality [ Time Frame: From date of baseline until the date of death from any cause assessed up to 5 years ] [ Designated as safety issue: No ]
    Death from any cause
Same as current
 
Metabolic Determinants of the Progression of Aortic Stenosis
Metabolic Determinants of the Progression of Aortic Stenosis - PROGRESSA Study

Calcific aortic stenosis (AS) has become the most common cardiac disease after coronary artery disease and hypertension. Unfortunately no medical therapies have been proven to decrease either the progression of valve stenosis or the resulting adverse effects on myocardial remodeling and function. In light of the studies performed in PROGRESSA, it becomes obvious that: i) AS is a complex and actively regulated process that involves the interaction of several pathways including lipid infiltration and retention, chronic inflammation, osteogenic activation, and active mineralization within the valvular tissues; ii) AS is not a disease strictly limited to the aortic valve but rather a systemic disease that often involves calcification and stiffening of the aorta and impairment of LV function as a consequence of pressure overload. Our findings suggest that the dysmetabolic milieu linked to visceral obesity may accelerate the deterioration of the structure and function not only of the aortic valve but also of the aorta and of the left ventricle. These findings open new avenues of research and provide strong impetus for the elaboration of prospective studies focusing on the "valvulo-metabolic risk" in AS.

The general hypotheses are: The metabolic abnormalities linked to visceral obesity accelerate (1) the progression of valvular calcification and stenosis, aortic calcification and stiffness; (2) the progression of myocardial fibrosis and dysfunction.

The general objectives of the study are to elucidate the mechanisms implicated in the pathogenesis of AS and to identify the metabolic factors that determine the progression of: i) aortic valve calcification and stenosis; ii) myocardial fibrosis and dysfunction; and iii) clinical outcomes.

This study will contribute to identifying the key metabolic determinants of AS progression and will pave the way for the future development of non surgical therapies for this disease. The results of this study would provide strong support to the realization of randomized trial to test the efficacy of lifestyle modification program or new pharmacological treatment aiming at the reduction of visceral fat and associated metabolic abnormalities in the AS population. Furthermore, this study will contribute to the identification of novel blood and imaging biomarkers of faster disease progression, which will help to optimize risk stratification and timing of AVR in the AS population.

Not Provided
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Fasting blood sample (serum, lithium-heparin, EDTA) and white cells - Tissue (explanted aortic valves)

Probability Sample

Cohort will be selected at primary care clinic

Aortic Valve Stenosis
  • Other: Doppler-echocardiography
  • Radiation: Computed tomography
  • Other: Magnetic resonance imaging
  • Biological: Fasting blood sample
Patients with aortic stenosis

Patients have every year: 1) an assessment of cardiometabolic risk profile with measure of body mass index, waist circumference and fasting blood sample and 2) a comprehensive Doppler-echocardiographic exam.

Computed tomography and magnetic resonance imaging are performed every 2 years.

Interventions:
  • Other: Doppler-echocardiography
  • Radiation: Computed tomography
  • Other: Magnetic resonance imaging
  • Biological: Fasting blood sample

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
250
Not Provided
January 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age >21 years
  • Presence of aortic stenosis defined as peak aortic jet velocity ≥2.5 m/s

Exclusion Criteria:

  • Symptomatic aortic stenosis
  • Very severe aortic stenosis defined as an AVA≤0.6 cm2
  • Left ventricular ejection fraction < 50%
  • More than mild aortic or mitral regurgitation, or mitral stenosis
  • Atrial fibrillation or flutter
  • Pregnant or lactating women
  • Contraindications to gadolinium-enhanced MRI
Both
21 Years and older
Yes
Contact: Philippe Pibarot, PhD, DVM 418-656-8711 ext 5938 Philippe.Pibarot@med.ulaval.ca
Contact: Romain Capoulade, MSc 418-656-8711 ext 3845 Romain.Capoulade@criucpq.ulaval.ca
Canada
 
NCT01679431
MOP-114997
No
Philippe Pibarot, Laval University
Laval University
  • Canadian Institutes of Health Research (CIHR)
  • Heart and Stroke Foundation of Canada
Principal Investigator: Philippe Pibarot, PhD, DVM Institut Universitaire de Cardiologie et de Pneumologie de Québec
Laval University
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP