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
  Purpose

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.


Condition Intervention
Aortic Valve Stenosis
Other: Doppler-echocardiography
Radiation: Computed tomography
Other: Magnetic resonance imaging
Biological: Fasting blood sample

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Metabolic Determinants of the Progression of Aortic Stenosis - PROGRESSA Study

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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


Biospecimen Retention:   Samples With DNA

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


Estimated Enrollment: 250
Study Start Date: April 2005
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Cohort will be selected at primary care clinic

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01679431

Contacts
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

Locations
Canada, Quebec
Institut Universitaire de Cardiologie et de Pneumologie de Québec Recruiting
Québec, Quebec, Canada, G1V4G5
Contact: Philippe Pibarot, PhD    418-656-8711 ext 5938    Philippe.Pibarot@med.ulaval.ca   
Contact: Romain Capoulade, MSc    418-656-8711 ext 3845    Romain.Capoulade@criucpq.ulaval.ca   
Principal Investigator: Phillipe Pibarot, PhD         
Sponsors and Collaborators
Laval University
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Canada
Investigators
Principal Investigator: Philippe Pibarot, PhD, DVM Institut Universitaire de Cardiologie et de Pneumologie de Québec
  More Information

Publications:

Responsible Party: Philippe Pibarot, Doctor, Laval University
ClinicalTrials.gov Identifier: NCT01679431     History of Changes
Other Study ID Numbers: MOP-114997
Study First Received: August 24, 2012
Last Updated: April 12, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Laval University:
Aortic Stenosis
Obesity, Abdominal
Metabolic Syndrome X
Insulin Resistance
Echocardiography, Doppler
Multidetector Computed Tomography
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Aortic Valve Stenosis
Constriction, Pathologic
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on August 27, 2014