NCT04312139

Brief Summary

AthenaValve aims to develop and initial validate a novel serum diagnostic kit, for the assessment of severity and prognosis of progression of aortic valve stenosis (AS, a devastating disease without early diagnosis and medical treatment). Two independent clinical cohorts of patients will provide serum samples, along with tissue and serum of a validated animal model of the disease for evaluation of the early stages, in order to develop and validate a multiplexed Enzyme-linked Immunosorbent Assay kit (multiplex ELISA). Advanced bioinformatics analysis will facilitate the selection of the most promising molecules from integrated proteomics-transcriptomics-metabolomics data. The novel biomarkers will help clinicians to early diagnose patients at high risk and will pave the way for the experimental implementation of promising pharmaceutical therapies. Moreover, AthenaValve aims to shed light on the systemic cellular interplay of the same patients, by analyzing the circulating immune cell phenotypes of the subgroups of rapid and slow progression patients

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
280

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2020

Longer than P75 for all trials

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2020

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

March 14, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 18, 2020

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2025

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2025

Completed
Last Updated

October 4, 2022

Status Verified

October 1, 2022

Enrollment Period

5 years

First QC Date

March 14, 2020

Last Update Submit

October 1, 2022

Conditions

Calcific Aortic Valve DiseaseAortic Valve StenosisAortic Valve, Calcification of

Keywords

aortic valve stenosiscalcific aortic valve diseaseaortic stenosisbiomineralizationcalcificationcardiovascular calcificationserum diagnosticsmultiplex ELISALC-MS/MSbioinformaticsdisease progressionIntegrated proteomics-metabolomics-transcriptomicsMass cytometryFlow cytometryImmune cells

Outcome Measures

Primary Outcomes (2)

  • multiplex ELISA kit Sensitivity

    Overall multiplex ELISA kit sensitivity for the detection of fast aortic valve stenosis progression (dVmax\>0.25 m/sec/year)

    5 years

  • multiplex ELISA kit Specificity

    Overall multiplex ELISA kit specificity for the detection of fast aortic valve stenosis progression (dVmax\>0.25 m/sec/year)

    5 years

Secondary Outcomes (4)

  • Fast progressors percentage

    5 years

  • Severe AS percentage

    5 years

  • Coronary Artery Disease progression percentage

    5 years

  • Major Adverse Cardiovascular Events rate

    5 years

Other Outcomes (1)

  • Differential PBMC profile

    5 years

Study Arms (4)

Fast progressors of Aortic Valve Stenosis

50 patients that retrospectively demonstrated fast progression from moderate to severe aortic valve stenosis: echocardiographic dVmax\>0.25 m/sec/year (difference in transaortic Vmax).

Other: Untargeted LC/MS and LC-MS/MS

Slow progressors of Aortic Valve Stenosis

50 patients that retrospectively demonstrated slow progression from moderate to severe aortic valve stenosis: echocardiographic dVmax\<0.15 m/sec/year (difference in transaortic Vmax).

Other: Untargeted LC/MS and LC-MS/MS

Prospective Moderate Aortic Valve Stenosis

100 consecutive prospectively enrolled patients with moderate aortic valve stenosis. Plus 20 patients accounting for 20% drop-out rate, total prospective cohort = 120 patients.

Diagnostic Test: EchocardiographyDiagnostic Test: Computerized Tomography Aortic Valve Calcium ScoreOther: Targeted LC/MS and LC-MS/MSDiagnostic Test: multiplex ELISA

Negative calcium score group

50 patients at intermediate to high risk for Cardiovascular Disease (CVD) and negative aortic valve and coronary calcium score at CT scan, prospectively followed-up. Plus 10 patients accounting for 20% drop-out rate, total control cohort = 60 patients.

Diagnostic Test: EchocardiographyDiagnostic Test: Computerized Tomography Aortic Valve Calcium ScoreOther: Targeted LC/MS and LC-MS/MSDiagnostic Test: multiplex ELISA

Interventions

EchocardiographyDIAGNOSTIC_TEST

Baseline and prospective follow-up echocardiography

Negative calcium score groupProspective Moderate Aortic Valve Stenosis
Computerized Tomography Aortic Valve Calcium ScoreDIAGNOSTIC_TEST

Baseline and prospective follow-up CT calcium score of aortic valve

Negative calcium score groupProspective Moderate Aortic Valve Stenosis
Untargeted LC/MS and LC-MS/MSOTHER

Serum samples untargeted proteomics and metabolomics

Fast progressors of Aortic Valve StenosisSlow progressors of Aortic Valve Stenosis
Targeted LC/MS and LC-MS/MSOTHER

Serum samples targeted proteomics and metabolomics

Negative calcium score groupProspective Moderate Aortic Valve Stenosis
multiplex ELISADIAGNOSTIC_TEST

Implementation of novel multiplex ELISA assay on serum samples of aortic valve stenosis prospective cohort.

Negative calcium score groupProspective Moderate Aortic Valve Stenosis

Eligibility Criteria

Age60 Years - 87 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Patients diagnosed with moderate and severe tricuspid aortic valve stenosis of degenerative etiology.

You may qualify if:

  • Retrospective cohort: patients with severe aortic valve stenosis in echocardiography:
  • Vmax \> 4 m/sec and mean Gradient \>40 mmHg and/or Aortic Valve Area indexed (AVAi) \< 0.6 cm2/m2 and/or Velocity index \<0.25 whichever worse, with available complete past echocardiographic follow-up (\>2 past studies) indicating disease progression, by the same performing physician.
  • Prospective cohort: patients with moderate aortic valve stenosis in echocardiography:
  • Vmax 3-4 m/sec and mean Gradient 25-40 mmHg and/or AVAi 0.6-0.9 cm2/m2,
  • Where inconsistent: Velocity index = 0.25-0.50.
  • Technical details: Optimal doppler measurements obtained by the best feasible echocardiographic window (demonstrating at least 2 windows, where possible including right parasternal with or without pencil probe).
  • Prospective Control group: patients at intermediate to high risk for CVD according to atherosclerotic risk factors assessment - Heart Score

You may not qualify if:

  • Echocardiographic Stroke Volume indexed (SVi) \<35 ml/m2
  • Bicuspid aortic valve
  • Stenosis of rheumatic etiology
  • More than mild aortic valve regurgitation
  • More than mild mitral valve regurgitation
  • More than mild mitral stenosis
  • Severe pulmonary hypertension
  • Chronic ischemic heart failure with Ejection Fraction \< 45%
  • Right heart failure (based on the echocardiographic assessment of Right Ventricle Dimension, Tricuspid Annular Plane Systolic Excursion, tricuspid annular velocity, and clinical syndrome)
  • Acutely decompensated Heart Failure with preserved Ejection Fraction \<4 weeks
  • N-terminal-pro hormone Brain Natriuretic Peptide (NT-proBNP)\> 900 pg/ml for ages 60-75, NT-pro-BNP \> 1800 pg/ml for ages \>75 years
  • Presence of chronic systematic inflammatory disease
  • Presence of autoimmune disease
  • Active malignancy
  • History of chemotherapy past 3 years
  • +38 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

First Department of Cardiology, University of Athens, Medical School. Hippocratio Hospital

Athens, Attica, 11528, Greece

RECRUITING

Naval Hospital of Athens

Athens, Greece

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Serum from peripheral blood

MeSH Terms

Conditions

Aortic Valve StenosisAortic Valve, Calcification ofCalcinosisDisease Progression

Interventions

EchocardiographyLiquid Chromatography-Mass Spectrometry

Condition Hierarchy (Ancestors)

Aortic Valve DiseaseHeart Valve DiseasesHeart DiseasesCardiovascular DiseasesVentricular Outflow ObstructionCalcium Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cardiac Imaging TechniquesDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisUltrasonographyHeart Function TestsDiagnostic Techniques, CardiovascularChromatography, LiquidChromatographyChemistry Techniques, AnalyticalInvestigative TechniquesMass Spectrometry

Study Officials

  • Konstantinos P Toutouzas, Professor

    First Department of Cardiology, Athens Medical School, NKUA

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Nikolaos Anousakis-Vlachochristou, MD

CONTACT

00302132088099anousakisvn@med.uoa.gr

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Cardiology

Study Record Dates

First Submitted

March 14, 2020

First Posted

March 18, 2020

Study Start

March 1, 2020

Primary Completion

March 1, 2025

Study Completion

September 1, 2025

Last Updated

October 4, 2022

Record last verified: 2022-10

Locations

GR(2)