Platelet Adhesion in the Pathobiology of Aortic Stenosis

Aortic Valve Stenosis Clinical Trial

Official title:

Platelet Adhesion in the Pathobiology of Aortic Stenosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05550896
• Other study ID #: HSR220332
• Status: Recruiting
• Start date: January 3, 2023
• Est. completion date: June 1, 2028

Study information

• Verified date: April 2023
• Source: University of Virginia
• Contact: Jonathan Lindner, MD
• Phone: 434 297-9442
• Email: jlindner[@]virginia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Aortic stenosis (AS) is a serious and common condition that affects 2-3% of the population >65 years of age in Western countries. It is also responsible for extraordinarily high healthcare expenditures, estimated to be over $6 billion annually,2 in part because the primary treatment for severe AS is aortic valve replacement (AVR) which is resource-intensive. Valve abnormalities are frequently recognized before AS becomes severe, or before there is need for guideline-directed procedural intervention, thereby providing an opportunity for pharmacologic intervention to slow disease progression. Yet, all attempts to prevent AS progression in those with degenerative non-congenital forms of disease have failed. The only non-procedural intervention that benefits patients with moderate or greater AS is the aggressive treatment of hypertension, which reduces net left ventricular (LV) afterload (valvulo-arterial impedance [Zva]) and can slow secondary LV remodeling. The overall goal of this proposal is to integrate advanced imaging and vascular biology to study how von Willebrand factor (VWF) and platelet adhesion promote AS progression through many parallel pathways, thereby representing a potential therapeutic target. We are hypothesizing that blood markers of abnormal VWF proteolysis and platelet-derived factors, and abnormal valve shear patterns which can be detected by advanced analysis of spectral Doppler on echocardiography are predictors for progressive AS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: June 1, 2028
• Est. primary completion date: August 30, 2027
• Gender: All
• Age group: 25 Years and older

Eligibility

Inclusion Criteria For AS group

• Age >25 years of age

• Mild or moderate calcific, non-congenital aortic stenosis by echocardiography within the prior 3 months defined as:

• aortic valve area 1.0 cm2 - 1.9 cm2 and either

• peak velocity of >2.5 m/s and <4.0 m/s with normal or mildly reduced stroke volume index (>25 ml/m2), or

• VTI ratio (LVOT:AoV) of <0.5 and >0.25 with abnormal stroke volume (<35 ml/m2 or >60 ml/m2).

• Age and sex-matched control subjects undergoing echocardiography with no aortic stenosis, and no more than mild severity disease of other valves.

Inclusion criteria for Control Group

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Diagnostic Test:
• Echocardiogaphy
Assessment of high velocity low amplitude signals on Doppler echocardiography

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ozawa K, Muller MA, Varlamov O, Hagen MW, Packwood W, Morgan TK, Xie A, Lopez CS, Chung D, Chen J, Lopez JA, Lindner JR. Reduced Proteolytic Cleavage of von Willebrand Factor Leads to Aortic Valve Stenosis and Load-Dependent Ventricular Remodeling. JACC Basic Transl Sci. 2022 Jun 29;7(7):642-655. doi: 10.1016/j.jacbts.2022.02.021. eCollection 2022 Jul. Erratum In: JACC Basic Transl Sci. 2023 Feb 27;8(2):237. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evidence for High Shear Patterns on Echocardiography	Low-amplitude high velocity signals on spectral Doppler	4 years
Secondary	Plasma markers of VWF	Plasma markers including VWF antigen, oxidation, cleavage; and ADAMTS13 activity	4 years