A Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification

Phase 2

Completed

Conditions: Aortic Valve Stenosis

Interventions: Drug: Ataciguat (HMR1766)

Registration Number: NCT02481258

Lead Sponsor: Mayo Clinic

Brief Summary: The primary objective of the current study is to determine whether Ataciguat (HMR1766) slows progression of valve calcification in patients with moderate calcific aortic valve stenosis. Secondary and tertiary objectives are to determine whether Ataciguat slows progression of aortic valve function, reduces systemic inflammation, and prevents left ventricular dysfunction in patients with moderate calcific aortic valve stenosis.

Detailed Description: Patients with Moderate Calcific Aortic Valve Stenosis may be eligible for enrollment in this study. Participation lasts 12 months, which includes a total of 3 study visits (baseline/screening visit, 6 month follow up visit and 12 month follow up visit). During each visit, a blood sample will be taken along with other research related tests (Orthostatic Tolerance Standing Test, CT Scan, Echocardiogram, DEXA Scan). Qualifying Participants will be supplied with 6 months worth of study medication or placebo during visits 1 (baseline/screening visit) and 2 (6 month follow up visit) in which they will take at home daily with food. On visit 3 (12 month follow up visit), any remaining study medication or placebo will be returned to study staff.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ataciguat (HMR1766)	Ataciguat (HMR1766)	200mg taken daily for 12 months

Primary Outcome Measures

Name	Time	Method
Changes in Aortic Valve Calcium Levels	baseline, 6 mos	This will be done using computed tomography (CT) scanning to evaluate aortic valve calcium levels, which is considered to be a "gold standard" for evaluating valvular calcium burden. As measured in Arbitrary Units (AU).

Secondary Outcome Measures

Name	Time	Method
Change in Levels of Plasma Interleukin-6	baseline, 6 mos	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling and reduce levels of circulating inflammatory cytokines in patients with mild to moderate CAVS. This will be done using ELISA-based measurements of interleukin-6 and tumor necrosis factor alpha in venous blood samples. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in inflammatory cytokine levels from baseline in subjects receiving HMR1766 or placebo capsules.
Change in Aortic Valve Function: Aortic Valve Area	baseline, 6 mos	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and 2. mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.
Change in Plasma Tumor Necrosis Factor Alpha	Baseline, 6 months	Determine whether long-term treatment with ataciguat reduces levels of circulating inflammatory cytokines.
Change in Aortic Valve Function: Transvalvular Pressure Gradient	baseline, 6 mos	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and 2. mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.
Change in Left Ventricular Function	baseline, 6 mos	Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. Left ventricular systolic function (measured by echocardiographic measurement of left ventricular ejection fraction) and 2. Left ventricular diastolic function (measured using the E/A ratio derived from Doppler measurements).