Clinical trial NCT02481258: A Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification
Official title: A Phase II Randomized, Placebo-Controlled, Double-Blinded Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification in Patients With Moderate Calcific Aortic Valve Stenosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aortic Valve Stenosis
Keywords: Stenosis
Aortic Valve
Aorta
Calcified
Calcific
Calcification
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Sanofi
name: National Institutes of Health (NIH)
First posted: 2015-06-25
Enrollment: 35
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

1. Age \> 50 years
2. Male or female sex
3. Aortic valve area greater than 1.0 cm2 but less than 2.0 cm2
4. Aortic valve calcium levels greater than 300 AU from chest CT
5. Ejection fraction \>50%

Exclusion Criteria

1. Orthostatic intolerance or symptomatic hypotension prior to study or during study visits
2. Positive pregnancy test during screening visit
3. Nitrate use or α-antagonist medication use within 24 hours
4. Systolic blood pressure \<110 mm Hg
5. Mean systemic arterial pressure \<75 mm Hg
6. Severe mitral or aortic regurgitation
7. Retinal or optic nerve problems
8. Recent (≤30 days) acute coronary syndrome
9. Oxygen saturation \<90% on room air
10. Congenital valve disease
11. Hepatic dysfunction/elevated liver enzymes
12. Prescription of drugs known to alter NO-sGC-cGMP signaling (sildenafil, nitrates, etc.)
13. Prescription of Warfarin (Coumadin) for chronic anticoagulation
14. Concomitant participation in other trials at Mayo Clinic or elsewhere
15. Use of phenytoin or related compounds for any indication
16. Chronic midazolam treatment for any indication
17. Use of monoamine oxidase inhibitors for any indication
18. Use of anti-diabetic drugs in the sulfonylurea family

Primary outcomes:
measure: Changes in Aortic Valve Calcium Levels
timeFrame: baseline, 6 mos
Secondary outcomes:
measure: Change in Levels of Plasma Interleukin-6
timeFrame: baseline, 6 mos
measure: Change in Aortic Valve Function: Aortic Valve Area
timeFrame: baseline, 6 mos
measure: Change in Left Ventricular Function
timeFrame: baseline, 6 mos
measure: Change in Plasma Tumor Necrosis Factor Alpha
timeFrame: Baseline, 6 months
measure: Change in Aortic Valve Function: Transvalvular Pressure Gradient
timeFrame: baseline, 6 mos
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Jordan D Miller, PhD
role: PRINCIPAL_INVESTIGATOR
References: