Trial record 8 of 1390 for:    "Mayo Clinic" [Exact]

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2015 by Mayo Clinic
Sponsor:
Collaborators:
Sanofi
Information provided by (Responsible Party):
Jordan D. Miller, Ph.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02481258
First received: June 23, 2015
Last updated: NA
Last verified: June 2015
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Aortic Valve Stenosis
Drug: Ataciguat (HMR1766)
Other: Placebo Comparator: Matching Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Changes in aortic valve calcium levels measured by computed tomography scanning every 6 months of treatment during the trial [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling and halt accumulation of aortic valve calcium in patients with mild to moderate CAVS. This will be done using computed tomography (CT) scanning. Key comparision will be differences in the rate of change of calcium between patients receiving HMR1766 or placebo capsules.


Secondary Outcome Measures:
  • Change in levels of plasma interleukin-6 and plasma tumor necrosis factor alpha following 6 and 12 months of treatment [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    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 following 6 and 12 months of treatment [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

    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 following 6 and 12 months of treatment [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 100
Study Start Date: June 2015
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ataciguat (HMR1766)
200mg taken daily for 12 months
Drug: Ataciguat (HMR1766)
Placebo Comparator: Matching Placebo
Taken Daily for 12 months
Other: Placebo Comparator: Matching Placebo

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

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT02481258

Contacts
Contact: Brandon J Dunagan, AAS/AS 507-255-7566 Dunagan.Brandon@mayo.edu

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Sanofi
Investigators
Principal Investigator: Jordan D Miller, PhD Mayo Clinic
  More Information

No publications provided

Responsible Party: Jordan D. Miller, Ph.D., SAC II, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02481258     History of Changes
Other Study ID Numbers: 14-006469, TR 000954
Study First Received: June 23, 2015
Last Updated: June 23, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Stenosis
Aortic Valve
Aorta
Calcified
Calcific
Calcification

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

ClinicalTrials.gov processed this record on August 02, 2015