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Effect of Isosorbide Mononitrate on Hypertension to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function (ISMN)

This study has been withdrawn prior to enrollment.
(Funding)
Sponsor:
Information provided by (Responsible Party):
Corporal Michael J. Crescenz VA Medical Center
ClinicalTrials.gov Identifier:
NCT01961453
First received: October 9, 2013
Last updated: August 9, 2016
Last verified: October 2014
  Purpose
The purpose of this research study is to test whether treatment with isosorbide mononitrate will improve left ventricular hypertrophy ("thickening") which puts people at risk for developing heart failure. Once it develops, heart failure is a very serious condition and thus it is important to find ways to prevent it from happening. The investigators have reasons to believe that dilating the blood vessels with this specific medication will improve the thickening of the heart, which increases the risk of heart failure.

Condition Intervention Phase
Hypertension
Drug: Isosorbide Mononitrate, sustained release
Drug: Placebo capsule
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Targeting Wave Reflections to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function in Hypertension

Resource links provided by NLM:


Further study details as provided by Corporal Michael J. Crescenz VA Medical Center:

Primary Outcome Measures:
  • Change in left ventricular mass [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in extracellular volume fraction [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in peak myocardial systolic longitudinal strain measured by MRI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in peak early diastolic intraventricular pressure gradient measured by MRI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in late systolic hypertension derived from pulse wave analysis [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: August 2013
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Isosorbide Mononitrate, sustained release
One tablet containing 60 mg (Titration Stage 1) OR 120 mg (Titration Stage 2) of sustained-release ISMN administered at 8 AM.
Drug: Isosorbide Mononitrate, sustained release
60 mg if Titration Stage 1 OR 120 mg if Titration Stage 2
Placebo Comparator: Placebo capsule
One capsule of placebo administered once daily at 8 AM
Drug: Placebo capsule
One capsule of placebo administered once daily at 8 am.

  Eligibility

Ages Eligible for Study:   18 Years to 89 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Systolic blood pressure >140 mmHg, diastolic blood pressure > 90 mmHg.
  • An elevated left ventricular mass index (defined as >60 g/m1.7 in women and 80 g/m1.7 in men) OR LV posterior wall thickness >1.4 cm documented in a clinically indicated echocardiographic examination or magnetic resonance imaging scan within the previous 12 months.
  • Stable medical therapy as defined by: (1)No addition or removal of ACE inhibitors, angiotensin receptor blockers, beta-blockers, or calcium channel blockers for 30 days. (2)No change in dosage of ACE, angiotensin-receptor blocker, beta-blockers or calcium-channel blockers s of more than 100% for 30 days.
  • Current therapy with an ACE inhibitor, hydralazine or a statin, all of which have been shown to reduce nitrate tolerance.

Exclusion Criteria:

  • Rhythm other than sinus rhythm (i.e., atrial fibrillation).
  • Non-cardiac condition limiting life expectancy to less than one year, per physician judgment.
  • Current or anticipated future need for nitrate therapy.
  • Valve disease (> mild aortic or mitral stenosis; > moderate aortic or mitral regurgitation).
  • Hypertrophic cardiomyopathy.
  • Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid).
  • Pericardial disease.
  • Primary pulmonary arteriopathy.
  • Have experienced a myocardial infarction or unstable angina, or have undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days prior to consent, or requires either PTCA or CABG at the time of consent.
  • Resting heart rate (HR) > 100 bpm.
  • A reduced LV ejection fraction (EF<50%).
  • Known severe liver disease (AST > 3x normal, alkaline phosphatase or bilirubin > 2x normal).
  • Patients with a clinically indicated stress test demonstrating significant ischemia within a year of enrollment which was not followed by percutaneous or surgical revascularization.
  • Allergy to isosorbide mononitrate.
  • Current therapy with phosphodiesterase inhibitors, such as sildenafil, vardenafil or tadalafil, since the combination of nitrates and phosphodiesterase inhibitors can result in severe hypotension.
  • Therapy with rosiglitazone, since this combination is not recommended based on epidemiologic data suggesting that it may increase the risk of myocardial ischemia.
  • Current pregnancy or a positive urine pregnancy test. Women who become pregnant during the study will be discontinued from the trial.
  • Contraindications to a cardiac MRI: (i) Central nervous system aneurysm clips; (ii) Implanted neural stimulators; (iii) Implanted cardiac pacemaker or defibrillator; (iv) Cochlear implant; (v) Ocular foreign body (e.g. metal shavings); (vi) Other implanted medical devices: (e.g. drug infusion ports); (vii) Insulin pump; (viii) Metal shrapnel or bullet; (ix) Claustrophobia; (x) Extreme obesity rendering the patient unable to fit into narrow-bore scanners; (xi) Unwillingness of the patient to undergo a cardiac MRI. All patients with metallic implants will be individually evaluated prior to MRI.
  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: NCT01961453

Locations
United States, Pennsylvania
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Corporal Michael J. Crescenz VA Medical Center
Investigators
Principal Investigator: Julio A Chirinos, MD, PhD Philadelphia VA Medical Center & University of Pennsylvania
  More Information

Publications:
Responsible Party: Corporal Michael J. Crescenz VA Medical Center
ClinicalTrials.gov Identifier: NCT01961453     History of Changes
Other Study ID Numbers: 01442 
Study First Received: October 9, 2013
Last Updated: August 9, 2016
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Corporal Michael J. Crescenz VA Medical Center:
Hypertension
Isosorbide Mononitrate
Myocardial fibrosis

Additional relevant MeSH terms:
Hypertension
Fibrosis
Hypertrophy
Hypertrophy, Left Ventricular
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Pathological Conditions, Anatomical
Cardiomegaly
Heart Diseases
Isosorbide
Isosorbide-5-mononitrate
Isosorbide Dinitrate
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Vasodilator Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 28, 2016