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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01961453
Recruitment Status : Withdrawn (Funding)
First Posted : October 11, 2013
Last Update Posted : August 11, 2016
Information provided by (Responsible Party):
Corporal Michael J. Crescenz VA Medical Center

Brief Summary:
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 or disease Intervention/treatment Phase
Hypertension Drug: Isosorbide Mononitrate, sustained release Drug: Placebo capsule Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Targeting Wave Reflections to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function in Hypertension
Study Start Date : August 2013
Actual Primary Completion Date : January 2016
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Change in left ventricular mass [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. Change in extracellular volume fraction [ Time Frame: 24 weeks ]
  2. Change in peak myocardial systolic longitudinal strain measured by MRI [ Time Frame: 24 weeks ]
  3. Change in peak early diastolic intraventricular pressure gradient measured by MRI [ Time Frame: 24 weeks ]
  4. Change in late systolic hypertension derived from pulse wave analysis [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01961453

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

Responsible Party: Corporal Michael J. Crescenz VA Medical Center Identifier: NCT01961453     History of Changes
Other Study ID Numbers: 01442
First Posted: October 11, 2013    Key Record Dates
Last Update Posted: August 11, 2016
Last Verified: October 2014

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

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