- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01961453
Effect of Isosorbide Mononitrate on Hypertension to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function (ISMN)
August 9, 2016 updated by: Corporal Michael J. Crescenz VA Medical Center
Targeting Wave Reflections to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function in Hypertension
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.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Philadelphia VA Medical Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 89 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / 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.
|
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
|
One capsule of placebo administered once daily at 8 am.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in left ventricular mass
Time Frame: 24 weeks
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in extracellular volume fraction
Time Frame: 24 weeks
|
24 weeks
|
Change in peak myocardial systolic longitudinal strain measured by MRI
Time Frame: 24 weeks
|
24 weeks
|
Change in peak early diastolic intraventricular pressure gradient measured by MRI
Time Frame: 24 weeks
|
24 weeks
|
Change in late systolic hypertension derived from pulse wave analysis
Time Frame: 24 weeks
|
24 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2013
Primary Completion (ACTUAL)
January 1, 2016
Study Completion (ACTUAL)
January 1, 2016
Study Registration Dates
First Submitted
October 9, 2013
First Submitted That Met QC Criteria
October 10, 2013
First Posted (ESTIMATE)
October 11, 2013
Study Record Updates
Last Update Posted (ESTIMATE)
August 11, 2016
Last Update Submitted That Met QC Criteria
August 9, 2016
Last Verified
October 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Pathological Conditions, Anatomical
- Cardiomegaly
- Fibrosis
- Hypertension
- Hypertrophy
- Hypertrophy, Left Ventricular
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Natriuretic Agents
- Diuretics, Osmotic
- Diuretics
- Nitric Oxide Donors
- Isosorbide
- Isosorbide Dinitrate
- Isosorbide-5-mononitrate
Other Study ID Numbers
- 01442
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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