Effect of Isosorbide Mononitrate on Hypertension to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function
Information source: Philadelphia Veterans Affairs Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension
Intervention: Isosorbide Mononitrate, sustained release (Drug); Placebo capsule (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Philadelphia Veterans Affairs Medical Center Official(s) and/or principal investigator(s): Julio A Chirinos, MD, PhD, Principal Investigator, Affiliation: Philadelphia VA Medical Center & University of Pennsylvania
Overall contact: Julio A Chirinos, MD, PhD, Phone: 215-823-5800, Ext: 6791, Email: julio.chirinos@uphs.upenn.edu
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.
Clinical Details
Official title: Targeting Wave Reflections to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function in Hypertension
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change in left ventricular mass
Secondary outcome: Change in extracellular volume fractionChange in peak myocardial systolic longitudinal strain measured by MRI Change in peak early diastolic intraventricular pressure gradient measured by MRI Change in late systolic hypertension derived from pulse wave analysis
Eligibility
Minimum age: 18 Years.
Maximum age: 89 Years.
Gender(s): Both.
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.
Locations and Contacts
Julio A Chirinos, MD, PhD, Phone: 215-823-5800, Ext: 6791, Email: julio.chirinos@uphs.upenn.edu
Philadelphia VA Medical Center, Philadelphia, Pennsylvania 19104, United States; Recruiting Julio A Chirinos, MD, PhD, Phone: 215-200-7779, Email: julio.chirinos@uphs.upenn.edu Julio A Chirinos, MD, PhD, Principal Investigator
Additional Information
Related publications: Bradley JG, Davis KA. Orthostatic hypotension. Am Fam Physician. 2003 Dec 15;68(12):2393-8. Review. Li H, Wang SX. Improvement of hypertension and LVH in maintenance hemodialysis patients treated with sustained-release isosorbide mononitrate. J Nephrol. 2011 Mar-Apr;24(2):236-45.
Starting date: August 2013
Last updated: October 27, 2014
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