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

Hypertension Clinical Trial

— ISMN  

Official title:

Targeting Wave Reflections to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function in Hypertension

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01961453
• Other study ID #: 01442
• Status: Withdrawn
• Phase: Phase 2
• First received: October 9, 2013
• Last updated: August 9, 2016
• Start date: August 2013
• Est. completion date: January 2016

Study information

• Verified date: October 2014
• Source: Corporal Michael J. Crescenz VA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 89 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Hypertension
• Hypertrophy
• Hypertrophy, Left Ventricular

Intervention

Drug:
• Isosorbide Mononitrate, sustained release
60 mg if Titration Stage 1 OR 120 mg if Titration Stage 2
• Placebo capsule
One capsule of placebo administered once daily at 8 am.

Locations

Country	Name	City	State
United States	Philadelphia VA Medical Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Corporal Michael J. Crescenz VA Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bradley JG, Davis KA. Orthostatic hypotension. Am Fam Physician. 2003 Dec 15;68(12):2393-8. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in left ventricular mass		24 weeks	No
Secondary	Change in extracellular volume fraction		24 weeks	No
Secondary	Change in peak myocardial systolic longitudinal strain measured by MRI		24 weeks	No
Secondary	Change in peak early diastolic intraventricular pressure gradient measured by MRI		24 weeks	No
Secondary	Change in late systolic hypertension derived from pulse wave analysis		24 weeks	No