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

NCT01961453 | Withdrawn Phase 2

• 1 other identifier: 01442
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

Hypertension; Isosorbide Mononitrate; Myocardial fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular mass

  24 weeks

Secondary Outcomes (4)

• Change in extracellular volume fraction

  24 weeks

• Change in peak myocardial systolic longitudinal strain measured by MRI

  24 weeks

• Change in peak early diastolic intraventricular pressure gradient measured by MRI

  24 weeks

• Change in late systolic hypertension derived from pulse wave analysis

  24 weeks

Study Arms (2)

Isosorbide Mononitrate, sustained release

ACTIVE COMPARATOR

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

Placebo capsule

PLACEBO COMPARATOR

One capsule of placebo administered once daily at 8 AM

Drug: Placebo capsule

Interventions

Isosorbide Mononitrate, sustained release DRUG

60 mg if Titration Stage 1 OR 120 mg if Titration Stage 2

Isosorbide Mononitrate, sustained release

Placebo capsule DRUG

One capsule of placebo administered once daily at 8 am.

Placebo capsule

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Corporal Michael J. Crescenz VA Medical Center: lead

Study Sites (1)

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

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

  PMID: 14705758 BACKGROUND

• 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. doi: 10.5301/jn.2011.6252.

  PMID: 21240870 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

isosorbide-5-mononitrate

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Julio A Chirinos, MD, PhD

  Philadelphia VA Medical Center & University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2013
• First Posted: October 11, 2013
• Study Start: August 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: August 11, 2016

Record last verified: 2014-10

Locations

US (1)