Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Philadelphia Veterans Affairs Medical Center
Sponsor:
Information provided by (Responsible Party):
Philadelphia Veterans Affairs Medical Center
ClinicalTrials.gov Identifier:
NCT01961453
First received: October 9, 2013
Last updated: October 27, 2014
Last verified: October 2014

October 9, 2013
October 27, 2014
August 2013
August 2015   (final data collection date for primary outcome measure)
Change in left ventricular mass [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01961453 on ClinicalTrials.gov Archive Site
  • Change in extracellular volume fraction [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in peak myocardial systolic longitudinal strain measured by MRI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in peak early diastolic intraventricular pressure gradient measured by MRI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in late systolic hypertension derived from pulse wave analysis [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Effect of Isosorbide Mononitrate on Hypertension to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypertension
  • Drug: Isosorbide Mononitrate, sustained release
    60 mg if Titration Stage 1 OR 120 mg if Titration Stage 2
  • Drug: Placebo capsule
    One capsule of placebo administered once daily at 8 am.
  • 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.
    Intervention: Drug: Isosorbide Mononitrate, sustained release
  • Placebo Comparator: Placebo capsule
    One capsule of placebo administered once daily at 8 AM
    Intervention: Drug: Placebo capsule

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
46
August 2015
August 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years to 89 Years
No
Contact: Julio A Chirinos, MD, PhD 215-823-5800 ext 6791 julio.chirinos@uphs.upenn.edu
United States
 
NCT01961453
01442
No
Philadelphia Veterans Affairs Medical Center
Philadelphia Veterans Affairs Medical Center
Not Provided
Principal Investigator: Julio A Chirinos, MD, PhD Philadelphia VA Medical Center & University of Pennsylvania
Philadelphia Veterans Affairs Medical Center
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP