HypertensionPhase 2ISMNNCT01961453
Effect of Isosorbide Mononitrate on Hypertension to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function
A Phase 2 study testing Isosorbide Mononitrate, sustained release in people with Hypertension, run by Corporal Michael J. Crescenz VA Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Isosorbide Mononitrate, sustained release
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Jan 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
- Conditions
- Hypertension
- Being tested
- Isosorbide Mononitrate, sustained release, Placebo capsule
- Keywords
- Hypertension, Isosorbide Mononitrate, Myocardial fibrosis
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isosorbide Mononitrate, sustained releaseDrug
60 mg if Titration Stage 1 OR 120 mg if Titration Stage 2
Placebo capsuleDrug
One capsule of placebo administered once daily at 8 am.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Isosorbide Mononitrate, sustained release |
| Placebo capsule | Placebo comparator | One capsule of placebo administered once daily at 8 AM Receives: Drug: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricular mass
Measured: 24 weeks
Secondary outcomes (4)
Change in extracellular volume fraction
Measured: 24 weeks
Change in peak myocardial systolic longitudinal strain measured by MRI
Measured: 24 weeks
Change in peak early diastolic intraventricular pressure gradient measured by MRI
Measured: 24 weeks
Change in late systolic hypertension derived from pulse wave analysis
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2013 (estimated)
- Study startAug 2013
- Primary completionJan 2016
- Study completionJan 2016
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corporal Michael J. Crescenz VA Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Julio A Chirinos, MD, PhD, Principal investigator, Philadelphia VA Medical Center & University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01961453
- Sponsor's protocol ID
- 01442
- Acronym
- ISMN
- Status last verified
- Oct 2014
- First submitted
- 9 Oct 2013
- Last updated
- 11 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Bradley JG, Davis KA. Orthostatic hypotension. Am Fam Physician. 2003 Dec 15;68(12):2393-8.
PubMed 14705758Li 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.
PubMed 21240870
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Wave Reflections to Improve Left Ventricular Hypertrophy, Fibrosis and Myocardial Function in Hypertension
- ClinicalTrials.gov ID
- NCT01961453
- Acronym / sponsor ID
- ISMN / 01442
- Conditions
- Hypertension
- Keywords
- Hypertension, Isosorbide Mononitrate, Myocardial fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Corporal Michael J. Crescenz VA Medical CenterUS federal agency
- Study start
- Aug 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 11 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Isosorbide Mononitrate, sustained release | Active comparator | Drug: Isosorbide Mononitrate, sustained releaseOne tablet containing 60 mg (Titration Stage 1) OR 120 mg (Titration Stage 2) of sustained-release ISMN administered at 8 AM. |
| Placebo capsule | Placebo comparator | Drug: Placebo capsuleOne capsule of placebo administered once daily at 8 AM |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isosorbide Mononitrate, sustained release60 mg if Titration Stage 1 OR 120 mg if Titration Stage 2 | Drug | Isosorbide Mononitrate, sustained release |
| Placebo capsuleOne capsule of placebo administered once daily at 8 am. | Drug | Placebo capsule |
Primary outcome
Change in left ventricular mass
Time frame: 24 weeks
4 secondary outcomes
Change in extracellular volume fraction
Time frame: 24 weeks
Change in peak myocardial systolic longitudinal strain measured by MRI
Time frame: 24 weeks
Change in peak early diastolic intraventricular pressure gradient measured by MRI
Time frame: 24 weeks
Change in late systolic hypertension derived from pulse wave analysis
Time frame: 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2016.
- Background: PubMed 14705758Bradley JG, Davis KA. Orthostatic hypotension. Am Fam Physician. 2003 Dec 15;68(12):2393-8.
- Background: PubMed 21240870Li 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julio A Chirinos, MD, PhD principal investigator
Philadelphia VA Medical Center & University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isosorbide Mononitrate, sustained release in people with Hypertension, run by Corporal Michael J. Crescenz VA Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in left ventricular mass (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01961453, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2016.