Hypertrophic CardiomyopathyNCT00001534
Long Term Effects of Enalapril and Losartan on Genetic Heart Disease
An observational study of Hypertrophic Cardiomyopathy and Left Ventricular Hypertrophy, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
The human heart is divided into four chambers. One of the four chambers, the left ventricle, is the chamber mainly responsible for pumping blood out of the heart into circulation. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypertrophic Cardiomyopathy, Left Ventricular Hypertrophy, Myocardial Ischemia
- What is being tested?
- Losartan
- How many people
- 112 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 1996to Apr 2003
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HCM of either gender, aged 20-55 years.
- Non-dilated LV (LVIDd less than 60 mm) with LV wall thickness of greater than or equal to 16 mm measured in any LV segment by NMR.
- Non-obstructive HCM: A LV outflow gradient of less than or equal to 30 mm Hg gradient at rest and less than or equal to 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization.
- New York Heart Association functional class I-III.
- Patients who have participated in the previous toxicity study may be recruited for this study, if they wish.
- Patients who have previously taken an ACE inhibitor or losartan could only be included in this study, if they have been off these drugs for a period of 6 months or longer.
Who cannot join
- Severe cardiac symptoms at rest (NYHA IV).
- LV outflow tract gradient of greater than 30 mm Hg at rest or greater than 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization.
- Systemic diseases (respiratory, neurologic, or locomotor) that prevent exercise testing, echocardiography or NMR, MUGA, thallium studies, and cardiac catheterization.
- Coronary artery disease (greater than 50% arterial luminal narrowing of a major epicardial vessel) or congenital cardiovascular abnormalities (e.g. ASD, VSD, coronary anomalies).
- Chronic atrial fibrillation.
- Bleeding disorder (PTT greater than 35 sec, pro time greater than 14.7 sec, platelet count less than 154 k/mm3).
Show all 18Show fewer
- Anemia (Hb less than 12.7 g/dl in males and less than 11.0 g/dl in females); renal impairment (BUN greater than 22 mg/dl and serum creatinine greater than 1.4 mg/dl); K+ less than 3.3 mmol/l or greater than 5.1 mmol/l.
- Hypertension: basal systolic and diastolic pressures of greater than 160 mm Hg or greater than 95 mm Hg, respectively on two occasions separated by one hour of rest.
- Hypotension: basal sitting systolic arterial pressure less than 100 mm Hg confirmed 30 minutes later.
- Must have ability to estimate LV wall thickness.
- Radiographic evidence of overt cardiac failure (pulmonary edema on chest X-ray).
- Negative urine pregnancy test.
- Pregnant or lactating female patients.
- Diminished LV systolic function (resting or exercise LV ejection fractions estimated by radionuclide angiography less than 50%).
- Dependence on other cardioactive drugs such as diuretics, verapamil, B-blockers, or antiarrhythmic drugs to control symptoms and arrhythmias.
- Negative HIV test.
- Sensitivity to ACE inhibitor e.g. angioedema.
- Must have ability to set up an outpatient monitoring system.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: Double-Blind, Placebo-Controlled Study of the Long Term Effects of Angiotensin Converting Enzyme Inhibition (Enalapril) and Angiotensin II Receptor Blockade (Losartan) on Genetically-Induced Left Ventricular Hypertrophy in Non-Obstructive HCM
The human heart is divided into four chambers. One of the four chambers, the left ventricle, is the chamber mainly responsible for pumping blood out of the heart into circulation. Hypertrophic cardiomyopathy (HCM) is a genetically inherited disease causing an abnormal thickening of the heart muscle, especially the muscle making up the left ventricle. When the left ventricle becomes abnormally large it is called left ventricular hypertrophy (LVH). This condition can cause symptoms of chest pain, shortness of breath, fatigue, and heart beat palpitations.
This study is designed to compare the ability of two drugs (enalapril and losartan) to improve symptoms and heart function of patients diagnosed with hypertrophic cardiomyopathy (HCM).
Read more
Researchers have decided to compare these drugs because each one has been used to treat patients with other diseases causing thickening of the heart muscle. In these other conditions, enalapril and losartan have improved symptoms, decreased the thickness of heart muscle, improved blood flow and supply to the heart muscle, and improved the pumping action of the heart muscle.
In this study researchers will compare the effectiveness of enalapril and losartan when given separately and together to patients with hypertrophic cardiomyopathy (HCM).
Read the detailed description
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by left ventricular (LV) hypertrophy. There is often associated LV diastolic dysfunction and myocardial ischemia. The severity of the LV hypertrophy, diastolic dysfunction, and myocardial ischemia are important determinants of clinical outcomes. Angiotensin II modulates cell growth and cardiac function. There is also increasing evidence that the renin-angiotensin system (RAS) may be present in cardiac cells, and the hypertrophic action of angiotensin II could therefore be mediated by circulating or locally produced hormone. Animal and clinical studies have demonstrated that independent of their effects on systemic blood pressure, ACE inhibition and angiotensin II receptor (AT1) blockade can reduce cardiac hypertrophy, improve LV diastolic function and myocardial ischemia. AT1 blockade may be preferable to ACE inhibitors because by inhibiting angiotensin II from binding to its receptor, the system can be turned off irrespective of the source of angiotensin II. Also, there may be fewer side effects due to lack of bradykinin. This is a double-blind, placebo-controlled study that examines the abilities of enalapril (ACE inhibition) and losartan (AT1 blockade), separately or in combination, to cause regression of the cardiac hypertrophy, and to improve LV function and myocardial perfusion in non-obstructive HCM.
- Being tested
- Losartan
- Keywords
- Genetics, Myocardial Ischemia, Diastolic Dysfunction, Renin-Angiotensin System, Hypertrophic Cardiomyopathy, Left Ventricular (LV) Hypertrophy
- Medical subject headings
- Cardiomyopathy, Hypertrophic, Hypertrophy, Left Ventricular, Myocardial Ischemia, Hypertrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startSep 1996
- Study completionApr 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hypertrophic CardiomyopathyStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- 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
- Observational
- Enrolment
- 112 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001534
- Sponsor's protocol ID
- 960144
- Other IDs
- 96-H-0144
- Status last verified
- Apr 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Epstein ND, Cohn GM, Cyran F, Fananapazir L. Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the beta-myosin heavy chain gene. A 908Leu----Val mutation and a 403Arg----Gln mutation. Circulation. 1992 Aug;86(2):345-52. doi: 10.1161/01.cir.86.2.345.
PubMed 1638703Fananapazir L, Epstein ND. Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations. Circulation. 1994 Jan;89(1):22-32. doi: 10.1161/01.cir.89.1.22.
PubMed 8281650Maron BJ, Bonow RO, Cannon RO 3rd, Leon MB, Epstein SE. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N Engl J Med. 1987 Mar 26;316(13):780-9. doi: 10.1056/NEJM198703263161305. No abstract available.
PubMed 3547130
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind, Placebo-Controlled Study of the Long Term Effects of Angiotensin Converting Enzyme Inhibition (Enalapril) and Angiotensin II Receptor Blockade (Losartan) on Genetically-Induced Left Ventricular Hypertrophy in Non-Obstructive HCM
- ClinicalTrials.gov ID
- NCT00001534
- Acronym / sponsor ID
- 960144
- Keywords
- Genetics, Myocardial Ischemia, Diastolic Dysfunction, Renin-Angiotensin System, Hypertrophic Cardiomyopathy, Left Ventricular (LV) Hypertrophy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 112 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Sep 1996
- Study completion
- Apr 2003
- First posted
- 4 Nov 1999 (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 human heart is divided into four chambers. One of the four chambers, the left ventricle, is the chamber mainly responsible for pumping blood out of the heart into circulation. Hypertrophic cardiomyopathy (HCM) is a genetically inherited disease causing an abnormal thickening of the heart muscle, especially the muscle making up the left ventricle. When the left ventricle becomes abnormally large it is called left ventricular hypertrophy (LVH). This condition can cause symptoms of chest pain, shortness of breath, fatigue, and heart beat palpitations.
This study is designed to compare the ability of two drugs (enalapril and losartan) to improve symptoms and heart function of patients diagnosed with hypertrophic cardiomyopathy (HCM).
Researchers have decided to compare these drugs because each one has been used to treat patients with other diseases causing thickening of the heart muscle. In these other conditions, enalapril and losartan have improved symptoms, decreased the thickness of heart muscle, improved blood flow and supply to the heart muscle, and improved the pumping action of the heart muscle.
In this study researchers will compare the effectiveness of enalapril and losartan when given separately and together to patients with hypertrophic cardiomyopathy (HCM).
Detailed description
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by left ventricular (LV) hypertrophy. There is often associated LV diastolic dysfunction and myocardial ischemia. The severity of the LV hypertrophy, diastolic dysfunction, and myocardial ischemia are important determinants of clinical outcomes. Angiotensin II modulates cell growth and cardiac function. There is also increasing evidence that the renin-angiotensin system (RAS) may be present in cardiac cells, and the hypertrophic action of angiotensin II could therefore be mediated by circulating or locally produced hormone. Animal and clinical studies have demonstrated that independent of their effects on systemic blood pressure, ACE inhibition and angiotensin II receptor (AT1) blockade can reduce cardiac hypertrophy, improve LV diastolic function and myocardial ischemia. AT1 blockade may be preferable to ACE inhibitors because by inhibiting angiotensin II from binding to its receptor, the system can be turned off irrespective of the source of angiotensin II. Also, there may be fewer side effects due to lack of bradykinin. This is a double-blind, placebo-controlled study that examines the abilities of enalapril (ACE inhibition) and losartan (AT1 blockade), separately or in combination, to cause regression of the cardiac hypertrophy, and to improve LV function and myocardial perfusion in non-obstructive HCM.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- HCM of either gender, aged 20-55 years.
- Non-dilated LV (LVIDd less than 60 mm) with LV wall thickness of greater than or equal to 16 mm measured in any LV segment by NMR.
- Non-obstructive HCM: A LV outflow gradient of less than or equal to 30 mm Hg gradient at rest and less than or equal to 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization.
- New York Heart Association functional class I-III.
- Patients who have participated in the previous toxicity study may be recruited for this study, if they wish.
Key exclusion criteria (18 listed)
- Severe cardiac symptoms at rest (NYHA IV).
- LV outflow tract gradient of greater than 30 mm Hg at rest or greater than 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization.
- Systemic diseases (respiratory, neurologic, or locomotor) that prevent exercise testing, echocardiography or NMR, MUGA, thallium studies, and cardiac catheterization.
- Coronary artery disease (greater than 50% arterial luminal narrowing of a major epicardial vessel) or congenital cardiovascular abnormalities (e.g. ASD, VSD, coronary anomalies).
- Chronic atrial fibrillation.
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 |
|---|---|---|
| Losartan | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 1638703Epstein ND, Cohn GM, Cyran F, Fananapazir L. Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the beta-myosin heavy chain gene. A 908Leu----Val mutation and a 403Arg----Gln mutation. Circulation. 1992 Aug;86(2):345-52. doi: 10.1161/01.cir.86.2.345.
- Background: PubMed 8281650Fananapazir L, Epstein ND. Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations. Circulation. 1994 Jan;89(1):22-32. doi: 10.1161/01.cir.89.1.22.
- Background: PubMed 3547130Maron BJ, Bonow RO, Cannon RO 3rd, Leon MB, Epstein SE. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N Engl J Med. 1987 Mar 26;316(13):780-9. doi: 10.1056/NEJM198703263161305. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypertrophic Cardiomyopathy and Left Ventricular Hypertrophy, run by National Heart, Lung, and Blood Institute (NHLBI) 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 6 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: finished, as of the sponsor's last update on 4 Mar 2008. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001534, which also lists 3 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 4 Mar 2008.