Heart Failure With Preserved Ejection FractionNCT01354613
Reduced Contractile Reserve: a Therapeutic Target in Heart Failure With Preserved Ejection Fraction(HFpEF)
A study testing Dobutamine and Amlodipine in people with Heart Failure With Preserved Ejection Fraction and Pulmonary Disease, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of heart failure cases in the United States, affecting a primarily elderly population. No treatment has been shown to affect mortality in HFpEF, which is more than 50% at five years a hospitalization. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Pulmonary Disease, Left Ventricular Hypertrophy/Hypertension
- What is being tested?
- Dobutamine and Amlodipine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Dec 2013
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female; Age 18 or older.
- Left ventricular ejection fraction ≥ 50%.
- Symptomatic heart failure or appropriate comparator group criteria
- Informed consent signed by the subject
Who cannot join
- Symptoms of active ischemia.
- Moderate or severe mitral or aortic stenosis, or severe aortic insufficiency.
- Serum creatinine > 3.0 or chronic hemodialysis.
- Known chronic hepatic disease; defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 3.0 times the upper limit of normal as read at the local lab.
- Severe renal dysfunction, i.e. glomerular filtration rate (GFR) <30 ml/min.
- Atrial fibrillation
Show all 33Show fewer
- Myocardial infarction within the last year
- Coronary bypass surgery within the last 6 months
- Stroke within the last 6 months
- Known aortic aneurysm
- Contra-indication to withdrawal of beta blocker or antihypertensive medications
- Resting or orthostatic hypotension (SBP < 90 mmHg)
- Any gastrointestinal disorder which would interfere with drug absorption
- Any significant valvular heart disease, including prior multiple valve replacement.
- Pericardial Disease
- Infiltrative or hypertrophic cardiomyopathy
- Cor pulmonale
- Unstable coronary disease
- Pregnancy
- Any condition which may prevent the subject from adhering to the study protocol, as determined by the investigator
- Heart Failure with Preserved Ejection Fraction
- Clinical evidence of heart failure with preserved ejection fraction, as manifest by at least 2 symptoms or signs, including dyspnea on exertion or at rest, orthopnea, jugular venous distention or hepatojugular reflux, rales or edema.
- Controlled systolic BP (< 150 mmHg on the day of study)
- Pulmonary Disease Group
- Known obstructive airways disease with objective documentation of an isolated obstructive defect by pulmonary function testing.
- No history of heart failure.
- No history of cardiovascular disease, with the exception of hypertension or hyperlipidemia
- History and physical examination free of signs and symptoms of heart failure, including elevated jugular venous pressure, hepatojugular reflux, rales or edema.
- Baseline echocardiographic examination without evidence of heart failure, including systolic dysfunction of the LV or RV, or evidence of more than mild diastolic dysfunction on non-invasive assessment.
- HTN/LVH Group
- Known history of hypertension.
- Echocardiographic evidence of left ventricular hypertrophy and diastolic dysfunction.
- No history or physical examination evidence of heart failure, including excessive dyspnea on exertion, dyspnea at rest, orthopnea, PND, jugular venous distention, hepatojugular reflux, rales or edema.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Reduced Contractile Reserve: a Therapeutic Target in Heart Failure With Preserved Ejection Fraction
Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of heart failure cases in the United States, affecting a primarily elderly population. No treatment has been shown to affect mortality in HFpEF, which is more than 50% at five years a hospitalization. This project explores the underlying cardiovascular physiology of patients with HFpEF with the goal of identifying new therapeutic targets that would allow improved treatment of this devastating disease.
Read the detailed description
Heart failure with preserved ejection fraction (HFpEF) is a difficult disease to diagnose due to nonspecific symptoms and clinical findings. The disease occurs in the elderly, who often have other illnesses and signs of aging that make diagnosis of heart failure more difficult. Recently, it has been suggested that HFpEF, which has primarily been thought to be a diastolic disease, is in fact multifactorial, with elements of abnormal systolic function and increased vascular stiffness playing a role in disease pathology. No treatment has been shown to reduce the high mortality of the disease. However, few studies have evaluated this population of patients during periods of increased physiologic stress, despite the consistent clinical presentation of impaired exercise tolerance with few symptoms at rest. This study explores the multifactorial physiology of HFpEF, with a detailed investigation of the specificity of abnormalities in contractile reserve and vascular stiffness for this disease, and exploration of the modifiability of these abnormalities. The techniques used are non-invasive, involving echocardiographic evaluation of cardiac function, and measurement of arterial stiffness using tonometry. The first aim of the study is to explore the specificity of a potential diagnostic test for HFpEF by investigating the change in ejection fraction before and after β-adrenergic stimulation with low-dose dobutamine in HFpEF compared to other groups important to distinguish clinically, specifically patients with shortness of breath due to pulmonary disease, and those with hypertension and left ventricular hypertrophy without clinical heart failure. In the second aim, the study will investigate the ability of the calcium channel blocker, amlodipine, to restore normal contractile responses of the myocardium. In the third aim, the role of arterial stiffness in drug responses in HFpEF will be explored. It is anticipated that improved understanding of the complex physiology of this multifactorial disease gained through this study will lead to more rational design of large clinical trials studying promising agents for HFpEF that impact not only diastolic function, but contractile reserve and arterial properties as well.
- Conditions
- Heart Failure With Preserved Ejection Fraction, Pulmonary Disease, Left Ventricular Hypertrophy/Hypertension
- Being tested
- Dobutamine, Amlodipine
- Medical subject headings
- Lung Diseases, Hypertrophy, Left Ventricular, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DobutamineDrug
IV administration at the initial study visit (all groups) and at the final study visit for the drug intervention arm (HFpEF group only). Administration of low-dose dobutamine at 5mcg/kg/min and 10mcg/kg/min for periods of approximately 30minutes/dose for purposes of performing a low-dose stress exam on the heart.
AmlodipineDrug
Participants will be randomized to treatment with either amlodipine 5 mg daily or placebo, in double-blind fashion, 25 patients in each group. 12 week oral administration of 5mg/day, uptitrated to 10mg/day, determined by PI.
| Study group | Role | What they receive |
|---|---|---|
| HFpEF | Experimental | 25 patients with clinically diagnosed heart failure with preserved ejection fraction, confirmed by Framingham criteria, with EF > 50% and without evidence of active ischemia or known severe CAD, valvular or pericardial disease, infiltrative or hypertrophic cardiomyopathy, cor pulmonale, severe pulmonary disease, or primary renal disease. Subjects will receive amlodipine, oral administration for a period of 12 weeks. Receives: Drug: Dobutamine; Drug: Amlodipine |
| Pulmonary Disease | Experimental | 20 patients with pulmonary disease and no clinical evidence of cardiovascular disease Receives: Drug: Dobutamine |
| LVH/HTN | Experimental | 20 subjects with known left ventricular hypertrophy and clinically diagnosed hypertension without the diagnosis of heart failure. Receives: Drug: Dobutamine |
| HFpEF placebo | Placebo comparator | 25 patients with clinically diagnosed heart failure with preserved ejection fraction, confirmed by Framingham criteria, with EF > 50% and without evidence of active ischemia or known severe CAD, valvular or pericardial disease, infiltrative or hypertrophic cardiomyopathy, cor pulmonale, severe pulmonary disease, or primary renal disease. Subjects will be administered a placebo for a period of 12 weeks. Receives: Drug: Dobutamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ejection fraction with 5mcg/kg/min dobutamine
The primary outcome variable in this analysis will be change in ejection fraction from baseline at the 5 mcg dobutamine dose.
Measured: day 0 and 12 week study visit
Change in pulse wave velocity
Change in carotid-femoral pulse wave velocity (PWV) with 12 weeks of therapy with amlodipine or placebo will be the primary outcome variable.
Measured: 12 week study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2011 (estimated)
- Study startApr 2011
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Nancy K Sweitzer, MD, PhD, Principal investigator, UW-Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01354613
- Sponsor's protocol ID
- H-2010-0061
- Other IDs
- R21HL106103-01
- Status last verified
- Apr 2019
- First submitted
- 5 May 2011
- Last updated
- 11 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Contractile Reserve: a Therapeutic Target in Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT01354613
- Acronym / sponsor ID
- H-2010-0061
- Conditions
- Heart Failure With Preserved Ejection Fraction, Pulmonary Disease, Left Ventricular Hypertrophy/Hypertension
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Apr 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 17 May 2011 (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.
Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of heart failure cases in the United States, affecting a primarily elderly population. No treatment has been shown to affect mortality in HFpEF, which is more than 50% at five years a hospitalization. This project explores the underlying cardiovascular physiology of patients with HFpEF with the goal of identifying new therapeutic targets that would allow improved treatment of this devastating disease.
Detailed description
Heart failure with preserved ejection fraction (HFpEF) is a difficult disease to diagnose due to nonspecific symptoms and clinical findings. The disease occurs in the elderly, who often have other illnesses and signs of aging that make diagnosis of heart failure more difficult. Recently, it has been suggested that HFpEF, which has primarily been thought to be a diastolic disease, is in fact multifactorial, with elements of abnormal systolic function and increased vascular stiffness playing a role in disease pathology. No treatment has been shown to reduce the high mortality of the disease. However, few studies have evaluated this population of patients during periods of increased physiologic stress, despite the consistent clinical presentation of impaired exercise tolerance with few symptoms at rest. This study explores the multifactorial physiology of HFpEF, with a detailed investigation of the specificity of abnormalities in contractile reserve and vascular stiffness for this disease, and exploration of the modifiability of these abnormalities. The techniques used are non-invasive, involving echocardiographic evaluation of cardiac function, and measurement of arterial stiffness using tonometry. The first aim of the study is to explore the specificity of a potential diagnostic test for HFpEF by investigating the change in ejection fraction before and after β-adrenergic stimulation with low-dose dobutamine in HFpEF compared to other groups important to distinguish clinically, specifically patients with shortness of breath due to pulmonary disease, and those with hypertension and left ventricular hypertrophy without clinical heart failure. In the second aim, the study will investigate the ability of the calcium channel blocker, amlodipine, to restore normal contractile responses of the myocardium. In the third aim, the role of arterial stiffness in drug responses in HFpEF will be explored. It is anticipated that improved understanding of the complex physiology of this multifactorial disease gained through this study will lead to more rational design of large clinical trials studying promising agents for HFpEF that impact not only diastolic function, but contractile reserve and arterial properties as well.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HFpEF | Experimental | Drug: Dobutamine, Drug: Amlodipine25 patients with clinically diagnosed heart failure with preserved ejection fraction, confirmed by Framingham criteria, with EF > 50% and without evidence of active ischemia or known severe CAD, valvular or pericardial disease, infiltrative or hypertrophic cardiomyopathy, cor pulmonale, severe pulmonary disease, or primary renal disease. Subjects will receive amlodipine, oral administration for a period of 12 weeks. |
| Pulmonary Disease | Experimental | Drug: Dobutamine20 patients with pulmonary disease and no clinical evidence of cardiovascular disease |
| LVH/HTN | Experimental | Drug: Dobutamine20 subjects with known left ventricular hypertrophy and clinically diagnosed hypertension without the diagnosis of heart failure. |
| HFpEF placebo | Placebo comparator | Drug: Dobutamine25 patients with clinically diagnosed heart failure with preserved ejection fraction, confirmed by Framingham criteria, with EF > 50% and without evidence of active ischemia or known severe CAD, valvular or pericardial disease, infiltrative or hypertrophic cardiomyopathy, cor pulmonale, severe pulmonary disease, or primary renal disease. Subjects will be administered a placebo for a period of 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female; Age 18 or older.
- Left ventricular ejection fraction ≥ 50%.
- Symptomatic heart failure or appropriate comparator group criteria
- Informed consent signed by the subject
Key exclusion criteria (33 listed)
- Symptoms of active ischemia.
- Moderate or severe mitral or aortic stenosis, or severe aortic insufficiency.
- Serum creatinine > 3.0 or chronic hemodialysis.
- Known chronic hepatic disease; defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 3.0 times the upper limit of normal as read at the local lab.
- Severe renal dysfunction, i.e. glomerular filtration rate (GFR) <30 ml/min.
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 |
|---|---|---|
| DobutamineIV administration at the initial study visit (all groups) and at the final study visit for the drug intervention arm (HFpEF group only). Administration of low-dose dobutamine at 5mcg/kg/min and 10mcg/kg/min for periods of approximately 30minutes/dose for purposes of performing a low-dose stress exam on the heart. | Drug | HFpEF, HFpEF placebo, LVH/HTN, Pulmonary Disease |
| AmlodipineParticipants will be randomized to treatment with either amlodipine 5 mg daily or placebo, in double-blind fashion, 25 patients in each group. 12 week oral administration of 5mg/day, uptitrated to 10mg/day, determined by PI. | Drug | HFpEF |
Primary outcome
Change in ejection fraction with 5mcg/kg/min dobutamine
Time frame: day 0 and 12 week study visit
The primary outcome variable in this analysis will be change in ejection fraction from baseline at the 5 mcg dobutamine dose.
Change in pulse wave velocity
Time frame: 12 week study visit
Change in carotid-femoral pulse wave velocity (PWV) with 12 weeks of therapy with amlodipine or placebo will be the primary outcome variable.
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 11 Apr 2019.
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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.
Nancy K Sweitzer, MD, PhD principal investigator
UW-Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dobutamine and Amlodipine in people with Heart Failure With Preserved Ejection Fraction and Pulmonary Disease, run by University of Wisconsin, Madison 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 33 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 11 Apr 2019. 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.
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.
What does the primary outcome measure?
Change in ejection fraction with 5mcg/kg/min dobutamine (time frame: day 0 and 12 week study visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Apr 2019.