Heart Failure, DiastolicPhase 4HFpEF-PRoFNCT02589977
Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF
A Phase 4 study testing regadenoson in people with Heart Failure, Diastolic and Diastolic Heart Failure, run by Marvin W. Kronenberg, M.D. at 1 site in United States.
Trial summary
Unlike heart failure with reduced ejection fraction (HFrEF) where several medicines and devices have been demonstrated to reduce mortality, no such therapies have been identified in HFpEF. This may be in part due to incomplete understanding of the underlying mechanisms of HFpEF. Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure, Diastolic, Diastolic Heart Failure, Hypertension
- What is being tested?
- regadenoson
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to 21 Jan 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- estimated glomerular filtration rate (eGFR) > 60 ml/min
- preserved left ventricular ejection fraction (>= 50%) on echocardiography
- normal cardiac structure and function on echocardiography
- BP < 140/90
- history of BP >140/90
- 1 or more antihypertensive medications
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- LV ejection fraction (LVEF) at least 50%
- current BP < 160/90
- physician-confirmed diagnosis of HF
- symptomatic HF
- LVEF at least 50%
- elevated LV filling pressure by catheterization, echocardiographic criteria or B-type-natriuretic peptide > 100
- current BP < 160/90
Who cannot join
- coronary artery disease
- diabetes mellitus
- contraindications to cardiac magnetic resonance imaging (CMR)
- weight >350 lbs
- inability to lie flat for imaging
- anemia
Show all 19Show fewer
- contraindications to regadenoson or aminophylline
- HEALTHY
- known cardiovascular disease, cardiac risk factors or use of cardiac medications
- HYPERTENSIVE
- known cardiovascular disease or risk factors aside from hypertension or use of cardiac medications
- HFpEF
- prior history of LVEF below 50%
- acute decompensated HF
- moderate or greater valvular disease
- significant cardiac arrhythmias
- pericardial disease
- congenital heart disease
- primary pulmonary hypertension
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Unlike heart failure with reduced ejection fraction (HFrEF) where several medicines and devices have been demonstrated to reduce mortality, no such therapies have been identified in HFpEF. This may be in part due to incomplete understanding of the underlying mechanisms of HFpEF.
Recently, impaired myocardial blood flow, reduced myocardial energy utilization, and increased myocardial fibrosis have been postulated to play important pathophysiologic roles in HFpEF. The investigators and others have demonstrated that HFrEF may be associated with altered myocardial energy utilization and "energy starvation." However, there are limited data regarding "energy starvation" in HFpEF and the relationships between myocardial blood flow, energy utilization, and fibrosis in HFpEF are largely unknown. Therefore, the purposes of this study are to use non-invasive cardiac imaging techniques to describe cardiac structure, function, blood flow, energetics, and fibrosis, and the relationships between these in order to better understand underlying mechanisms in HFpEF.
Read the detailed description
The investigators hypothesize that HFpEF is associated with reductions in myocardial blood flow and energy utilization and increased myocardial fibrosis as compared to age and gender matched hypertensive and healthy controls. The investigators will test their hypotheses by comparing measurements of myocardial blood flow, energy utilization, and fibrosis between three subject groups (HFpEF vs hypertension vs healthy). Myocardial blood flow will be quantitated from nitrogen (N)13-Ammonia positron emission tomography (PET) and gadolinium enhanced cardiac magnetic resonance (CMR) imaging, both at rest and stress following coronary vasodilation with regadenoson. Myocardial energy utilization will be quantified with 11C-acetate PET imaging and myocardial fibrosis will be assessed with gadolinium enhanced CMR and alterations in myocardial T1. Echocardiography will be utilized to quantify cardiac diastolic function.
It is anticipated that the results of this proposed study will provide a foundation that will inform future studies aimed at identifying novel preventive or therapeutic agents in HFpEF.
- Being tested
- regadenoson
- Keywords
- magnetic resonance imaging, positron-emission tomography, echocardiography, myocardial blood flow, energy metabolism
- Medical subject headings
- Heart Failure, Diastolic, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
regadenosonDrug
Also called positron emission tomography, echocardiography, cardiac magnetic resonance imaging
evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants
| Study group | Role | What they receive |
|---|---|---|
| normal participants | Other | No cardiovascular abnormalities or diabetes. Estimated glomerular filtration rate (eGFR) >60.
Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism. Receives: Drug: regadenoson |
| hypertensive participants | Other | No history of coronary artery disease or diabetes. Estimated glomerular filtration rate (eGFR) >60.
Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism. Receives: Drug: regadenoson |
| HFpEF patients | Other | No history of coronary artery disease or diabetes. Estimated glomerular filtration rate (eGFR) >60.
Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism. Receives: Drug: regadenoson |
What is being measured
The primary outcome is the main question the study is designed to answer.
Coronary Flow Reserve
Rest and regadenoson stress coronary flow reserve by ammonia PET. Coronary flow calculated at rest and again at stress with coronary flow reserve calculated as the ratio of stress to rest coronary flow.
Measured: Baseline study visit
Secondary outcomes (4)
Myocardial Perfusion Reserve by CMR in Each Study Group.
Myocardial perfusion reserve by CMR.
Measured: Baseline study visit.
Extracellular Volume (ECV) by CMR in Each Study Group
Extracellular volume (ECV) by CMR.
Measured: Baseline study visit
Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.
Oxidative metabolism (Kmono/rate pressure product) by PET.
Measured: Baseline study visit
E/e' by Echo in Each Study Group.
E/e' by echo. E is the transmitral peak velocity in early diastole. e' is the early diastolic tissue Doppler velocity average between the septal and lateral mitral annulus. E/e' is the ratio of these two values.
Measured: Baseline study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study startNov 2015
- Primary completion21 Jan 2020
- Study completion21 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, DiastolicStudies 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 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marvin W. Kronenberg, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Responsible party
- Sponsor-investigator, Marvin W. Kronenberg, M.D., Vanderbilt University Medical Center
- Investigators
- Marvin W Kronenberg, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02589977
- Sponsor's protocol ID
- 141686
- Acronym
- HFpEF-PRoF
- Status last verified
- Feb 2021
- First submitted
- 24 Aug 2015
- Last updated
- 2 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bell SP, Adkisson DW, Ooi H, Sawyer DB, Lawson MA, Kronenberg MW. Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy. J Card Fail. 2013 Dec;19(12):802-10. doi: 10.1016/j.cardfail.2013.10.010. Epub 2013 Oct 29.
PubMed 24331202Gupta DK, Shah AM, Castagno D, Takeuchi M, Loehr LR, Fox ER, Butler KR, Mosley TH, Kitzman DW, Solomon SD. Heart failure with preserved ejection fraction in African Americans: The ARIC (Atherosclerosis Risk In Communities) study. JACC Heart Fail. 2013 Apr;1(2):156-63. doi: 10.1016/j.jchf.2013.01.003.
PubMed 23671819
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF
- ClinicalTrials.gov ID
- NCT02589977
- Acronym / sponsor ID
- HFpEF-PRoF / 141686
- Keywords
- magnetic resonance imaging, positron-emission tomography, echocardiography, myocardial blood flow, energy metabolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Marvin W. Kronenberg, M.D.University, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Study start
- Nov 2015
- Primary completion
- 21 Jan 2020 (actual)
- Study completion
- 21 Jan 2020 (actual)
- First posted
- 28 Oct 2015 (estimated)
- Results
- Posted 2 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Unlike heart failure with reduced ejection fraction (HFrEF) where several medicines and devices have been demonstrated to reduce mortality, no such therapies have been identified in HFpEF. This may be in part due to incomplete understanding of the underlying mechanisms of HFpEF.
Recently, impaired myocardial blood flow, reduced myocardial energy utilization, and increased myocardial fibrosis have been postulated to play important pathophysiologic roles in HFpEF. The investigators and others have demonstrated that HFrEF may be associated with altered myocardial energy utilization and "energy starvation." However, there are limited data regarding "energy starvation" in HFpEF and the relationships between myocardial blood flow, energy utilization, and fibrosis in HFpEF are largely unknown. Therefore, the purposes of this study are to use non-invasive cardiac imaging techniques to describe cardiac structure, function, blood flow, energetics, and fibrosis, and the relationships between these in order to better understand underlying mechanisms in HFpEF.
Detailed description
The investigators hypothesize that HFpEF is associated with reductions in myocardial blood flow and energy utilization and increased myocardial fibrosis as compared to age and gender matched hypertensive and healthy controls. The investigators will test their hypotheses by comparing measurements of myocardial blood flow, energy utilization, and fibrosis between three subject groups (HFpEF vs hypertension vs healthy). Myocardial blood flow will be quantitated from nitrogen (N)13-Ammonia positron emission tomography (PET) and gadolinium enhanced cardiac magnetic resonance (CMR) imaging, both at rest and stress following coronary vasodilation with regadenoson. Myocardial energy utilization will be quantified with 11C-acetate PET imaging and myocardial fibrosis will be assessed with gadolinium enhanced CMR and alterations in myocardial T1. Echocardiography will be utilized to quantify cardiac diastolic function.
It is anticipated that the results of this proposed study will provide a foundation that will inform future studies aimed at identifying novel preventive or therapeutic agents in HFpEF.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| normal participants | Other | Drug: regadenosonNo cardiovascular abnormalities or diabetes. Estimated glomerular filtration rate (eGFR) >60. Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism. |
| hypertensive participants | Other | Drug: regadenosonNo history of coronary artery disease or diabetes. Estimated glomerular filtration rate (eGFR) >60. Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism. |
| HFpEF patients | Other | Drug: regadenosonNo history of coronary artery disease or diabetes. Estimated glomerular filtration rate (eGFR) >60. Studies: Echocardiography for left ventricular function and LV diastolic performance; cardiac magnetic resonance (CMR) imaging using gadolinium for LV fibrosis and regadenoson for myocardial blood flow (MBF); positron-emission tomography (PET) using regadenoson for MBF and 11C-acetate for oxidative metabolism. |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- estimated glomerular filtration rate (eGFR) > 60 ml/min
- preserved left ventricular ejection fraction (>= 50%) on echocardiography
- normal cardiac structure and function on echocardiography
- BP < 140/90
- history of BP >140/90
Key exclusion criteria (19 listed)
- coronary artery disease
- diabetes mellitus
- contraindications to cardiac magnetic resonance imaging (CMR)
- weight >350 lbs
- inability to lie flat for imaging
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 |
|---|---|---|
| regadenosonAlso: positron emission tomography, echocardiography, cardiac magnetic resonance imagingevaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants | Drug | HFpEF patients, hypertensive participants, normal participants |
Primary outcome
Coronary Flow Reserve
Time frame: Baseline study visit
Rest and regadenoson stress coronary flow reserve by ammonia PET. Coronary flow calculated at rest and again at stress with coronary flow reserve calculated as the ratio of stress to rest coronary flow.
4 secondary outcomes
Myocardial Perfusion Reserve by CMR in Each Study Group.
Time frame: Baseline study visit.
Extracellular Volume (ECV) by CMR in Each Study Group
Time frame: Baseline study visit
Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group.
Time frame: Baseline study visit
E/e' by Echo in Each Study Group.
Time frame: Baseline study visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24331202Bell SP, Adkisson DW, Ooi H, Sawyer DB, Lawson MA, Kronenberg MW. Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy. J Card Fail. 2013 Dec;19(12):802-10. doi: 10.1016/j.cardfail.2013.10.010. Epub 2013 Oct 29.
- Results publication: PubMed 23671819Gupta DK, Shah AM, Castagno D, Takeuchi M, Loehr LR, Fox ER, Butler KR, Mosley TH, Kitzman DW, Solomon SD. Heart failure with preserved ejection fraction in African Americans: The ARIC (Atherosclerosis Risk In Communities) study. JACC Heart Fail. 2013 Apr;1(2):156-63. doi: 10.1016/j.jchf.2013.01.003.
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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.
Marvin W Kronenberg, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing regadenoson in people with Heart Failure, Diastolic and Diastolic Heart Failure, run by Marvin W. Kronenberg, M.D. 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 13 inclusion and 19 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 2 Feb 2021. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Coronary Flow Reserve (time frame: Baseline study visit). 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 NCT02589977, 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 2 Feb 2021.