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| Name | Class |
|---|---|
| Astellas Pharma US, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| regadenoson | Drug | evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline study visit |
| Measure | Description | Time Frame |
|---|---|---|
| Myocardial Perfusion Reserve by CMR in Each Study Group. | Myocardial perfusion reserve by CMR. | Baseline study visit. |
| Extracellular Volume (ECV) by CMR in Each Study Group | Extracellular volume (ECV) by CMR. |
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ALL
Inclusion Criteria:
Exclusion Criteria:
HEALTHY
Inclusion criteria:
Exclusion criteria:
HYPERTENSIVE
Inclusion criteria:
Exclusion criteria:
HFpEF
Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marvin W Kronenberg, MD | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24331202 | Result | 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. | |
| 23671819 | Result | Gupta 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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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Participants | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
| FG001 | Hypertensive Participants | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
| FG002 | HFpEF Patients | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
These are the people who attended baseline visit.
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Participants | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Incomplete data for 18 because of either inability to complete scan OR scan quality not adequate for analysis. | Posted | Median | Inter-Quartile Range | ratio | Baseline study visit |
|
This is a cross sectional study. Subjects were followed for adverse events between screening/enrollment to one day following completion of the cardiac imaging study visit. Because this was not a longitudinal study with serial measurements of the end points the time between enrollment and cross sectional cardiac imaging study visit was variable for each subject in accordance with the study protocol. All subjects completed study procedures within thirteen months of enrollment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Normal Participants | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marvin Kronenberg, MD | Vanderbilt University Medical Center | 615-322-2318 | marvin.w.kronenberg@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 10, 2019 | Dec 15, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D054144 | Heart Failure, Diastolic |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C430916 | regadenoson |
| D009682 | Magnetic Resonance Spectroscopy |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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|
| Baseline study visit |
| Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group. | Oxidative metabolism (Kmono/rate pressure product) by PET. | 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. | Baseline study visit |
| BG001 | Hypertensive Participants | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
| BG002 | HFpEF Patients | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hypertension | Count of Participants | Participants |
|
| Diabetes | Count of Participants | Participants |
|
| BMI | Median | Inter-Quartile Range | kg/m^2 |
|
| OG001 | Hypertensive Participants | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
| OG002 | HFpEF Patients | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants |
|
|
| Secondary | Myocardial Perfusion Reserve by CMR in Each Study Group. | Myocardial perfusion reserve by CMR. | Incomplete data for 10 because of either inability to complete scan OR scan quality not adequate for analysis. | Posted | Median | Inter-Quartile Range | ratio | Baseline study visit. |
|
|
|
| Secondary | Extracellular Volume (ECV) by CMR in Each Study Group | Extracellular volume (ECV) by CMR. | Incomplete data for 9 because of either inability to complete scan OR scan quality not adequate for analysis. | Posted | Median | Inter-Quartile Range | percent ECV | Baseline study visit |
|
|
|
| Secondary | Oxidative Metabolism (Kmono/Rate Pressure Product) by PET in Each Study Group. | Oxidative metabolism (Kmono/rate pressure product) by PET. | Incomplete data for 4 because of either inability to complete scan OR scan quality not adequate for analysis. | Posted | Median | Inter-Quartile Range | min-1/(beats/min x mmhg) | Baseline study visit |
|
|
|
| Secondary | 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. | We were able to collect data on all participants who completed the study. | Posted | Median | Inter-Quartile Range | ratio | Baseline study visit |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | Hypertensive Participants | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants | 0 | 20 | 0 | 20 | 0 | 20 |
| EG002 | HFpEF Patients | 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. regadenoson: evaluation of myocardial blood flow, interstitial fibrosis and oxidative metabolism in HFpEF, compared to hypertensive and normal participants | 0 | 12 | 0 | 12 | 0 | 12 |
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