Cardiovascular Manifestations of MR Activation in Primary Aldosteronism: Pilot Clinical Study

Study Overview
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Brief Summary
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This research study aims to learn more about the impact the hormone aldosterone on the heart. Primary aldosteronism is a condition where the body's adrenal glands make too much of the hormone aldosterone, which can cause high blood pressure and increase the risk of heart and kidney disease. Treatment with medications that block aldosterone can reduce that risk. This study is trying to learn whether treatment with a medication that blocks aldosterone can improve heart function in people who make too much aldosterone.

Detailed Description
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The study evaluates the impact of 6 months of treatment with the mineralocorticoid receptor blocking medication eplerenone on the heart's blood flow, using a cardiac PET stress test, and on the heart's structure and function by echocardiogram. Participants with a confirmed diagnosis of primary aldosteronism will undergo echocardiogram and cardiac PET stress test before and after 6 months of eplerenone treatment. Participants without a confirmed diagnosis of primary aldosteronism but with hypertension and a recent clinical PET test and echocardiogram will undergo testing to make the diagnosis of primary aldosteronism. Those who test positive will go on to treatment with eplerenone for 6 months, followed by a cardiac PET scan and echocardiogram.

Official Title
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Cardiovascular Manifestations of MR Activation in Primary Aldosteronism: Pilot Clinical Study

Conditions
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Primary Aldosteronism, Hypertension

Intervention / Treatment
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* Drug: Eplerenone


Participation Criteria
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Eligibility Criteria
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Cohort A: Overt & Diagnosed PA Inclusion Criteria: Adults aged 18-85 Able to provide informed consent and willing to comply with the study Able to fit safely in PET/CT scanner (weight limit 500 pounds; diameter and circumference of PET/CT scanner are 70 cm and 220 cm, respectively) Hypertension treated with at least one antihypertensive drug Cohort A: Clinically confirmed diagnosis of PA not yet treated with mineralocorticoid receptor antagonists Exclusion Criteria: History of MI, CABG, known cardiomyopathy (EF <40%, hypertrophic cardiomyopathy, and/or amyloid), cardiac transplantation Contraindication or allergy to eplerenone or spironolactone Current pregnancy or breastfeeding eGFR < 45 mL/min/1.73m2 or potassium > 5.1 on labs within the preceding 3 months Cohort A: Planned adrenalectomy in the subsequent 6 months Cohort B: Subclinical & Undiagnosed PA Inclusion Criteria: Adults aged 18-85 Able to provide informed consent and willing to comply with the study Able to fit safely in PET/CT scanner (weight limit 500 pounds; diameter and circumference of PET/CT scanner are 70 cm and 220 cm, respectively) Hypertension treated with at least one antihypertensive drug Cohort B: Clinically indicated cardiac PET perfusion scan within the preceding 3 months and echocardiogram within the preceding 6 months Exclusion Criteria: History of MI, CABG, known cardiomyopathy (EF <40%, hypertrophic cardiomyopathy, and/or amyloid), cardiac transplantation Contraindication or allergy to eplerenone or spironolactone Current pregnancy or breastfeeding eGFR < 45 mL/min/1.73m2 or potassium > 5.1 on labs within the preceding 3 months Cohort B: 10% or greater burden of ischemia on qualifying PET Cohort B: Planned coronary angiogram/revascularization in the subsequent 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eplerenone Treatment<br>Eplerenone (50-100mg daily, as tolerated by blood pressure and potassium) for 6 months | Drug: Eplerenone<br>* After baseline cardiac imaging with PET and echocardiogram, participants will be treated with eplerenone for 6 months at a starting dose of 50mg daily and up to a maximally tolerated dose of 100mg daily, followed by repeat imaging with PET and echocardiogram.<br>* Other names: Mineralocorticoid Receptor Antagonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in myocardial flow reserve (MFR, unitless ratio) | The primary outcome is to evaluate the change in MFR, as measured by PET, pre- vs post-6 months of eplerenone therapy | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in peak-stress myocardial blood flow (ml/min/g) | Peak stress myocardial blood flow is measured by PET after vasodilator-induced maximal hyperemia, before and after 6 months of eplerenone treatment | 6 months | 
| Change in Global Longitudinal Strain (%) | Global Longitudinal Strain is measured by echocardiography before and after 6 months of eplerenone treatment | 6 months | 
| Change in LV Mass Index (g/m2 of body surface area) | LV Mass Index is measured by echocardiography before and after 6 months of eplerenone treatment | 6 months |