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

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Primary Aldosteronism
• Intervention / Treatment: Drug: Eplerenone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jenifer M Brown, MD; Phone Number: 8573071990; Email: jbrown35@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Eva Abel; Phone Number: 617-525-3803

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eplerenone Treatment; Eplerenone (50-100mg daily, as tolerated by blood pressure and potassium) for 6 months	Drug: Eplerenone; 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.; Other Names: Inspra; Mineralocorticoid Receptor Antagonist

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Hyperaldosteronism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Diuretics; Natriuretic Agents; Antihypertensive Agents; Diuretics, Potassium Sparing; Eplerenone; Mineralocorticoids; Mineralocorticoid Receptor Antagonists
• Other Study ID Numbers: 2021P002400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes