Calcium Channel Blockade in Primary Aldosteronism (CCB-PA)

This pilot study explore whether the calcium channel blocker amlodipine can lower aldosterone levels in people with primary aldosteronism.

Study Overview

• Status: Completed
• Conditions: Primary Aldosteronism; Primary Aldosteronism Due to Adrenal Hyperplasia (Bilateral)
• Intervention / Treatment: Drug: Amlodipine

Detailed Description

BACKGROUND:

Primary aldosteronism is a common cause of hypertension. The cause of primary aldosteronism can be a unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) whereby there is diffuse production of ectopic and non-physiologic aldosterone in the adrenal cortex. IHA likely contributes to the majority of all primary aldosteronism. Whereas surgical cure is the preferred therapy for APA, lifelong mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone, are used to treat IHA. Treatment is important as patients with primary aldosteronism have an elevated risk of adverse cardiovascular and renal outcomes compared to patients with essential hypertension. It was long thought that curative surgery and lifelong medical therapy were equivalent treatment options, but more recent studies suggest that MRAs may not ameliorate the adverse cardiovascular and renovascular effects of primary aldosteronism to the same extent as surgery. For one, MRAs do not lower aldosterone levels, in fact, aldosterone levels are often increased with MRA therapy. Therefore, for IHA patients with primary aldosteronism in whom surgery is not an option, efforts to improve and optimize medical therapy are important.

Recent evidence in surgically removed adrenal glands from patients with primary aldosteronism and IHA has shown that even though IHA adrenal glands do not harbor adrenal tumors, they do harbor foci of ectopic aldosterone production and these foci are enriched for somatic mutations (gain of function) in CACNA1D, thereby suggesting that calcium channel mutations are predominant in the pathogenesis of IHA. This represents an intriguing target for medical therapy as blockade of this channel could lower intracellular calcium influx and hence decrease aldosterone production. Calcium channel blockade could also represent a more upstream therapy than mineralocorticoid receptor antagonists, which block the action of aldosterone at its receptor rather than lower its production.

This study is a pilot study to test the hypothesis that calcium channel blockade may lower autonomous aldosterone production in primary aldosteronism patients with IHA.

PROTOCOL:

Participants taking calcium channel blockers will be required to stop these medications for 2-4 weeks prior to initiation of the study. During this time, blood pressure will be managed with doxazosin and/or hydralazine to target an ideal range of <130/80 mmHg, but practically ranges of 120-150/60-90 mmHg will be allowed. Serum potassium will be treated with supplemental potassium chloride to target a range of 3.5-4.5 mEq/L prior to initiation of the study. Participants already on a mineralocorticoid receptor blocker must have a plasma renin activity of <1.0 ng/mL/h to participate, or be able to reduce or stop the dose of this medication for the duration of the study.

Study Visit 1: Participants will be provided sodium supplements (3g/daily) to take for five days prior to study visit 1. On the fifth day, a 24h urine collection will be obtained to measure urinary sodium and aldosterone and participants will arrive at the Clinical Research Center for testing. After one hour of seated rest, baseline blood measures will be obtained, and a single dose of amlodipine 10 mg will be administered. Blood measurements will be repeated every 2 hours to assess the serial change in outcome measures (t=2,4,and 6 hours after the amlodipine dose). Upon completion of the visit, participants will be prescribed amlodipine 10mg daily for 2 weeks.

Treatment phase: Following completion of Visit 1, participants will be prescribed amlodipine 10mg daily for 2 weeks. Home blood pressure monitoring will continue to ensure blood pressure remains in the target range of 120-150/80-90 mmHg. If blood pressure falls below this range with amlodipine, doxazosin and/or hydralazine doses may be reduced or stopped. If blood pressure remains low even after stopping doxazosin and hydralazine, the dose of amlodipine may be lowered to 5mg daily. Potassium chloride supplements may be titrated based on the values obtained at Study visit 1.

Study Visit 2: Participants will be provided sodium supplements (3g/daily) to take for five days prior to study visit 2. On the fifth day, a 24h urine collection will be obtained to measure urinary sodium and aldosterone and participants will arrive at the Clinical Research Center for testing. After one hour of seated rest, baseline blood measures will be obtained, and a single dose of amlodipine 10 mg will be administered. Blood measurements will be repeated every 2 hours to assess the serial change in outcome measures (t=2,4,and 6 hours after the amlodipine dose). Upon completion of the visit, the study will have concluded and participants will return to their usual care.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Anand Vaidya

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of primary aldosteronism
• Idiopathic bilateral hyperaldosteronism subtype based on adrenal venous sampling
• Primary aldosteronism treated with medical therapy (not surgery)
• Plasma renin activity <1.0 ng/mL/h

Exclusion Criteria:

• large or discrete adrenal adenoma on cross-sectional imaging
• inability to stop calcium channel blocker and transition to alternative medication
• inability to stop mineralocorticoid receptor antagonist and transition to alternative medication if plasma renin activity > 1.0 ng/mL/h
• Anemia
• leukopenia
• thrombocytopenia
• pregnant
• breastfeeding

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: Amlodipine; Amlodipine (dose 10 mg, once daily)	Drug: Amlodipine; Amlodipine (10mg daily, as tolerated by blood pressure parameters) for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24-hour Urinary Aldosterone Excretion Rate	Change in 24h urinary aldosterone excretion rate in response to maximal amlodipine therapy	Baseline and 2 weeks of amlodipine therapy
Change in Plasma Aldosterone Concentration	Change in plasma aldosterone concentration in response to maximal amlodipine therapy	Baseline and 2 weeks of amlodipine therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Change in Plasma Aldosterone Concentration	Change in plasma aldosterone concentration after a single dose of amlodipine, before and after 2 weeks of amlodipine therapy	Baseline plasma aldosterone concentration before amlodipine therapy and 6 hours post-amlodipine dose, compared to baseline plasma aldosterone after 2 weeks of amlodipine therapy and 6 hours post-amlodipine therapy.

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: University of Michigan
• Investigators: Principal Investigator: Anand Vaidya, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): December 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: November 24, 2019
• First Submitted That Met QC Criteria: November 24, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: primary aldosteronism; calcium channel blocker
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Gonadal Disorders; Congenital Abnormalities; Adrenal Gland Diseases; Disorders of Sex Development; Urogenital Abnormalities; Steroid Metabolism, Inborn Errors; Adrenocortical Hyperfunction; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Hyperaldosteronism; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Calcium Channel Blockers; Vasodilator Agents; Antihypertensive Agents; Amlodipine
• Other Study ID Numbers: 2019P003194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Requests to share the results of this small pilot study will be considered from clinical researchers with local institutional ethics approval. In these cases, IPD will be shared in a collaborative manner.
• IPD Sharing Time Frame: 1 year after the completion of the study
• IPD Sharing Access Criteria: clinical researchers with local institutional ethics approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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.: No