Prospective Phenotyping of Autonomous Aldosterone Secretion

NCT ID: NCT03484130

Last Updated: 2025-10-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-06-15
• Study Completion Date: 2029-07-01

Brief Summary

This prospective cohort study will investigate the physiology and progression of autonomous aldosterone secretion.

Detailed Description

Primary aldosteronism is a disorder wherein aldosterone is secreted by the adrenal gland(s) independent of its physiologic regulators and cannot be appropriately suppressed with sodium/volume loading. Primary aldosteronism is a common cause of hypertension and has a relatively high prevalence. This is important since the excessive mineralocorticoid receptor activation in primary aldosteronism contributes to adverse cardiovascular and renal outcomes and death. For these reasons, it is critical that autonomous aldosteronism be detected early in its course since appropriate treatment interventions may prevent cardiovascular disease.

In addition to severe and overt primary aldosteronism in hypertension, human studies have shown that milder forms of primary aldosteronism can exist even among normotensive individuals. Detailed physiologic studies have shown that normotensive individuals with a phenotype of autonomous aldosterone secretion have greater cardiometabolic risk factors, impaired renal-vascular function, and a higher risk for developing incident hypertension. Further, older age is associated with greater autonomous aldosterone secretion, suggesting that autonomous aldosterone secretion may progress over time. A better understanding of the prevalence and progression of this type of "subclinical" autonomous aldosterone secretion may inform our understanding of the pathogenesis of hypertension and cardiometabolic diseases.

This protocol is designed to be a prospective longitudinal study that will carefully characterize the degree of autonomous aldosterone secretion among high-risk normotensive individuals and follow them longitudinally with repeated phenotyping study visits to assess the progression and severity of autonomous aldosterone secretion over time and its relevance to cardiovascular health. Phenotyping visits will include measurements of the renin-angiotensin-aldosterone system under controlled posture and variable sodium intakes and repeated assessments of blood pressure.

This prospective cohort study will provide insights into normal and abnormal aldosterone physiology over time and how it may contribute to time- or age-dependent hypertension and cardiometabolic risk.

Conditions

Aldosterone Disorder; Adrenal Gland Disease; Blood Pressure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

High-Risk Normotensives

These high-risk normotensives are considered to be enriched for subclinical autonomous aldosterone secretion and have a high risk for developing incident hypertension

Sodium loaded diet

Intervention Type: DIETARY_SUPPLEMENT

At baseline, and annually, participants will undergo aldosterone dynamic testing after \~5 days of a sodium loaded diet. The diet will consist of \>180 mmol/day of sodium, \~50 mmol/day of potassium, and 600mg/d of calcium.

Restricted sodium diet

Intervention Type: DIETARY_SUPPLEMENT

At baseline, and annually, participants will undergo aldosterone dynamic testing after \~5 days of a sodium restricted diet. The diet will consist of \<40 mmol/day of sodium, \~50 mmol/day of potassium, and 600mg/d of calcium.

Interventions

Sodium loaded diet

At baseline, and annually, participants will undergo aldosterone dynamic testing after \~5 days of a sodium loaded diet. The diet will consist of \>180 mmol/day of sodium, \~50 mmol/day of potassium, and 600mg/d of calcium.

Intervention Type: DIETARY_SUPPLEMENT

Restricted sodium diet

At baseline, and annually, participants will undergo aldosterone dynamic testing after \~5 days of a sodium restricted diet. The diet will consist of \<40 mmol/day of sodium, \~50 mmol/day of potassium, and 600mg/d of calcium.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. Age 35-70 years

2. Systolic blood pressure of 120-135 mmHg and/or diastolic blood pressure of 75-85 mmHg

3. At least one, or more, of the following:

• BMI ≥ 25 kg/m2
• Family history of hypertension prior to the age of 60 years in a parent or sibling
• Diabetes with a hemoglobin A1c < 9%

4. If systolic blood pressure 115-135 mmHg and/or diastolic blood pressure 70-85 mmHg, must have two or more of the following:

• BMI ≥ 25 kg/m2
• Family history of hypertension prior to the age of 60 years in a parent or sibling
• Diabetes with a hemoglobin A1c < 9%

Exclusion Criteria

• Known history of hypertension or use of antihypertensive medications
• Known history of stroke, coronary artery disease, myocardial infarction, heart failure, cerebral or aortic aneurysm, or preeclampsia.
• Active cancer that is being treated with chemotherapeutic agents
• Pregnancy
• Breast feeding
• Daily use of prescribed opioid medications
• Illicit drug use (cocaine, heroin, methamphetamine)
• Daily non-steroidal anti-inflammatory medication use
• Daily use of glucocorticoids
• Electrocardiogram that shows evidence of prior myocardial infarction, atrial arrhythmia, left or right bundle branch blocks.
• Estimated glomerular filtration rate < 60 mL/min/1.73m2
• Active and untreated hyper- or hypo-thyroidism
• Abnormal screening laboratories (comprehensive metabolic panel, complete blood count, thyrotropin)
• BMI ≥ 45 kg/m2

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Anand Vaidya

Director, Center for Adrenal Disorders

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anand Vaidya, MD, MMSc

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2018P000257

Identifier Type: -

Identifier Source: org_study_id