Prospective Phenotyping of Autonomous Aldosterone Secretion

Blood Pressure Clinical Trial

Official title:

Prospective Phenotyping of Autonomous Aldosterone Secretion: A Cohort Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03484130
• Other study ID #: 2018P000257
• Status: Active, not recruiting
• Start date: June 15, 2018
• Est. completion date: April 1, 2024

Study information

• Verified date: November 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Adrenal Gland Disease
• Adrenal Gland Diseases
• Aldosterone Disorder
• Blood Pressure

Intervention

Dietary Supplement:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in renin	The primary outcome is to evaluate the longitudinal change in plasma renin activity	5 years
Secondary	SASSI	The longitudinal change in the sodium modulated suppression-to-stimulation index	5 years
Secondary	Blood pressure	Longitudinal changes in blood pressure	5 years