Prospective Phenotyping of Autonomous Aldosterone Secretion
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|ClinicalTrials.gov Identifier: NCT03484130|
Recruitment Status : Recruiting
First Posted : March 30, 2018
Last Update Posted : July 2, 2019
|Condition or disease||Intervention/treatment|
|Aldosterone Disorder Adrenal Gland Disease Blood Pressure||Dietary Supplement: Sodium loaded diet Dietary Supplement: Restricted sodium diet Drug: Angiotensin II Drug: Para-Aminohippurate|
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, adrenal and vascular responses to angiotensin II, renal blood flow measurements, 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.
|Study Type :||Observational|
|Estimated Enrollment :||100 participants|
|Official Title:||Prospective Phenotyping of Autonomous Aldosterone Secretion: A Cohort Study|
|Actual Study Start Date :||June 15, 2018|
|Estimated Primary Completion Date :||April 1, 2023|
|Estimated Study Completion Date :||April 1, 2023|
These high-risk normotensives are considered to be enriched for subclinical autonomous aldosterone secretion and have a high risk for developing incident hypertension
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.
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.
Drug: Angiotensin II
At baseline, and annually, participants will undergo aldosterone dynamic testing after ~5 days of a sodium loaded diet. The dynamic testing will include a one hour infusion of angiotensin II (3 ng/kg/min) which will permit assessments of angiotensin II stimulated blood pressure, renal blood flow, and adrenal aldosterone secretion.
At baseline, and annually, participants will undergo aldosterone dynamic testing after ~5 days of a sodium loaded diet. This dynamic testing will include assessment of renal blood flow measured via para-aminohippurate clearance.
- Change in renin [ Time Frame: 5 years ]The primary outcome is to evaluate the longitudinal change in plasma renin activity
- SASSI [ Time Frame: 5 years ]The longitudinal change in the sodium modulated suppression-to-stimulation index
- Blood pressure [ Time Frame: 5 years ]Longitudinal changes in blood pressure
- Renal Plasma Flow [ Time Frame: 5 years ]Longitudinal changes in renal plasma flow
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03484130
|Contact: Anand Vaidya, MD, MMScemail@example.com|
|Contact: Kathleen Marion, NPfirstname.lastname@example.org|
|United States, Massachusetts|
|Brigham and Women's Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Anand Vaidya, MD, MMSc 617-525-8285 email@example.com|
|Contact: Kathleen Marion, NP 6177325186 firstname.lastname@example.org|
|Principal Investigator:||Anand Vaidya, MD, MMSc||Brigham and Women's Hospital|