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Trial record 5 of 221 for:    Aldosterone

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
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Anand Vaidya, Brigham and Women's Hospital

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

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

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, 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.


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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

Drug Information available for: Aldosterone

Group/Cohort Intervention/treatment
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
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.

Drug: Para-Aminohippurate
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.




Primary Outcome Measures :
  1. Change in renin [ Time Frame: 5 years ]
    The primary outcome is to evaluate the longitudinal change in plasma renin activity


Secondary Outcome Measures :
  1. SASSI [ Time Frame: 5 years ]
    The longitudinal change in the sodium modulated suppression-to-stimulation index

  2. Blood pressure [ Time Frame: 5 years ]
    Longitudinal changes in blood pressure

  3. Renal Plasma Flow [ Time Frame: 5 years ]
    Longitudinal changes in renal plasma flow



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Normotensive individuals who have a reasonably high risk of developing hypertension in the next few years
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

Information from the National Library of Medicine

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


Contacts
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Contact: Anand Vaidya, MD, MMSc 6175258285 anandvaidya@bwh.harvard.edu
Contact: Kathleen Marion, NP 6177325186 kmarion@partners.org

Locations
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United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Anand Vaidya, MD, MMSc    617-525-8285    anandvaidya@bwh.harvard.edu   
Contact: Kathleen Marion, NP    6177325186    kmarion@partners.org   
Sponsors and Collaborators
Brigham and Women's Hospital
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Anand Vaidya, MD, MMSc Brigham and Women's Hospital

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Responsible Party: Anand Vaidya, Director, Center for Adrenal Disorders, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03484130     History of Changes
Other Study ID Numbers: 2018P000257
First Posted: March 30, 2018    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anand Vaidya, Brigham and Women's Hospital:
primary aldosteronism
Additional relevant MeSH terms:
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Adrenal Gland Diseases
Endocrine System Diseases
Angiotensin II
Giapreza
Angiotensinogen
Vasoconstrictor Agents
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action