Purpose

The investigators will test the hypothesis that endogenous aldosterone impairs insulin secretion and insulin sensitivity in subjects with primary aldosteronism.

Condition

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Ambulatory subjects, 18 to 70 years of age, inclusive
  2. For female subjects, the following conditions must be met:
  3. postmenopausal status for at least 1 year, or
  4. status-post surgical sterilization, or
  5. if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing on every study day.
  6. Primary aldosteronism determined by both:
  7. Biochemical hyperaldosteronism defined as either:
  8. Plasma aldosterone ≥15 ng/dL
  9. or aldosterone-to-renin ratio of ≥30 if on ACE inhibitor
  10. or aldosterone-to-renin ratio of ≥40 in absence of an ACE inhibitor
  11. Positive suppression test defined as either:
  12. failure to suppress aldosterone to <7ng/dL after intravenous 0.9% saline infusion over 2 hours
  13. failure to suppress 24-hour urinary aldosterone excretion to <12 µcg with simultaneously documented urine sodium excretion >200 mmol.

Exclusion Criteria

  • Subjects presenting with any of the following will not be included in the study:
  • Previously diagnosed type 1 Diabetes
  • Type II Diabetes, as defined by ADA criteria:
  • Hemoglobin A1C ≥6.5%
  • Fasting plasma glucose ≥126mg/dl (7.0mmol/l)
  • 2-hour 75g oral glucose tolerance test (OGTT) plasma glucose ≥200mg/dl (11.1 mmol/l) d. Current treatment with anti-diabetic medication(s)
  • Impaired renal function [estimated glomerular filtration rate (eGFR) of <30ml/min] as determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine (Scr) is expressed in mg/dl and age in years.
  • Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride, insulin), or to drugs within the same class.
  • Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
  • Cardiovascular disease such as recent (<6 months) myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
  • Breast-feeding
  • Treatment with anticoagulants
  • History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack
  • History or presence of immunological or hematological disorders
  • Diagnosis of asthma requiring use of inhaled beta agonist >1 time per week
  • Clinically significant gastrointestinal impairment that could interfere with drug absorption
  • Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) >2.0 x upper limit of normal range]
  • Hematocrit <35%
  • Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult, such as arthritis treated with non-steroidal antiinflammatory drugs
  • Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
  • Treatment with lithium salts
  • History of alcohol or drug abuse
  • Treatment with any investigational drug in the 1 month preceding the study
  • Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
  • Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Other
Adrenalectomy
Subjects will undergo assessment before and after adrenalectomy for treatment of primary aldosteronism
  • Other: Adrenalectomy
    Adrenalectomy for treatment of primary aldosteronism, according to standard of care
Other
Medical Therapy
Subjects will undergo assessment before and after medical treatment of primary aldosteronism
  • Drug: mineralocorticoid receptor antagonist
    Subjects will be treated with a mineralocorticoid receptor antagonist according to standard of care
    Other names:
    • spironolactone
    • eplerenone

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Loretta Byrne, RN
615-322-2105
loretta.byrne@vanderbilt.edu

More Details

NCT ID
NCT02362308
Status
Recruiting
Sponsor
Vanderbilt University

Study Contact

Loretta Byrne, RN
615-322-2105
loretta.byrne@vanderbilt.edu

Detailed Description

The week of each study period, subjects will be provided a standard 160mmol/d sodium diet for 6-8 days to control for inter-individual sodium intake.

In period 1, subjects will report after 5 days of controlled sodium diet for a hyperglycemic clamp study (to measure insulin secretion). Subjects will continue the study diet, and then return for a hyperinsulinemic-euglycemic clamp study (to measure insulin sensitivity).

After completion of period 1 assessment, subjects will undergo adrenalectomy by our endocrine surgeons or initiate medical treatment, according to routine clinical care.

In period 2, the investigators will repeat the studies in the same manner as period 1, 3 to 12 months after adrenalectomy or initiation of medical treatment.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.