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Glucose Metabolism in Subjects With Aldosterone-Producing Adenomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02362308
Recruitment Status : Completed
First Posted : February 12, 2015
Last Update Posted : May 4, 2021
Brigham and Women's Hospital
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
James Matt Luther, Vanderbilt University

Brief Summary:
This observational study tests the hypothesis that endogenous aldosterone impairs insulin secretion and insulin sensitivity in subjects with primary aldosteronism.

Condition or disease Intervention/treatment
Primary Aldosteronism Other: Adrenalectomy Drug: mineralocorticoid receptor antagonist

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.

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Study Type : Observational
Actual Enrollment : 10 participants
Official Title: Glucose Metabolism in Subjects With Aldosterone-Producing Adenomas
Actual Study Start Date : January 2015
Actual Primary Completion Date : January 2020
Actual Study Completion Date : January 2020

Group/Cohort Intervention/treatment
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

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

Primary Outcome Measures :
  1. Change in Acute Glucose-stimulated Insulin Secretion [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    measured by hyperglycemic clamp

  2. Change in Insulin Sensitivity Index [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    measured by hyperinsulinemic-euglycemic clamp

  3. Change in Disposition Index (product of Insulin sensitivity index and acute insulin secretion) [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    Product of insulin sensitivity and insulin secretion

Secondary Outcome Measures :
  1. Suppression of Hepatic glucose production [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    suppression of hepatic glucose production during hyperinsulinemic clamp, determined using glucose tracer

Other Outcome Measures:
  1. Urinary exosomal biomarkers [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    Urinary biomarkers of renal sodium channels and sodium transporters

  2. Associative learning Memory testing [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    Associative learning task matching images and words

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   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:

    • postmenopausal status for at least 1 year, or
    • status-post surgical sterilization, or
    • if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing on every study day.
  3. Primary aldosteronism determined by both:

    • Biochemical hyperaldosteronism defined as either:

      1. Plasma aldosterone ≥15 ng/dL
      2. or aldosterone-to-renin ratio of ≥30 if on ACE inhibitor
      3. or aldosterone-to-renin ratio of ≥40 in absence of an ACE inhibitor
    • Positive suppression test defined as either:

      1. failure to suppress aldosterone to <7ng/dL after intravenous 0.9% saline infusion over 2 hours
      2. 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:

  1. Previously diagnosed type 1 Diabetes
  2. 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)
  3. 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.
  4. Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride, insulin), or to drugs within the same class.
  5. Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
  6. 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
  7. Breast-feeding
  8. Treatment with anticoagulants
  9. History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack
  10. History or presence of immunological or hematological disorders
  11. Diagnosis of asthma requiring use of inhaled beta agonist >1 time per week
  12. Clinically significant gastrointestinal impairment that could interfere with drug absorption
  13. Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) >2.0 x upper limit of normal range]
  14. Hematocrit <35%
  15. 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
  16. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
  17. Treatment with lithium salts
  18. History of alcohol or drug abuse
  19. Treatment with any investigational drug in the 1 month preceding the study
  20. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
  21. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

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 identifier (NCT number): NCT02362308

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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Brigham and Women's Hospital
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: James M Luther, MD Vanderbilt University Medical Center
Publications of Results:
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Responsible Party: James Matt Luther, James M Luther MD, MSCI, Vanderbilt University Identifier: NCT02362308    
Other Study ID Numbers: 141553
R01DK096994 ( U.S. NIH Grant/Contract )
First Posted: February 12, 2015    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: April 2021
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents
Antihypertensive Agents