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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.
 
ClinicalTrials.gov Identifier: NCT02362308
Recruitment Status : Active, not recruiting
First Posted : February 12, 2015
Last Update Posted : December 13, 2019
Sponsor:
Collaborators:
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

Tracking Information
First Submitted Date  ICMJE February 5, 2015
First Posted Date  ICMJE February 12, 2015
Last Update Posted Date December 13, 2019
Study Start Date  ICMJE January 2015
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2015)
  • Change in Acute Glucose-stimulated Insulin Secretion [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    measured by hyperglycemic clamp
  • Change in Insulin Sensitivity Index [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    measured by hyperinsulinemic-euglycemic clamp
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02362308 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2015)
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 11, 2015)
  • Urinary exosomal biomarkers [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    Urinary biomarkers of renal sodium channels and sodium transporters
  • Associative learning Memory testing [ Time Frame: Change from Baseline vs. 3-12 months after intervention ]
    Associative learning task matching images and words
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Glucose Metabolism in Subjects With Aldosterone-Producing Adenomas
Official Title  ICMJE Glucose Metabolism in Subjects With Aldosterone-Producing Adenomas
Brief Summary The investigators will test the hypothesis that endogenous aldosterone impairs insulin secretion and insulin sensitivity in subjects with primary aldosteronism.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Primary Aldosteronism
Intervention  ICMJE
  • Other: Adrenalectomy
    Adrenalectomy for treatment of primary aldosteronism, according to standard of care
  • Drug: mineralocorticoid receptor antagonist
    Subjects will be treated with a mineralocorticoid receptor antagonist according to standard of care
    Other Names:
    • spironolactone
    • eplerenone
Study Arms  ICMJE
  • Adrenalectomy
    Subjects will undergo assessment before and after adrenalectomy for treatment of primary aldosteronism
    Intervention: Other: Adrenalectomy
  • Medical Therapy
    Subjects will undergo assessment before and after medical treatment of primary aldosteronism
    Intervention: Drug: mineralocorticoid receptor antagonist
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 10, 2019)
10
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2015)
20
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02362308
Other Study ID Numbers  ICMJE 141553
R01DK096994 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party James Matt Luther, Vanderbilt University
Study Sponsor  ICMJE Vanderbilt University
Collaborators  ICMJE
  • Brigham and Women's Hospital
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: James M Luther, MD Vanderbilt University Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP