Glucose Metabolism in Subjects With Aldosterone-Producing Adenomas

NCT02362308 | Completed DMC

• 2 other identifiers: 141553R01DK096994
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Primary Aldosteronism

Outcome Measures

Primary Outcomes (3)

• Change in Acute Glucose-stimulated Insulin Secretion

  measured by hyperglycemic clamp

  Change from Baseline vs. 3-12 months after intervention

• Change in Insulin Sensitivity Index

  measured by hyperinsulinemic-euglycemic clamp

  Change from Baseline vs. 3-12 months after intervention

• Change in Disposition Index (product of Insulin sensitivity index and acute insulin secretion)

  Product of insulin sensitivity and insulin secretion

  Change from Baseline vs. 3-12 months after intervention

Secondary Outcomes (1)

• Suppression of Hepatic glucose production

  Change from Baseline vs. 3-12 months after intervention

Other Outcomes (2)

• Urinary exosomal biomarkers

  Change from Baseline vs. 3-12 months after intervention

• Associative learning Memory testing

  Change from Baseline vs. 3-12 months after intervention

Study Arms (2)

Adrenalectomy

Subjects will undergo assessment before and after adrenalectomy for treatment of primary aldosteronism

Other: Adrenalectomy

Medical Therapy

Subjects will undergo assessment before and after medical treatment of primary aldosteronism

Drug: mineralocorticoid receptor antagonist

Interventions

Adrenalectomy OTHER

Adrenalectomy for treatment of primary aldosteronism, according to standard of care

Adrenalectomy

mineralocorticoid receptor antagonist DRUG

Subjects will be treated with a mineralocorticoid receptor antagonist according to standard of care

Also known as: spironolactone, eplerenone

Medical Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory subjects, 18 to 70 years of age, inclusive
• 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.
• Primary aldosteronism determined by both:
• Biochemical hyperaldosteronism defined as either:
• Plasma aldosterone ≥15 ng/dL
• or aldosterone-to-renin ratio of ≥30 if on ACE inhibitor
• or aldosterone-to-renin ratio of ≥40 in absence of an ACE inhibitor
• Positive suppression test defined as either:
• failure to suppress aldosterone to \<7ng/dL after intravenous 0.9% saline infusion over 2 hours
• failure to suppress 24-hour urinary aldosterone excretion to \<12 µcg with simultaneously documented urine sodium excretion \>200 mmol.

You may not qualify if:

• \- 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)
• 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

Sponsors & Collaborators

• Vanderbilt University: lead
• Brigham and Women's Hospital: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

• Luther JM, Wei DS, Ghoshal K, Peng D, Adler GK, Turcu AF, Nian H, Yu C, Solorzano CC, Pozzi A, Brown NJ. Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids. Hypertension. 2021 Apr;77(4):1323-1331. doi: 10.1161/HYPERTENSIONAHA.120.14808. Epub 2021 Feb 15.

  PMID: 33583202 RESULT

• Adler GK, Murray GR, Turcu AF, Nian H, Yu C, Solorzano CC, Manning R, Peng D, Luther JM. Primary Aldosteronism Decreases Insulin Secretion and Increases Insulin Clearance in Humans. Hypertension. 2020 May;75(5):1251-1259. doi: 10.1161/HYPERTENSIONAHA.119.13922. Epub 2020 Mar 16.

  PMID: 32172621 RESULT

MeSH Terms

Conditions

Hyperaldosteronism

Interventions

Adrenalectomy; Mineralocorticoid Receptor Antagonists; Spironolactone; Eplerenone

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Endocrine Surgical Procedures; Surgical Procedures, Operative; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• James M Luther, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: James M Luther MD, MSCI

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 12, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: May 4, 2021

Record last verified: 2021-04

Locations

US (1)