Purpose

Aim 1.Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs glycemic control via effects on insulin sensitivity and insulin secretion. Aim 2. Test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system impairs insulin secretion and insulin sensitivity via an mineralocorticoid-receptor dependent mechanism.

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 prior to drug treatment and on every study day.
  6. Metabolic Syndrome as defined by the presence of > 3 of the following:
  7. Systolic Blood Pressure > 130 mm Hg OR Diastolic Blood Pressure > 85 mm Hg.
  8. Glucose Intolerance (Fasting Plasma Glucose ≥ 100 mg/dL)
  9. Increased triglyceride level > 150mg/dL (1.7mmol/L)
  10. Decreased levels of HDL cholesterol (For males, less than 40 mg/dL; For females, less than 50 mg/dL)
  11. Waist circumference (For males, greater than 40 inches; For females, greater than 35 inches)

Exclusion Criteria

  1. type 1 Diabetes
  2. Type II Diabetes
  3. Impaired renal function
  4. Prior allergies to medications used in the study protocol
  5. Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
  6. Cardiovascular disease
  7. Use of hormone replacement therapy
  8. Breast-feeding
  9. Treatment with anticoagulants
  10. History of serious neurologic disease
  11. History or presence of immunological or hematological disorders
  12. Diagnosis of asthma requiring use of inhaled beta agonist
  13. Clinically significant gastrointestinal impairment
  14. Impaired hepatic function
  15. Hematocrit <35%
  16. 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
  17. Treatment with chronic systemic glucocorticoid therapy
  18. Treatment with lithium salts
  19. History of alcohol or drug abuse
  20. Treatment with any investigational drug in the 1 month preceding
  21. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
  22. 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
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Basic Science
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Aim1-Low salt diet
Subjects will be provided with a diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
  • Other: glucose and insulin testing
Active Comparator
Aim 1-high salt diet
Subjects will be provided with a diet from the Vanderbilt Clinical Research Center that will be controlled for salt content.
  • Other: glucose and insulin testing
Active Comparator
Aim2- low salt diet and epleronone-amlodipine
Subjects on a low salt diet will receive epleronone 50mg for 8 days and assessments will be made, then cross over to a low salt diet with amlodipine 5mg for 8days and assessments will be made.
  • Other: glucose and insulin testing
Active Comparator
aim2- lowsaltdiet and amlodipine-epleronone
Subjects on a low salt diet will receive amlodipine 5mg for 8 days and assessments will be made, then cross over to a low salt diet with epleronone 50mg for 8days and assessments will be made.
  • Other: glucose and insulin testing

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232-6602
Contact:
Loretta Byrne, RN
615-322-2105
loretta.byrne@vanderbilt.edu

More Details

NCT ID
NCT02034435
Status
Recruiting
Sponsor
Vanderbilt University

Study Contact

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

Detailed Description

In aim 1 subjects are randomized to cross over between an 8 day high salt and 8 day low salt diet and assessments are made.

In aim 2, subjects are randomized to a 2x2 cross over study with an 8 day low salt diet and either eplerenone 50mg or amlodipine 5mg.

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.