Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome
Intervention: Low Salt diet plus Placebo tablet; Low Sodium diet plus Salt tablet; Epleronone; Amlodipine
Intervention description: 50mg daily; 5mg daily
Intervention MeSH terms: Amlodipine
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Ambulatory subjects, 18 to 70 years of age, inclusive

          2. For female subjects, the following conditions must be met:

               1. postmenopausal status for at least 1 year, or

               2. status-post surgical sterilization, or

               3. 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.

          3. Metabolic Syndrome as defined by the presence of > 3 of the following:

               1. Systolic Blood Pressure > 130 mm Hg OR Diastolic Blood Pressure > 85 mm Hg.

               2. Glucose Intolerance (Fasting Plasma Glucose ≥ 100 mg/dL)

               3. Increased triglyceride level > 150mg/dL (1.7mmol/L)

               4. Decreased levels of HDL cholesterol (For males, less than 40 mg/dL; For females,
                  less than 50 mg/dL)

               5. 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