Aldosterone and the Metabolic Syndrome
Condition: Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders
MeSH terms: Metabolic Syndrome; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases
Intervention: Hydrochlorothiazide (HCTZ); Aliskiren 150 mg (ALI 150); Spironolactone (SPL 25); Aliskiren 300 mg (ALI 300); Spironolactone 50 mg (SPL 50)
Intervention description: HCTZ 12.5mg daily; Aliskiren 150mg daily; spironolactone 25mg daily; Aliskiren 300mg daily; Spironolactone 50 mg daily
Intervention MeSH terms: Hydrochlorothiazide; Spironolactone
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Glucose; Insulin

Summary:

      The purpose of this study is to determine the effects of mineralocorticoid receptor (MR)
      antagonism and renin inhibition on glucose metabolism in humans.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects meeting all of the following conditions will be included in the study:

               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. A seated or supine systolic blood pressure greater than 130/85 on three separate
                  measurements at least 15 minutes apart

               4. Metabolic Syndrome as defined by the presence of > 3 of the following:

                    1. Hypertension as characterized by having Systolic Blood Pressure > 140 mm Hg
                       and Diastolic Blood Pressure > 90 mm Hg.

                    2. Impaired Glucose Tolerance (Fasting Plasma Glucose > 100 mg/dL)

                    3. Increased triglyceride level > 150mg/dL

                    4. Decreased levels of High-Density Lipoprotein (HDL) cholesterol

                         1. For males, less than 30 mg/dL

                         2. For females, less than 40 mg/dL

                    5. Waist circumference

                         1. For males, greater than 40 inches.

                         2. For females, greater than 35 inches.

        Exclusion Criteria:

          -  Subjects presenting with any of the following will not be included in the study:

               1. Diabetes type 1 or type 2, a fasting glucose of greater than 110 mg/dL or the use
                  of anti-diabetic medication

               2. Use of hormone replacement therapy

               3. Statin therapy

               4. Pregnancy

               5. Breast-feeding

               6. Cardiovascular disease such as prior myocardial infarction, presence of angina
                  pectoris, significant arrhythmia, congestive heart failure [Left Ventricular (LV)
                  hypertrophy acceptable], deep vein thrombosis, pulmonary embolism, second or
                  third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic
                  cardiomyopathy

               7. Treatment with anticoagulants

               8. History of serious neurologic disease such as cerebral hemorrhage, stroke,
                  seizure, or transient ischemic attack

               9. History or presence of immunological or hematological disorders

              10. Diagnosis of asthma requiring use of inhaled beta agonist >1 time per week

              11. Clinically significant gastrointestinal impairment that could interfere with drug
                  absorption

              12. Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine
                  amino transaminase (ALT) >1.5 x upper limit of normal range]

              13. Impaired renal function [estimated glomerular filtration rate (eGFR) of
                  <60ml/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:

                  eGFR (ml/min/1.73m2)=175 • Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if
                  female)

              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

              22. Screening plasma potassium <3.2 mmol/L or use of chronic potassium supplements
                  for the treatment of hypokalemia