Clinical trial NCT01103245: Aldosterone and the Metabolic Syndrome
Official title: Aldosterone and the Metabolic Syndrome: Renin Inhibition Versus Mineralocorticoid Receptor (MR) Antagonism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Keywords: Glucose
Insulin
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2010-04-14
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Detailed description: The purpose of this study is to determine the effects of mineralocorticoid receptor (MR) antagonism and renin inhibition on fasting blood glucose and glucose-stimulated insulin secretion 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

Primary outcomes:
measure: Plasma Insulin
timeFrame: at the end of each 1 month study period ( 3 times in total)
measure: Plasma Glucose
timeFrame: at the end of each 1 month study period ( 3 times in total)
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: James M Luther, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:38-44. doi: 10.1016/j.prostaglandins.2014.08.001. Epub 2014 Aug 28.