Comparative Effect of Nebivolol vs. Metoprolol on Insulin Sensitivity and Fibrinolytic Balance in Metabolic Syndrome

Overview

Test the hypothesis that nebivolol treatment improves fibrinolytic balance and insulin sensitivity compared to metoprolol treatment in individuals with metabolic syndrome.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 2011

Detailed Description

1. Test the hypothesis that nebivolol treatment decreases PAI-1 antigen and activity and improves fibrinolytic balance compared to metoprolol treatment in individuals with metabolic syndrome. 2. Test the hypothesis that nebivolol treatment improves insulin sensitivity compared to metoprolol treatment in individuals with metabolic syndrome.

Interventions

  • Drug: placebo
    • Placebo pill by mouth daily for 21 days followed by either Nebivolol 5 mg by mouth daily or metoprolol ER 100mg by mouth daily for 12 weeks.
  • Drug: Nebivolol
    • Nebivolol 5 mg by mouth daily for 12 weeks.
  • Drug: Metoprolol
    • Metoprolol ER 100mg by mouth daily for 12 weeks.

Arms, Groups and Cohorts

  • Active Comparator: Nebivolol
    • Nebivolol 5mg by mouth daily for 12 weeks.
  • Active Comparator: Metoprolol
    • Metoprolol ER 100mg by mouth daily for 12 weeks.

Clinical Trial Outcome Measures

Primary Measures

  • Marker of Fibrinolysis
    • Time Frame: After 12 weeks of study drug
    • Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen.

Secondary Measures

  • Measurement of Insulin Sensitivity
    • Time Frame: 3 hours
    • The change in insulin sensitivity index, from baseline to after 12 weeks of treatment. Calculated from the intravenous glucose tolerance test at baseline and at 12 weeks.

Participating in This Clinical Trial

Inclusion Criteria

1. Ambulatory subjects, 18 to 70 years of age, inclusive 2. 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 prior to drug treatment and on every study day 3. Metabolic syndrome as defined by 3 or more of the following: – Fasting plasma glucose of at least 100 mg/dL (5.5 mmol/L) – Serum triglycerides of at least 150 mg/dL (1.7 mmol/L) – Serum HDL cholesterol less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL in women – Blood pressure of at least 130/85 mmHg – Waist girth of more than 102 cm in men or 88 cm in women Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study: 1. Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater or the use of anti-diabetic medication 2. Use of hormone replacement therapy 3. Change in statin therapy within the last 6 months 4. In hypertensive subjects, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg 5. Pregnancy 6. Breast-feeding 7. Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, 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 8. Treatment with anticoagulants 9. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack 10. History or presence of immunological or hematological disorders 11. Diagnosis of asthma 12. Clinically significant gastrointestinal impairment that could interfere with drug absorption 13. Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >2.0 x upper limit of normal range) 14. Impaired renal function (serum creatinine >1.5 mg/dl) 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 17. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) 18. Treatment with lithium salts 19. History of alcohol or drug abuse 20. Treatment with any investigational drug in the 1 month preceding the study 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 23. Inability to swallow capsules

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Vanderbilt University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Nancy J. Brown, Professor of Medicine and Pharmacology – Vanderbilt University
  • Overall Official(s)
    • Nancy J Brown, Principal Investigator, Vanderbilt University Medical Center

Citations Reporting on Results

Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Hypertension. 2012 Apr;59(4):893-8. doi: 10.1161/HYPERTENSIONAHA.111.189589. Epub 2012 Feb 21.

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