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

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

Detailed Description
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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. Test the hypothesis that nebivolol treatment improves insulin sensitivity compared to metoprolol treatment in individuals with metabolic syndrome.

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

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: placebo
* Drug: Nebivolol
* Drug: Metoprolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory subjects, 18 to 70 years of age, inclusive 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 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: 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 Use of hormone replacement therapy Change in statin therapy within the last 6 months In hypertensive subjects, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg Pregnancy Breast-feeding 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 Treatment with anticoagulants History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack History or presence of immunological or hematological disorders Diagnosis of asthma Clinically significant gastrointestinal impairment that could interfere with drug absorption Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >2.0 x upper limit of normal range) Impaired renal function (serum creatinine >1.5 mg/dl) Hematocrit <35% 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 Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) Treatment with lithium salts History of alcohol or drug abuse Treatment with any investigational drug in the 1 month preceding the study Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study Inability to swallow capsules

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nebivolol<br>Nebivolol 5mg by mouth daily for 12 weeks. | Drug: placebo<br>* 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.<br>Drug: Nebivolol<br>* Nebivolol 5 mg by mouth daily for 12 weeks.<br>|
| Active Comparator: Metoprolol<br>Metoprolol ER 100mg by mouth daily for 12 weeks. | Drug: placebo<br>* 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.<br>Drug: Metoprolol<br>* Metoprolol ER 100mg by mouth daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Marker of Fibrinolysis | Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen. | After 12 weeks of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Insulin Sensitivity | 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. | 3 hours |