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

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

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Drug: placebo; Drug: Nebivolol; Drug: Metoprolol

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nebivolol; Nebivolol 5mg by mouth daily for 12 weeks.	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.
Active Comparator: Metoprolol; Metoprolol ER 100mg by mouth daily for 12 weeks.	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: Metoprolol; Metoprolol ER 100mg by mouth daily for 12 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Nancy J Brown, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: October 17, 2008
• First Submitted That Met QC Criteria: October 17, 2008
• First Posted (Estimate): October 20, 2008

Study Record Updates

• Last Update Posted (Estimate): October 23, 2012
• Last Update Submitted That Met QC Criteria: September 23, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Hyperinsulinism; Syndrome; Metabolic Syndrome; Insulin Resistance; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-1 Receptor Agonists; Nebivolol; Metoprolol
• Other Study ID Numbers: 080496

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No