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

Phase 4

Completed

• Conditions: Metabolic Syndrome
• Interventions: Drug: placebo; Drug: Nebivolol; Drug: Metoprolol

• Registration Number: NCT00775671
• Lead Sponsor: Vanderbilt University

Brief Summary

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

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 Timeline

• Study Start: 2008-10
• Study First Submitted: 2008-10-17
• Study First Submitted QC: 2008-10-17
• Study First Posted: 2008-10-20
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Status Verified: 2012-09
• Results First Submitted: 2012-09-23
• Results First Submitted QC: 2012-09-23
• Last Update Submitted: 2012-09-23
• Results First Posted: 2012-10-23
• Last Update Posted: 2012-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nebivolol	placebo	Nebivolol 5mg by mouth daily for 12 weeks.
Nebivolol	Nebivolol	Nebivolol 5mg by mouth daily for 12 weeks.
Metoprolol	placebo	Metoprolol ER 100mg by mouth daily for 12 weeks.
Metoprolol	Metoprolol	Metoprolol ER 100mg by mouth daily for 12 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Measurement of Insulin Sensitivity	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.

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States