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

NCT ID: NCT00775671

Last Updated: 2012-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2011-06-30

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.

Conditions

Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Nebivolol

Nebivolol 5mg by mouth daily for 12 weeks.

Group Type: ACTIVE_COMPARATOR

placebo

Intervention Type: DRUG

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.

Nebivolol

Intervention Type: DRUG

Nebivolol 5 mg by mouth daily for 12 weeks.

Metoprolol

Metoprolol ER 100mg by mouth daily for 12 weeks.

Group Type: ACTIVE_COMPARATOR

placebo

Intervention Type: DRUG

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.

Metoprolol

Intervention Type: DRUG

Metoprolol ER 100mg by mouth daily for 12 weeks.

Interventions

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.

Intervention Type: DRUG

Nebivolol

Nebivolol 5 mg by mouth daily for 12 weeks.

Intervention Type: DRUG

Metoprolol

Metoprolol ER 100mg by mouth daily for 12 weeks.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Nancy J. Brown

Professor of Medicine and Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nancy J Brown

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 22353614 (View on PubMed)

Other Identifiers

080496

Identifier Type: -

Identifier Source: org_study_id