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

Metabolic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00775671
• Other study ID #: 080496
• Status: Completed
• Phase: Phase 4
• First received: October 17, 2008
• Last updated: September 23, 2012
• Start date: October 2008
• Est. completion date: June 2011

Study information

• Verified date: September 2012
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Ep — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Marker of Fibrinolysis	Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen.	After 12 weeks of study drug	No
Secondary	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	No