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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00775671
First received: October 17, 2008
Last updated: September 23, 2012
Last verified: September 2012
  Purpose

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


Condition Intervention Phase
Metabolic Syndrome
Drug: placebo
Drug: Nebivolol
Drug: Metoprolol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Comparative Effect of Nebivolol vs. Metoprolol on Insulin Sensitivity and Fibrinolytic Balance in Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Marker of Fibrinolysis [ Time Frame: After 12 weeks of study drug ] [ Designated as safety issue: No ]
    Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen.


Secondary Outcome Measures:
  • Measurement of Insulin Sensitivity [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    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.


Enrollment: 46
Study Start Date: October 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775671

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Nancy J Brown Vanderbilt University
  More Information

Publications:
Responsible Party: Nancy J. Brown, Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00775671     History of Changes
Other Study ID Numbers: 080496
Study First Received: October 17, 2008
Results First Received: September 23, 2012
Last Updated: September 23, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Syndrome
Metabolic Syndrome X
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Metoprolol
Nebivolol
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on September 18, 2014