Metabolic Syndrome
Conditions
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.
Interventions
DRUGplacebo
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.
DRUGNebivolol
Nebivolol 5 mg by mouth daily for 12 weeks.
DRUGMetoprolol
Metoprolol ER 100mg by mouth daily for 12 weeks.
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Marker of Fibrinolysis | After 12 weeks of study drug | Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants answered recruitment advertisments. All qualifying participants had Metabolic Syndrome.
Pre-assignment details
Participants that met inclusion criteria stopped their antihypertensive medications for 3 weeks before study start. All participants took a placebo pill daily for 21 days and had baseline measurements done.
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Nebivolol 5mg by mouth daily for 12 weeks. | 23 |
| Metoprolol Metoprolol ER 100mg by motuh daily for 12 weeks. | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Metoprolol | Nebivolol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Age Continuous | 47.4 years STANDARD_DEVIATION 8.5 | 41.3 years STANDARD_DEVIATION 11.5 | 44.4 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 23 participants | 23 participants | 46 participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 23 | 7 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Marker of Fibrinolysis
Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen.
Time frame: After 12 weeks of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol | Marker of Fibrinolysis | 10.5 ng/mL | Standard Deviation 6.2 |
| Metoprolol | Marker of Fibrinolysis | 12.3 ng/mL | Standard Deviation 7.8 |
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.
Time frame: 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol | Measurement of Insulin Sensitivity | 0.04 10-4xmin-1 per mU/L | Standard Deviation 2.19 |
| Metoprolol | Measurement of Insulin Sensitivity | -1.5 10-4xmin-1 per mU/L | Standard Deviation 2.5 |