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

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00775671
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome	Drug: placebo; Drug: Nebivolol; Drug: Metoprolol	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Comparative Effect of Nebivolol vs. Metoprolol on Insulin Sensitivity and Fibrinolytic Balance in Metabolic Syndrome
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. Marker of Fibrinolysis [After 12 weeks of study drug]

   Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen.

Secondary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

1. 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

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University

Investigators

• Principal Investigator: Nancy J Brown, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nancy J. Brown, Professor of Medicine and Pharmacology, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00775671
• Other Study ID Numbers: 080496
• First Posted: Oct 20, 2008
• Last Update Posted: Oct 23, 2012
• Last Verified: Sep 1, 2012

• Additional relevant MeSH terms: Metabolic Syndrome; Insulin Resistance; Syndrome; Metoprolol; Nebivolol

Study Results

Participant Flow

Recruitment Details	Participants answered recruitment advertisments. All qualifying participants had Metabolic Syndrome.
Pre-assignment Detail	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.

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Nebivolol 5mg by mouth daily for 12 weeks.	Metoprolol ER 100mg by motuh daily for 12 weeks.
Period Title: Overall Study
STARTED	23	23
COMPLETED	23	23
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Nebivolol	Metoprolol	Total
Arm/Group Description	Nebivolol 5mg by mouth daily for 12 weeks.	Metoprolol ER 100mg by motuh daily for 12 weeks.	Total of all reporting groups
Overall Participants	23	23	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	23 100%	46 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.3 (11.5)	47.4 (8.5)	44.4 (10.0)
Sex: Female, Male (Count of Participants)
Female	15 65.2%	15 65.2%	30 65.2%
Male	8 34.8%	8 34.8%	16 34.8%
Region of Enrollment (participants) [Number]
United States	23 100%	23 100%	46 100%

Outcome Measures

1. Secondary Outcome

Title	Measurement of Insulin Sensitivity
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Nebivolol 5mg by mouth daily for 12 weeks.	Metoprolol ER 100mg by motuh daily for 12 weeks.
Measure Participants	23	23
Mean (Standard Deviation) [10-4xmin-1 per mU/L]	0.04 (2.19)	-1.5 (2.5)

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Nebivolol 5mg by mouth daily for 12 weeks.	Metoprolol ER 100mg by motuh daily for 12 weeks.
Measure Participants	23	23
Mean (Standard Deviation) [ng/mL]	10.5 (6.2)	12.3 (7.8)

Adverse Events

Time Frame	18 weeks
Adverse Event Reporting Description	Time from washing off antihypertensive medication, taking placebo for 21 days, and taking study drug for 12 weeks.
Arm/Group Title	Nebivolol		Metoprolol
Arm/Group Description	Nebivolol 5mg by mouth daily for 12 weeks.		Metoprolol ER 100mg by motuh daily for 12 weeks.
All Cause Mortality
	Nebivolol		Metoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nebivolol		Metoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Nebivolol		Metoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/23 (60.9%)		7/23 (30.4%)
General disorders
Headache	3/23 (13%)	3	1/23 (4.3%)	1
Sore Throat	2/23 (8.7%)	2	0/23 (0%)	0
palpitations	0/23 (0%)	0	2/23 (8.7%)	2
Renal and urinary disorders
urinary tract infection	0/23 (0%)	0	2/23 (8.7%)	2
Respiratory, thoracic and mediastinal disorders
congestion	9/23 (39.1%)	9	2/23 (8.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.