Nebivolol and the Endothelin (ET)-1 System

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2016-12-31

Brief Summary

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The investigators hypothesize that nebivolol will reduce ET-1-mediated vasoconstrictor tone in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo.

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Detailed Description

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1. The investigators hypothesize that nebivolol will reduce ET-1-mediated vasoconstrictor tone in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo.
2. The investigators further hypothesize that reducing ET-1 vasoconstrictor activity contributes to the improvement in endothelial vasodilator function associated with nebivolol.

Conditions

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Prehypertension Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Nebivolol

Systolic and Diastolic blood pressure will be measured before and after randomization to12 weeks of Nebivolol. Forearm blood flow will be measured in response to 100 nmol/min of BQ-123, BQ-123+BQ788 (50 mol/min), Acetylcholine (4.0, 8.0, 16.0 ug/100 mL tissue/min), Sodium Nitroprusside (1.0, 2.0, 4.0 ug/100 mL tissue/min) and BQ-123+BQ-788+Acetylcholine (same doses as above) will be measured before and after the 12 weeks of nebivolol.

Group Type ACTIVE_COMPARATOR

Nebivolol

Intervention Type DRUG

5 mg tablet to be taken by mouth once per day for 12 weeks

Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min)

Intervention Type OTHER

The forearm blood flow response to the endothelin (ET) -1 A receptor blocker BQ-123 (100 nmol/min) for 60 minutes at baseline and at 12 weeks.

FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min)

Intervention Type OTHER

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

FBF response to Acetylcholine

Intervention Type OTHER

The FBF response to the endothelium-dependent vasodilator ACh (4, 8 and 16 ug/100 mL tissue/min) at baseline and at 12 weeks.

FBF response to Sodium Nitroprusside

Intervention Type OTHER

The FBF response to the endothelium independent vasodilator NTP (1,2 and 4 ug/100 mL tissue/min) at baseline and at 12 weeks.

FBF response to BQ-123+BQ-788+ACh

Intervention Type OTHER

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

Metoprolol

Systolic and Diastolic blood pressure will be measured before and after randomization to12 weeks of Metoprolol. Forearm blood flow will be measured in response to 100 nmol/min of BQ-123, BQ-123+BQ788 (50 mol/min), Acetylcholine (4.0, 8.0, 16.0 ug/100 mL tissue/min), Sodium Nitroprusside (1.0, 2.0, 4.0 ug/100 mL tissue/min) and BQ-123+BQ-788+Acetylcholine (same doses as above) will be measured before and after the 12 weeks of Metoprolol.

Group Type ACTIVE_COMPARATOR

Metoprolol

Intervention Type DRUG

100 mg tablet to be taken by mouth once per day for 12 weeks

Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min)

Intervention Type OTHER

The forearm blood flow response to the endothelin (ET) -1 A receptor blocker BQ-123 (100 nmol/min) for 60 minutes at baseline and at 12 weeks.

FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min)

Intervention Type OTHER

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

FBF response to Acetylcholine

Intervention Type OTHER

The FBF response to the endothelium-dependent vasodilator ACh (4, 8 and 16 ug/100 mL tissue/min) at baseline and at 12 weeks.

FBF response to Sodium Nitroprusside

Intervention Type OTHER

The FBF response to the endothelium independent vasodilator NTP (1,2 and 4 ug/100 mL tissue/min) at baseline and at 12 weeks.

FBF response to BQ-123+BQ-788+ACh

Intervention Type OTHER

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

Placebo

Systolic and Diastolic blood pressure will be measured before and after randomization to12 weeks of placebo. Forearm blood flow will be measured in response to 100 nmol/min of BQ-123, BQ-123+BQ788 (50 mol/min), Acetylcholine (4.0, 8.0, 16.0 ug/100 mL tissue/min), Sodium Nitroprusside (1.0, 2.0, 4.0 ug/100 mL tissue/min) and BQ-123+BQ-788+Acetylcholine (same doses as above) will be measured before and after the 12 weeks of placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

gelatin capsule to be taken by mouth once per day for 12 weeks

Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min)

Intervention Type OTHER

The forearm blood flow response to the endothelin (ET) -1 A receptor blocker BQ-123 (100 nmol/min) for 60 minutes at baseline and at 12 weeks.

FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min)

Intervention Type OTHER

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

FBF response to Acetylcholine

Intervention Type OTHER

The FBF response to the endothelium-dependent vasodilator ACh (4, 8 and 16 ug/100 mL tissue/min) at baseline and at 12 weeks.

FBF response to Sodium Nitroprusside

Intervention Type OTHER

The FBF response to the endothelium independent vasodilator NTP (1,2 and 4 ug/100 mL tissue/min) at baseline and at 12 weeks.

FBF response to BQ-123+BQ-788+ACh

Intervention Type OTHER

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

Interventions

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Nebivolol

5 mg tablet to be taken by mouth once per day for 12 weeks

Intervention Type DRUG

Metoprolol

100 mg tablet to be taken by mouth once per day for 12 weeks

Intervention Type DRUG

Placebo

gelatin capsule to be taken by mouth once per day for 12 weeks

Intervention Type DRUG

Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min)

The forearm blood flow response to the endothelin (ET) -1 A receptor blocker BQ-123 (100 nmol/min) for 60 minutes at baseline and at 12 weeks.

Intervention Type OTHER

FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min)

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

Intervention Type OTHER

FBF response to Acetylcholine

The FBF response to the endothelium-dependent vasodilator ACh (4, 8 and 16 ug/100 mL tissue/min) at baseline and at 12 weeks.

Intervention Type OTHER

FBF response to Sodium Nitroprusside

The FBF response to the endothelium independent vasodilator NTP (1,2 and 4 ug/100 mL tissue/min) at baseline and at 12 weeks.

Intervention Type OTHER

FBF response to BQ-123+BQ-788+ACh

The FBF response to the nonselective endothelin (ET) -1 receptor blockade BQ-123 (100 nmol/min) + BQ-788 (50 nmol/min)for 60 minutes at baseline and at 12 weeks.

Intervention Type OTHER

Other Intervention Names

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Bystolic Toprol-XL BQ-123 BQ-123+BQ-788 ACh NTP BQ-123+BQ-788+ACh

Eligibility Criteria

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Inclusion Criteria

* Subjects will be men and women of all races and ethnic backgrounds aged 45-65 years.
* Subjects will be prehypertensive/hypertensive defined as resting systolic blood pressure \>130 mmHg and \< 160 mm Hg and/or diastolic blood pressure \>80 mmHg and \< 100 mm Hg.
* All of the women in the study will be postmenopausal (at least 1 year from last menstrual cycle) and not receiving hormone replacement therapy (HRT) currently or in the preceding 3-year period.
* Lastly, candidates will be sedentary as determined from the Stanford Physical Activity Questionnaire (\<35 kcal/wk) and will not have engaged in any program of regular physical activity for at least 1 year prior to the study.

Exclusion Criteria

* Candidates who smoke (currently or in the past 7 years), report more than low-risk alcohol consumption as defined as no more than 14 standard drinks/wk and no more than 4 standard drinks/day for men and 7 standard drinks/wk and 3 standard drinks/day for women (a standard drink is defined as 12 ounces of beer, 5 ounces of wine, 1½ ounces of 80-proof distilled spirits)
* Potential candidates who are taking cardiovascular-acting (i.e. statins, blood pressure medication an aspirin) medications will not be eligible.
* Fasting plasma glucose \>126 mg/dL.
* Potential candidates with a resting heart rate of \< 50 beats/minute will be excluded.
* Use of hormone replacement therapy.
* In hypertensive subjects, a seated systolic blood pressure greater than 160 mmHg or a seated diastolic blood pressure greater than 100 mmHg.

Minimum Eligible Age

45 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes