Nebivolol and the Endothelin (ET)-1 System (NETS)

University of Colorado Boulder (CU)

Status and phase: Completed; Phase 4

Conditions: Hypertension; Prehypertension

Treatments: Other: FBF response to Acetylcholine; Drug: Placebo; Other: Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min); Drug: Metoprolol; Other: FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min); Drug: Nebivolol; Other: FBF response to Sodium Nitroprusside; Other: FBF response to BQ-123+BQ-788+ACh

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01395329

BYS-MD-57

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 42 patients

Sex: All

Ages: 45 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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42 participants in 3 patient groups, including a placebo group

Nebivolol

Active Comparator group

Description:

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.

Treatment:

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

Other: FBF response to Sodium Nitroprusside

Drug: Nebivolol

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

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

Other: FBF response to Acetylcholine

Metoprolol

Active Comparator group

Description:

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.

Treatment:

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

Other: FBF response to Sodium Nitroprusside

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

Drug: Metoprolol

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

Other: FBF response to Acetylcholine

Placebo

Placebo Comparator group

Description:

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.

Treatment:

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

Other: FBF response to Sodium Nitroprusside

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

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

Other: FBF response to Acetylcholine

Drug: Placebo