Nebivolol and the Endothelin (ET)-1 System

Hypertension Clinical Trial

— NETS  

Official title:

Nebivolol and the Endothelin (ET)-1 System

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01395329
• Other study ID #: BYS-MD-57
• Status: Completed
• Phase: Phase 4
• Start date: May 2011
• Est. completion date: December 2016

Study information

• Verified date: December 2018
• Source: University of Colorado, Boulder
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: December 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Prehypertension

Intervention

Drug:
• Nebivolol
5 mg tablet to be taken by mouth once per day for 12 weeks
• Metoprolol
100 mg tablet to be taken by mouth once per day for 12 weeks
• Placebo
gelatin capsule to be taken by mouth once per day for 12 weeks

Other:
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	UC-Boulder Clinical and Translational Research Center	Boulder	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Boulder	Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systolic Blood Pressure		Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Primary	Diastolic Blood Pressure		Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Primary	Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min)	Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion.	Forearm blood flow was measured at 0-60 minutes before the 12 week drug or placebo intervention and 0-60 minutes after the 12 week drug or placebo intervention.
Primary	Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min)	Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion.	Forearm blood flow was measured 0-120 minutes before the 12 week drug or placebo intervention and 0-120 minutes after the 12 week drug or placebo intervention.
Primary	FBF Response to Acetylcholine (ACh)	FBF was measured via strain-gauge occlusion plethysmography at rest and in response to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported.	Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Primary	FBF Response to Sodium Nitroprusside	FBF was measured via strain-gauge occlusion plethysmography at rest and in response to sodium nitroprusside (1.0, 2.0 and 4.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported.	Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Primary	FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788)	FBF was measured via strain-gauge occlusion plethysmography at rest and in response to BQ-123+BQ-788 +ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported.	Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.