Skip to main content
OpenTrials
Completed

NCT Number: NCT01395329

Nebivolol and the Endothelin (ET)-1 System

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Prehypertension Cardiovascular Diseases Hypertension Vascular Diseases

Age range

45 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

UC-Boulder Clinical and Translational Research Center

Boulder, Colorado, 80309, United States

About this study

  • 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.
  • The investigators further hypothesize that reducing ET-1 vasoconstrictor activity contributes to the improvement in endothelial vasodilator function associated with nebivolol.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

nebivolol

Drug

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

Other names: Bystolic

metoprolol

Drug

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

Other names: Toprol-XL

Placebo

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)

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.

Other names: BQ-123

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

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.

Other names: BQ-123+BQ-788

FBF response to Acetylcholine

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.

Other names: ACh

FBF response to Sodium Nitroprusside

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.

Other names: NTP

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

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.

Other names: BQ-123+BQ-788+ACh

Primary outcomes

  1. Systolic Blood Pressure

    Time frame: Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

  2. Diastolic Blood Pressure

    Time frame: Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

  3. Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min)

    Time frame: 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.

    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.

  4. Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min)

    Time frame: 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.

    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.

  5. FBF Response to Acetylcholine (ACh)

    Time frame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

    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.

  6. FBF Response to Sodium Nitroprusside

    Time frame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

    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.

  7. FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788)

    Time frame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

    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.

Sponsors and collaborators

Lead sponsor

University of Colorado, Boulder

Other

Collaborators

  • Forest Laboratories

Registry information

Acronym: NETS

Important dates

Study start
2011
Primary completion
2016
Study completion
2016
First posted
Jul 15, 2011
Registry last updated
Jan 2, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.