Clinical trial NCT01395329: Nebivolol and the Endothelin (ET)-1 System
Official title: Nebivolol and the Endothelin (ET)-1 System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prehypertension
Hypertension
Lead sponsor: University of Colorado, Boulder
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
First posted: 2011-07-15
Enrollment: 42
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Systolic Blood Pressure
timeFrame: Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
measure: Diastolic Blood Pressure
timeFrame: Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
measure: Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min)
timeFrame: 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.
measure: Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min)
timeFrame: 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.
measure: FBF Response to Acetylcholine (ACh)
timeFrame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
measure: FBF Response to Sodium Nitroprusside
timeFrame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
measure: FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788)
timeFrame: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Secondary outcomes:
Other outcomes:
Locations:
city: Boulder
country: United States
facility: UC-Boulder Clinical and Translational Research Center
state: Colorado
Study officials:
affiliation: University of Colorado at Boulder
name: Christopher A DeSouza, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diehl KJ, Stauffer BL, Dow CA, Bammert TD, Brunjes DL, Greiner JJ, DeSouza CA. Chronic Nebivolol Treatment Suppresses Endothelin-1-Mediated Vasoconstrictor Tone in Adults With Elevated Blood Pressure. Hypertension. 2016 Jun;67(6):1196-204. doi: 10.1161/HYPERTENSIONAHA.115.06979. Epub 2016 Apr 25.