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Trial record 64 of 228 for:    EDN1

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

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ClinicalTrials.gov Identifier: NCT01395329
Recruitment Status : Completed
First Posted : July 15, 2011
Results First Posted : December 6, 2018
Last Update Posted : January 1, 2019
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Christopher DeSouza, University of Colorado, Boulder

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.

Condition or disease Intervention/treatment Phase
Prehypertension Hypertension Drug: Nebivolol Drug: Metoprolol Drug: Placebo Other: Forearm Blood Flow (FBF) response to BQ-123 (100 mol/min) Other: FBF response to BQ-123 (100 nmol/min)+BQ-788(50 nmol/min) Other: FBF response to Acetylcholine Other: FBF response to Sodium Nitroprusside Other: FBF response to BQ-123+BQ-788+ACh Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Nebivolol and the Endothelin (ET)-1 System
Study Start Date : May 2011
Actual Primary Completion Date : November 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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.
Drug: Nebivolol
5 mg tablet to be taken by mouth once per day for 12 weeks
Other Name: Bystolic

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.
Other Name: BQ-123

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.
Other Name: BQ-123+BQ-788

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.
Other Name: ACh

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.
Other Name: NTP

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.
Other Name: BQ-123+BQ-788+ACh

Active Comparator: 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.
Drug: Metoprolol
100 mg tablet to be taken by mouth once per day for 12 weeks
Other Name: Toprol-XL

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.
Other Name: BQ-123

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.
Other Name: BQ-123+BQ-788

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.
Other Name: ACh

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.
Other Name: NTP

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.
Other Name: BQ-123+BQ-788+ACh

Placebo Comparator: 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.
Drug: 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.
Other Name: BQ-123

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.
Other Name: BQ-123+BQ-788

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.
Other Name: ACh

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.
Other Name: NTP

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.
Other Name: BQ-123+BQ-788+ACh




Primary Outcome Measures :
  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01395329


Locations
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United States, Colorado
UC-Boulder Clinical and Translational Research Center
Boulder, Colorado, United States, 80309
Sponsors and Collaborators
University of Colorado, Boulder
Forest Laboratories
Investigators
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Principal Investigator: Christopher A DeSouza, Ph.D. University of Colorado at Boulder

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Christopher DeSouza, Professor, University of Colorado, Boulder
ClinicalTrials.gov Identifier: NCT01395329     History of Changes
Other Study ID Numbers: BYS-MD-57
First Posted: July 15, 2011    Key Record Dates
Results First Posted: December 6, 2018
Last Update Posted: January 1, 2019
Last Verified: December 2018
Additional relevant MeSH terms:
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Prehypertension
Vascular Diseases
Cardiovascular Diseases
Metoprolol
Nebivolol
Nitroprusside
cyclo(Trp-Asp-Pro-Val-Leu)
BQ 788
Acetylcholine
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Cholinergic Agonists
Cholinergic Agents
Nitric Oxide Donors
Endothelin Receptor Antagonists
Endothelin B Receptor Antagonists