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Completed

NCT Number: NCT01595516

Nebivolol and Endothelial Regulation of Fibrinolysis (NERF)

The investigators hypothesize that nebivolol will improve endothelial t-PA release in adult humans with elevated blood pressure to a greater extent than either metoprolol or placebo. The investigators further hypothesize that the improvement in the capacity of the vascular endothelium to release t-PA with nebivolol is mediated, in part, by the compound's antioxidant properties.

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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

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 >125 mmHg and <160 mmHg and/or diastolic >80 mmHg and <100 mmHg.
  • All of the women in the study will be postmenopausal and not receiving hormone replacement therapy (HRT) currently or in the preceding 3-year period.
  • 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 and 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 >160 mmHg or a seated diastolic blood pressure >100 mmHg will be excluded.

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

Bradykinin

Other

Bradykinin is infused into the brachial artery at doses of 12.5, 25.0 and 50.0 ng/100 mL of forearm tissue /min. BDK stimulates the endothelial cells to release tissue type plasminogen activator (t-PA). Blood flow in mL/100 mL tissue/min is also measured to BDK.

Other names: BDK

Saline

Other

Baseline or resting forearm blood flow is measured in response to saline for 5 minutes before each drug infusion. t-PA release in response to the saline is also measured.

Vitamin C

Other

The acute effects of into-arterial vitamin C on the ability of the endothelium to release t-PA was determined before and after the nebivolol and metoprolol intervention. After allowing sufficient time (~20 minutes) for FBF and plasma t-PA concentrations to return to baseline following the initial infusion of BDK, vitamin C (24 mg/min) was infused at a constant rate while the BDK dose-response curves were repeated. t-PA and FBF were measured.

Primary outcomes

  1. Heart Rate

    Time frame: Heart rate was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

    Resting heart rate in the seated position

  2. 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.

  3. 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.

  4. Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention

    Time frame: t-PA release was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

    Net endothelial release of t-PA antigen in response to bradykinin (BDK) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK). t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.

  5. Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.

    Time frame: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.

    Net endothelial release of t-PA antigen in response to bradykinin (BDK) and bradykinin+vitamin C (BDK+C) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.

  6. Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.

    Time frame: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.

    Net endothelial release of t-PA antigen in response to BDK and BDK+C was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells.

Sponsors and collaborators

Lead sponsor

University of Colorado, Boulder

Other

Collaborators

  • Forest Laboratories

Registry information

Official study title

Nebivolol and Endothelial Regulation of Fibrinolysis

Important dates

Study start
2012
Primary completion
2017
Study completion
2017
First posted
May 10, 2012
Registry last updated
Jun 25, 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.

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