Nebivolol and Endothelial Regulation of Fibrinolysis (NERF)

Hypertension Clinical Trial

Official title:

Nebivolol and Endothelial Regulation of Fibrinolysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01595516
• Other study ID #: BYS-MD-72
• Status: Completed
• Phase: Phase 4
• Start date: February 2012
• Est. completion date: October 2017

Study information

• Verified date: June 2019
• Source: University of Colorado, Boulder
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• 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 >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.

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:
• Bradykinin
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.
• Saline
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
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.

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	Heart Rate	Resting heart rate in the seated position	Heart rate was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
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	Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week 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.	t-PA release was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Primary	Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.	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.	t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.
Primary	Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.	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.	t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.