PrehypertensionPhase 4NCT01595516
Nebivolol and Endothelial Regulation of Fibrinolysis (NERF)
A Phase 4 study testing Nebivolol, Metoprolol and Bradykinin in people with Prehypertension and Hypertension, run by University of Colorado, Boulder at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 45 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Prehypertension, Hypertension
- What is being tested?
- Nebivolol, Metoprolol and Bradykinin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Oct 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UC-Boulder Clinical and Translational Research Center
Boulder, Colorado, 80309
About this study
Official title: Nebivolol and Endothelial Regulation of Fibrinolysis
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.
- Conditions
- Prehypertension, Hypertension
- Being tested
- Nebivolol, Metoprolol, Placebo, Bradykinin, Saline
- Medical subject headings
- Prehypertension, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NebivololDrug
Also called Bystolic
5 mg tablet to be taken by mouth once per day for 12 weeks
MetoprololDrug
Also called Toprol-XL
100 mg tablet to be taken by mouth once per day for 12 weeks
PlaceboDrug
Gelatin capsule to be taken by mouth once per day for 12 weeks
BradykininOther
Also called BDK
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.
SalineOther
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 COther
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.
| Study group | Role | What they receive |
|---|---|---|
| Nebivolol | Active comparator | Not described Receives: Drug: Nebivolol |
| Metoprolol | Active comparator | Not described Receives: Drug: Metoprolol |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Bradykinin | Other | Not described Receives: Drug: Nebivolol; Drug: Metoprolol; Drug: Placebo; Other: Bradykinin |
| Saline | Other | Not described Receives: Drug: Nebivolol; Drug: Metoprolol; Drug: Placebo; Other: Bradykinin; Other: Saline; Other: Vitamin C |
| Vitamin C | Other | Not described Receives: Drug: Nebivolol; Drug: Metoprolol; Other: Bradykinin; Other: Saline; Other: Vitamin C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart Rate
Resting heart rate in the seated position
Measured: Heart rate was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Systolic Blood Pressure
Measured: Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
Diastolic Blood Pressure
Measured: Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
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.
Measured: t-PA release was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.
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.
Measured: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.
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.
Measured: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2012 (estimated)
- Study startFeb 2012
- Primary completionOct 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PrehypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Boulder
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Principal investigator, Christopher DeSouza, University of Colorado, Boulder
- Investigators
- Christopher DeSouza, Ph.D., Principal investigator, University of Colorado at Boulder
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01595516
- Sponsor's protocol ID
- BYS-MD-72
- Status last verified
- Jun 2019
- First submitted
- 5 Mar 2012
- Last updated
- 25 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Stauffer BL, Dow CA, Diehl KJ, Bammert TD, Greiner JJ, DeSouza CA. Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure. J Am Heart Assoc. 2017 Nov 9;6(11):e007437. doi: 10.1161/JAHA.117.007437.
PubMed 29122812
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nebivolol and Endothelial Regulation of Fibrinolysis
- ClinicalTrials.gov ID
- NCT01595516
- Acronym / sponsor ID
- BYS-MD-72
- Conditions
- Prehypertension, Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of Colorado, BoulderUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Feb 2012
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 10 May 2012 (estimated)
- Results
- Posted 25 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Nebivolol | Active comparator | Drug: Nebivolol |
| Metoprolol | Active comparator | Drug: Metoprolol |
| Placebo | Placebo comparator | Drug: Placebo |
| Bradykinin | Other | Drug: Nebivolol, Drug: Metoprolol, Drug: Placebo, Other: Bradykinin |
| Saline | Other | Drug: Nebivolol, Drug: Metoprolol, Drug: Placebo, Other: Bradykinin, Other: Saline, Other: Vitamin C |
| Vitamin C | Other | Drug: Nebivolol, Drug: Metoprolol, Other: Bradykinin, Other: Saline, Other: Vitamin C |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NebivololAlso: Bystolic5 mg tablet to be taken by mouth once per day for 12 weeks | Drug | Bradykinin, Nebivolol, Saline, Vitamin C |
| MetoprololAlso: Toprol-XL100 mg tablet to be taken by mouth once per day for 12 weeks | Drug | Bradykinin, Metoprolol, Saline, Vitamin C |
| PlaceboGelatin capsule to be taken by mouth once per day for 12 weeks | Drug | Bradykinin, Placebo, Saline |
| BradykininAlso: BDKBradykinin 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 | Bradykinin, Saline, Vitamin C |
| SalineBaseline 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. | Other | Saline, Vitamin C |
| Vitamin CThe 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. | Other | Saline, Vitamin C |
Primary outcome
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
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29122812Stauffer BL, Dow CA, Diehl KJ, Bammert TD, Greiner JJ, DeSouza CA. Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure. J Am Heart Assoc. 2017 Nov 9;6(11):e007437. doi: 10.1161/JAHA.117.007437.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher DeSouza, Ph.D. principal investigator
University of Colorado at Boulder
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nebivolol, Metoprolol and Bradykinin in people with Prehypertension and Hypertension, run by University of Colorado, Boulder at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01595516, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2019.