Hypertension, Pre-hypertension
Conditions
Keywords
Genetic risk of hypertension
Brief summary
The investigators aim to evaluate subjects at high risk of future development of hypertension, those with a family history of hypertension and/or that already have high normal(SBP 120-139 mmHg or DBP 80-89 mmHg) blood pressure. The investigators plan to investigate whether these subjects have the same markers (such as microscopic protein in the urine or C-reactive protein in the blood) in the blood and urine that people with high blood pressure have, and whether they are improved before and after taking the beta-blocker nebivolol.
Interventions
DRUGNebivolol
Oral nebivolol 2.5-5mg once daily
Sponsors
Forest Laboratories
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* • Prehypertensive male and female subjects with SBP =120-139 or DBP =80-89 with at least one known family member (must be diagnosed prior to the age of 60) with essential hypertension (confirmation may be sought). * All ethnicities * Non-smokers and non-drug abusers, no current smoking or illicit drug use in the prior 3 months. * Aged 18-40 years * No known serious medical conditions requiring close monitoring from physicians- such as liver impairment, chronic kidney disease, or diabetes mellitus * Subjects will need to remain in the San Diego area for the duration of the study (10 weeks) and be accessible by telephone or email. * Female subjects must be willing to use a birth control method, such as abstinence, birth control pills, diaphragm, condom, or intrauterine device to prevent pregnancy during the study.
Exclusion criteria
* Subjects with SBP \>140 or SBP\<120 or DBP \>90 and DBP\<80 * We will exclude subjects whose family members have known secondary etiologies for hypertension such as hyperaldosteronism or Cushing's Disease. * Subjects cannot have a chronic medical condition that is actively treated by a physician, such as liver impairment, diabetes, or kidney disease * History of bronchial asthma or chronic obstructive pulmonary disease * Subjects cannot be on any anti-hypertensive medications for any reason. * Subjects may not have previous intolerance, hypersensitivity, or allergy to any beta blocker therapy or may have contraindications to beta blocker therapy such as asthma, bradycardia, etc. * Subjects may not be taking medications which may affect the metabolism of nebivolol, such as those that inhibit CYP2D6 (such as fluoxetine or cimetidine) * Nursing women, pregnant women, or those that plan to become pregnant in the study period will also be excluded. (Pregnancy tests will be performed on all female subjects at the start of the study) * Subjects with pulse rate consistently \<60 beats per minute or evidence of arrythmias including atrioventricular block. * Those that have smoked or used illicit drugs within the past 3 months * Female subjects that are not willing to use a birth control method, such as abstinence, birth control pills, diaphragm, condom, or intrauterine device to prevent pregnancy during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Heart Rate, Beats Per a Minute | Basline (visit 1) and 8 weeks (visit 2) |
| Aortic Pulse Pressure | Basline (visit 1) and 8 weeks (visit 2) |
| Aortic Augmentation Pressure | Basline (visit 1) and 8 weeks (visit 2) |
| Aortic Augmentation Index for Heart Rate | Basline (visit 1) and 8 weeks (visit 2) |
| Pulse Wave Velocity | Basline (visit 1) and 8 weeks (visit 2) |
| Aortic Systolic Blood Pressure (SBP) | Basline (visit 1) and 8 weeks (visit 2) |
| Aortic Diastolic Blood Pressure (DBP) | Basline (visit 1) and 8 weeks (visit 2) |
| Aortic Mean Arterial Pressure (MAP) | Basline (visit 1) and 8 weeks (visit 2) |
Secondary
| Measure | Time frame |
|---|---|
| Urinary Isoprostane Excretion | Basline (visit 1) and 8 weeks (visit 2) |
| Urinary Hydrogen Peroxide Excretion | Baseline (visit 1) and 8 Weeks (visit 2) |
| Plasma Interleukin Levels | Basline (visit 1) and 8 weeks (visit 2) |
| Urinary Nitric Oxide Excretion | Basline (visit 1) and 8 weeks (visit 2) |
Countries
United States
Participant flow
Recruitment details
Study results are being entered according to a publication that was published before PI passed away. According to the publication; two participants dropped out because of flu-like symptoms, 2 were lost to follow-up, and 1 dropped out of the study after the initial visit but never took the medication. It is unknown what arm they were in.
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Nebivolol: Oral nebivolol 5 mg once daily | 25 |
| Placebo | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Nebivolol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 1.8 | 30.4 years STANDARD_DEVIATION 1.6 | 33.7 years STANDARD_DEVIATION 1.3 |
| Body Mass Index | 28.55 kg/m^2 STANDARD_DEVIATION 0.92 | 31.03 kg/m^2 STANDARD_DEVIATION 1.14 | 29.79 kg/m^2 STANDARD_DEVIATION 0.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 20 Participants |
| Sex: Female, Male Male | 18 Participants | 12 Participants | 30 Participants |
| Starting diastolic blood pressure | 84.7 mm Hg STANDARD_DEVIATION 1.5 | 84.4 mm Hg STANDARD_DEVIATION 1 | 84.5 mm Hg STANDARD_DEVIATION 0.9 |
| Starting systolic blood pressure | 127.4 mm Hg STANDARD_DEVIATION 1.6 | 126.2 mm Hg STANDARD_DEVIATION 1.5 | 126.8 mm Hg STANDARD_DEVIATION 1.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 50 |
| other Total, other adverse events | 1 / 50 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
Aortic Augmentation Index for Heart Rate
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Aortic Augmentation Index for Heart Rate | Baseline (visit 1) | 14.7 percentage | Standard Deviation 3.4 |
| Nebivolol | Aortic Augmentation Index for Heart Rate | Week 8 (visit 2) | 11.9 percentage | Standard Deviation 3.8 |
| Placebo | Aortic Augmentation Index for Heart Rate | Baseline (visit 1) | 14.5 percentage | Standard Deviation 2.4 |
| Placebo | Aortic Augmentation Index for Heart Rate | Week 8 (visit 2) | 12.8 percentage | Standard Deviation 2.9 |
Primary
Aortic Augmentation Pressure
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Aortic Augmentation Pressure | Baseline (visit 1) | 7.4 mm Hg | Standard Deviation 2 |
| Nebivolol | Aortic Augmentation Pressure | Week 8 (visit 2) | 6.8 mm Hg | Standard Deviation 1.6 |
| Placebo | Aortic Augmentation Pressure | Baseline (visit 1) | 5.5 mm Hg | Standard Deviation 1 |
| Placebo | Aortic Augmentation Pressure | Week 8 (visit 2) | 5.3 mm Hg | Standard Deviation 1.1 |
Primary
Aortic Diastolic Blood Pressure (DBP)
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Aortic Diastolic Blood Pressure (DBP) | Baseline (visit 1) | 79.1 mm Hg | Standard Deviation 2.3 |
| Nebivolol | Aortic Diastolic Blood Pressure (DBP) | Week 8 (visit 2) | 71.3 mm Hg | Standard Deviation 1.9 |
| Placebo | Aortic Diastolic Blood Pressure (DBP) | Baseline (visit 1) | 75.9 mm Hg | Standard Deviation 1.7 |
| Placebo | Aortic Diastolic Blood Pressure (DBP) | Week 8 (visit 2) | 74 mm Hg | Standard Deviation 1.8 |
Primary
Aortic Mean Arterial Pressure (MAP)
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Aortic Mean Arterial Pressure (MAP) | Baseline (visit 1) | 94.2 mm Hg | Standard Deviation 2.1 |
| Nebivolol | Aortic Mean Arterial Pressure (MAP) | Week 8 (visit 2) | 86.8 mm Hg | Standard Deviation 1.9 |
| Placebo | Aortic Mean Arterial Pressure (MAP) | Baseline (visit 1) | 90.4 mm Hg | Standard Deviation 1.6 |
| Placebo | Aortic Mean Arterial Pressure (MAP) | Week 8 (visit 2) | 88.6 mm Hg | Standard Deviation 1.9 |
Primary
Aortic Pulse Pressure
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Aortic Pulse Pressure | Baseline (visit 1) | 33.6 mm Hg | Standard Deviation 2.3 |
| Nebivolol | Aortic Pulse Pressure | Week 8 (visit 2) | 34.9 mm Hg | Standard Deviation 1.8 |
| Placebo | Aortic Pulse Pressure | Baseline (visit 1) | 31.8 mm Hg | Standard Deviation 1.4 |
| Placebo | Aortic Pulse Pressure | Week 8 (visit 2) | 32.6 mm Hg | Standard Deviation 1.2 |
Primary
Aortic Systolic Blood Pressure (SBP)
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Aortic Systolic Blood Pressure (SBP) | Baseline (visit 1) | 112.7 mm Hg | Standard Deviation 2.5 |
| Nebivolol | Aortic Systolic Blood Pressure (SBP) | Week 8 (visit 2) | 106.2 mm Hg | Standard Deviation 2.4 |
| Placebo | Aortic Systolic Blood Pressure (SBP) | Week 8 (visit 2) | 106.6 mm Hg | Standard Deviation 2 |
| Placebo | Aortic Systolic Blood Pressure (SBP) | Baseline (visit 1) | 107.7 mm Hg | Standard Deviation 1.9 |
Primary
Heart Rate, Beats Per a Minute
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Heart Rate, Beats Per a Minute | Week 8 (visit 2) | 64.4 beats per a minute | Standard Deviation 2.3 |
| Nebivolol | Heart Rate, Beats Per a Minute | Baseline (visit 1) | 72.0 beats per a minute | Standard Deviation 1.9 |
| Placebo | Heart Rate, Beats Per a Minute | Baseline (visit 1) | 75.6 beats per a minute | Standard Deviation 1.9 |
| Placebo | Heart Rate, Beats Per a Minute | Week 8 (visit 2) | 72.1 beats per a minute | Standard Deviation 2 |
Primary
Pulse Wave Velocity
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Pulse Wave Velocity | Baseline (visit 1) | 6.73 m/s | Standard Deviation 0.28 |
| Nebivolol | Pulse Wave Velocity | Week 8 (visit 2) | 6.00 m/s | Standard Deviation 0.18 |
| Placebo | Pulse Wave Velocity | Baseline (visit 1) | 5.95 m/s | Standard Deviation 0.19 |
| Placebo | Pulse Wave Velocity | Week 8 (visit 2) | 5.78 m/s | Standard Deviation 0.19 |
Secondary
Plasma Interleukin Levels
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Plasma Interleukin Levels | Baseline (visit 1) | 1.626 pg/ mL | Standard Deviation 0.598 |
| Nebivolol | Plasma Interleukin Levels | Week 8 (visit 2) | 1.647 pg/ mL | Standard Deviation 0.689 |
| Placebo | Plasma Interleukin Levels | Baseline (visit 1) | 1.351 pg/ mL | Standard Deviation 0.258 |
| Placebo | Plasma Interleukin Levels | Week 8 (visit 2) | 1.351 pg/ mL | Standard Deviation 0.258 |
Secondary
Urinary Hydrogen Peroxide Excretion
Time frame: Baseline (visit 1) and 8 Weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Urinary Hydrogen Peroxide Excretion | Baseline (visit 1) | 0.652 umol/ mg Cr | Standard Error 0.274 |
| Nebivolol | Urinary Hydrogen Peroxide Excretion | Week 8 (visit 2) | 2.79 umol/ mg Cr | Standard Error 1.83 |
| Placebo | Urinary Hydrogen Peroxide Excretion | Baseline (visit 1) | 0.500 umol/ mg Cr | Standard Error 0.281 |
| Placebo | Urinary Hydrogen Peroxide Excretion | Week 8 (visit 2) | 0.578 umol/ mg Cr | Standard Error 0.194 |
Secondary
Urinary Isoprostane Excretion
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Urinary Isoprostane Excretion | Baseline (visit 1) | 180 pg/ mg Cr | Standard Deviation 14 |
| Nebivolol | Urinary Isoprostane Excretion | Week 8 (visit 2) | 213 pg/ mg Cr | Standard Deviation 20 |
| Placebo | Urinary Isoprostane Excretion | Baseline (visit 1) | 165 pg/ mg Cr | Standard Deviation 17 |
| Placebo | Urinary Isoprostane Excretion | Week 8 (visit 2) | 185 pg/ mg Cr | Standard Deviation 22 |
Secondary
Urinary Nitric Oxide Excretion
Time frame: Basline (visit 1) and 8 weeks (visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Urinary Nitric Oxide Excretion | Baseline (visit 1) | 40.31 umol/ mg Cr | Standard Deviation 5.05 |
| Nebivolol | Urinary Nitric Oxide Excretion | Week 8 (visit 2) | 64.38 umol/ mg Cr | Standard Deviation 14.25 |
| Placebo | Urinary Nitric Oxide Excretion | Baseline (visit 1) | 61.77 umol/ mg Cr | Standard Deviation 11.86 |
| Placebo | Urinary Nitric Oxide Excretion | Week 8 (visit 2) | 65.54 umol/ mg Cr | Standard Deviation 10.54 |