Effects of the Beta-blocker Nebivolol (Bystolic) on Subjects With High Normal Blood Pressure and/or a Family History of Hypertension

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT01202175
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 50
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pre-hypertension; Hypertension	Drug: Nebivolol	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Effects of the Novel Beta-adrenergic Antagonist Nebivolol (Bystolic) on Prehypertensive Subjects at Genetic Risk of Hypertension: Implications for Inflammation, Endothelial Dysfunction, and Oxidative Stress.
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nebivolol	Drug: Nebivolol; Oral nebivolol 2.5-5mg once daily; Other Names: Bystolic
Placebo Comparator: Sugar pill	Drug: Nebivolol; Oral nebivolol 2.5-5mg once daily; Other Names: Bystolic

Outcome Measures

Primary Outcome Measures

1. Aortic Systolic Blood Pressure (SBP) [Basline (visit 1) and 8 weeks (visit 2)]

2. Aortic Diastolic Blood Pressure (DBP) [Basline (visit 1) and 8 weeks (visit 2)]

3. Aortic Mean Arterial Pressure (MAP) [Basline (visit 1) and 8 weeks (visit 2)]

4. Aortic Pulse Pressure [Basline (visit 1) and 8 weeks (visit 2)]

5. Aortic Augmentation Pressure [Basline (visit 1) and 8 weeks (visit 2)]

6. Aortic Augmentation Index for Heart Rate [Basline (visit 1) and 8 weeks (visit 2)]

7. Pulse Wave Velocity [Basline (visit 1) and 8 weeks (visit 2)]

8. Heart Rate, Beats Per a Minute [Basline (visit 1) and 8 weeks (visit 2)]

Secondary Outcome Measures

1. Urinary Nitric Oxide Excretion [Basline (visit 1) and 8 weeks (visit 2)]

2. Urinary Isoprostane Excretion [Basline (visit 1) and 8 weeks (visit 2)]

3. Urinary Hydrogen Peroxide Excretion [Baseline (visit 1) and 8 Weeks (visit 2)]

4. Plasma Interleukin Levels [Basline (visit 1) and 8 weeks (visit 2)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego	La Jolla	California	United States	92093

Sponsors and Collaborators

• University of California, San Diego
• Forest Laboratories

Investigators

• Principal Investigator: Daniel O'Connor, MD, University of California, San Diego

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joachim H. Ix, Professor of medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT01202175
• Other Study ID Numbers: 100353
• First Posted: Sep 15, 2010
• Last Update Posted: Aug 21, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Joachim H. Ix, Professor of medicine, University of California, San Diego: Genetic risk of hypertension
• Additional relevant MeSH terms: Hypertension; Prehypertension; Nebivolol

Study Results

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.

Arm/Group Title	All Study Participants
Arm/Group Description	Oral nebivolol 5 mg once daily or Placebo (sugar pill) once dailly. Arms/Groups are combined in this module because the only access to data is a publication that was published before Principal Invesitgator 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.
Period Title: Overall Study
STARTED	50
Nebivolol	25
Pacebo	25
COMPLETED	45
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Nebivolol	Placebo	Total
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily	Total of all reporting groups
Overall Participants	25	25	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.1 (1.8)	30.4 (1.6)	33.7 (1.3)
Sex: Female, Male (Count of Participants)
Female	7 28%	13 52%	20 40%
Male	18 72%	12 48%	30 60%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 12%	5 20%	8 16%
Native Hawaiian or Other Pacific Islander	1 4%	0 0%	1 2%
Black or African American	6 24%	3 12%	9 18%
White	12 48%	13 52%	25 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 12%	4 16%	7 14%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.55 (0.92)	31.03 (1.14)	29.79 (.86)
Starting systolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	127.4 (1.6)	126.2 (1.5)	126.8 (1.1)
Starting diastolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	84.7 (1.5)	84.4 (1.0)	84.5 (0.9)

Outcome Measures

1. Primary Outcome

Title	Aortic Systolic Blood Pressure (SBP)
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	112.7 (2.5)	107.7 (1.9)
Week 8 (visit 2)	106.2 (2.4)	106.6 (2.0)

2. Primary Outcome

Title	Aortic Diastolic Blood Pressure (DBP)
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	79.1 (2.3)	75.9 (1.7)
Week 8 (visit 2)	71.3 (1.9)	74 (1.8)

3. Primary Outcome

Title	Aortic Mean Arterial Pressure (MAP)
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	94.2 (2.1)	90.4 (1.6)
Week 8 (visit 2)	86.8 (1.9)	88.6 (1.9)

4. Primary Outcome

Title	Aortic Pulse Pressure
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	33.6 (2.3)	31.8 (1.4)
Week 8 (visit 2)	34.9 (1.8)	32.6 (1.2)

5. Primary Outcome

Title	Aortic Augmentation Pressure
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	7.4 (2.0)	5.5 (1.0)
Week 8 (visit 2)	6.8 (1.6)	5.3 (1.1)

6. Primary Outcome

Title	Aortic Augmentation Index for Heart Rate
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	14.7 (3.4)	14.5 (2.4)
Week 8 (visit 2)	11.9 (3.8)	12.8 (2.9)

7. Primary Outcome

Title	Pulse Wave Velocity
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	6.73 (0.28)	5.95 (0.19)
Week 8 (visit 2)	6.00 (0.18)	5.78 (0.19)

8. Primary Outcome

Title	Heart Rate, Beats Per a Minute
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	72.0 (1.9)	75.6 (1.9)
Week 8 (visit 2)	64.4 (2.3)	72.1 (2.0)

9. Secondary Outcome

Title	Urinary Nitric Oxide Excretion
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	40.31 (5.05)	61.77 (11.86)
Week 8 (visit 2)	64.38 (14.25)	65.54 (10.54)

10. Secondary Outcome

Title	Urinary Isoprostane Excretion
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	180 (14)	165 (17)
Week 8 (visit 2)	213 (20)	185 (22)

11. Secondary Outcome

Title	Urinary Hydrogen Peroxide Excretion
Time Frame	Baseline (visit 1) and 8 Weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	0.652 (0.274)	0.500 (0.281)
Week 8 (visit 2)	2.79 (1.83)	0.578 (0.194)

12. Secondary Outcome

Title	Plasma Interleukin Levels
Time Frame	Basline (visit 1) and 8 weeks (visit 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol	Placebo
Arm/Group Description	Nebivolol: Oral nebivolol 5 mg once daily
Measure Participants	25	25
Baseline (visit 1)	1.626 (0.598)	1.351 (0.258)
Week 8 (visit 2)	1.647 (0.689)	1.351 (0.258)

Adverse Events

Arm/Group Title	All Study Particpants
Arm/Group Description	Oral nebivolol 5 mg once daily or Placebo (sugar pill) once dailly. Arms/Groups are combined in this module because the only access to data is a publication that was published before Principal Invesitgator 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.
All Cause Mortality
	All Study Particpants
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Serious Adverse Events
	All Study Particpants
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Other (Not Including Serious) Adverse Events
	All Study Particpants
	Affected / at Risk (%)	# Events
Total	1/50 (2%)
Infections and infestations
Flue like symptoms	1/50 (2%)	50

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.