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

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.

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Pre-hypertension
• Intervention / Treatment: Drug: Nebivolol

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: Daniel O'Connor, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: June 24, 2010
• First Submitted That Met QC Criteria: September 14, 2010
• First Posted (ESTIMATE): September 15, 2010

Study Record Updates

• Last Update Posted (ACTUAL): August 21, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Genetic risk of hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Prehypertension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-1 Receptor Agonists; Nebivolol
• Other Study ID Numbers: 100353