Effects of Nebivolol on Exercise Tolerance and Left Ventricular Systolic and Diastolic Function

The goal of this pilot study is to effectively treat hypertension in subjects with either known or newly diagnosed hypertension and concurrent evidence of diastolic dysfunction. Due to the unique properties of nebivolol, it is hypothesized that there will be improvements in left ventricular (LV) systolic and diastolic function manifesting as increase exercise capacity in this patient population with primarily LV diastolic dysfunction. The present study was performed to determine the effects of nebivolol on blood pressure, exercise tolerance and parameters of left ventricular systolic and diastolic function in a group of hypertensive patients with echocardiographic evidence diastolic dysfunction.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Nebivolol

Detailed Description

Prior to the initiation of Nebivolol and after 10 weeks of Nebivolol therapy, subjects underwent a resting 2D echocardiogram including routine sampling of mitral valve (MV) inflow and LV tissue Doppler imaging as well as a symptom limited exercise treadmill stress test with echocardiographic imaging. Primary endpoints were 1) changes in systolic blood pressure before and after 10 weeks of treatment and 2) changes in exercise capacity as determined by exercise duration and metabolic equivalent (MET) level before and after treatment. Secondary endpoints were changes in exercise hemodynamics and Doppler echocardiographic parameters of LV systolic and diastolic function and quality of life before and after 10 weeks of nebivolol treatment. Subjects completed an EuroQol (EQ-SD) Quality of Life questionnaire which is a standardized measure of health status developed by the EuroQol group as a simple general measure of health at baseline and at conclusion of the 10 week trial period.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • St. John's Mercy Cardiovascular Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis (new or established) hypertension, defined by serial measurements >/= 140/90
• Evidence of diastolic dysfunction on echocardiography measured by tissue Doppler

Exclusion Criteria:

• Severe bronchospastic disease/ reactive airway disease
• Inability to tolerate beta blocker therapy including: >1st degree atrioventricular (AV) block, symptomatic hypotension, symptomatic bradycardia,
• Subjects with physical limitations that would prevent them from participating in an exercise treadmill test
• Age <18 or >90 years
• Those with life expectancy <1 year
• Subjects with class III/IV New York Heart Association (NYHA) heart failure symptoms
• Chronic Kidney Disease 3 or greater (CrCl <30 cc/min)
• Subjects with active ischemia or evidence of ischemia on initial stress echocardiography

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Nebivolol treatment; 10 week open label nebivolol treatment.

Drug: Nebivolol; Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure. The dose was titrated by doubling the previous dosage to achieve BP less than or equal to 130/80 mm Hg at 2 weeks and 4 weeks. The mean dose of nebivolol used week 4 through week 10 was 7.8 mg. It should be noted that nebivolol was added to the subject's existing stable antihypertensive regimen which included a mean of 2 other medications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting Systolic BP		10 Weeks
Exercise Duration		10 Weeks
Metabolic Equivalent (METS) Level	METs is a measure of exercise capacity. One MET is defined as 3.5 mL 02 uptake/kg per minute which is the resting oxygen uptake in a sitting position. The Bruce protocol consisted of successive 3 minute stages each of which requires the subject to walk at a faster speed and higher grade of incline. Each stage is assigned a MET level. The achieved exercise capacity in METs has been shown to be predictive in older adult population of survival with higher MET levels associated with improved survival.	10 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diastolic BP		10 Week
Peak Stress Systolic BP		10 Week
Peak Stress Diastolic BP		10 Week
Resting Heart Rate		10 Week
Stress Heart Rate		10 Week
Resting EF		10 Weeks
Stress EF		10 Week
Resting Stroke Volume		10 weeks
Stress Stroke Volume		10 week
Resting Cardiac Output		10 week
Stress Cardiac Output		10 week
LV End Diastolic Diameter		10 week
LV End Systolic Diameter		10 week
LV Mass		10 week
Mitral Valve Inflow (E) Velocity		10 Week
Mitral Valve Inflow (A) Velocity		10 Week
Mitral Valve E/A Ratio	mitral valve doppler E velocity to A velocity	10 Week
Mitral Valve Deceleration Time		10 Week
Mitral Valve Tissue Doppler Velocity (e')		10 Week
Mitral Valve Tissue Doppler Velocity (a')		10 Week
E/e' Ratio		10 Week
Pulmonary Vein Peak Systolic Velocity		10 Week
Pulmonary Vein Peak Diastolic Velocity		10 Week
Quality of Life	Quality of life was assessed by a visual analogue scale before and after 10 weeks of nebivolol. The subjects self reported assessment of his/her overall health was recorded on a vertical visual analogue scale where 100 is the "best imaginable health state" and 0 is the "worst imaginable health state".	10 Weeks

Collaborators and Investigators

• Sponsor: Mercy Research
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: James A. Stokes, M.D., St. John's Mercy Heart & Vascular

Publications and helpful links

General Publications

• EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990 Dec;16(3):199-208. doi: 10.1016/0168-8510(90)90421-9.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: January 25, 2010
• First Submitted That Met QC Criteria: January 25, 2010
• First Posted (Estimate): January 26, 2010

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Nebivolol; Diastolic Function
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; 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: BYS-MD-32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO