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

• ClinicalTrials.gov Identifier: NCT01056718
• Recruitment Status: Completed
• First Posted: January 26, 2010
• Results First Posted: March 21, 2016
• Last Update Posted: April 18, 2017
• Sponsor: Mercy Research
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): James Stokes, MD, Mercy Research

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Nebivolol	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Nebivolol on Exercise Tolerance and Left Ventricular Systolic and Diastolic Function
• Study Start Date: November 2009
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm

Intervention/treatment

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.

Outcome Measures

Primary Outcome Measures :

1. Resting Systolic BP [ Time Frame: 10 Weeks ]
2. Exercise Duration [ Time Frame: 10 Weeks ]
3. Metabolic Equivalent (METS) Level [ Time Frame: 10 Weeks ]
   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.

Secondary Outcome Measures :

1. Diastolic BP [ Time Frame: 10 Week ]
2. Peak Stress Systolic BP [ Time Frame: 10 Week ]
3. Peak Stress Diastolic BP [ Time Frame: 10 Week ]
4. Resting Heart Rate [ Time Frame: 10 Week ]
5. Stress Heart Rate [ Time Frame: 10 Week ]
6. Resting EF [ Time Frame: 10 Weeks ]
7. Stress EF [ Time Frame: 10 Week ]
8. Resting Stroke Volume [ Time Frame: 10 weeks ]
9. Stress Stroke Volume [ Time Frame: 10 week ]
10. Resting Cardiac Output [ Time Frame: 10 week ]
11. Stress Cardiac Output [ Time Frame: 10 week ]
12. LV End Diastolic Diameter [ Time Frame: 10 week ]
13. LV End Systolic Diameter [ Time Frame: 10 week ]
14. LV Mass [ Time Frame: 10 week ]
15. Mitral Valve Inflow (E) Velocity [ Time Frame: 10 Week ]
16. Mitral Valve Inflow (A) Velocity [ Time Frame: 10 Week ]
17. Mitral Valve E/A Ratio [ Time Frame: 10 Week ]
    mitral valve doppler E velocity to A velocity
18. Mitral Valve Deceleration Time [ Time Frame: 10 Week ]
19. Mitral Valve Tissue Doppler Velocity (e') [ Time Frame: 10 Week ]
20. Mitral Valve Tissue Doppler Velocity (a') [ Time Frame: 10 Week ]
21. E/e' Ratio [ Time Frame: 10 Week ]
22. Pulmonary Vein Peak Systolic Velocity [ Time Frame: 10 Week ]
23. Pulmonary Vein Peak Diastolic Velocity [ Time Frame: 10 Week ]
24. Quality of Life [ Time Frame: 10 Weeks ]
    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".

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Missouri

St. John's Mercy Cardiovascular Research

St. Louis, Missouri, United States, 63141

Sponsors and Collaborators

Mercy Research

Forest Laboratories

Investigators

• Principal Investigator: James A. Stokes, M.D.; St. John's Mercy Heart & Vascular

More Information

Publications of Results:

EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990 Dec;16(3):199-208.

• Responsible Party: James Stokes, MD, Cardiologist Mercy Hospital, Mercy Research
• ClinicalTrials.gov Identifier: NCT01056718 History of Changes
• Other Study ID Numbers: BYS-MD-32
• First Posted: January 26, 2010
• Results First Posted: March 21, 2016
• Last Update Posted: April 18, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by James Stokes, MD, Mercy Research:

Diastolic Function; Nebivolol

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Nebivolol; Antihypertensive Agents; Vasodilator Agents; Adrenergic beta-1 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs