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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01056718
Recruitment Status : Completed
First Posted : January 26, 2010
Results First Posted : March 21, 2016
Last Update Posted : April 18, 2017
Forest Laboratories
Information provided by (Responsible Party):
James Stokes, MD, Mercy Research

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine

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.

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".

Information from the National Library of Medicine

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01056718

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United States, Missouri
St. John's Mercy Cardiovascular Research
St. Louis, Missouri, United States, 63141
Sponsors and Collaborators
Mercy Research
Forest Laboratories
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Principal Investigator: James A. Stokes, M.D. St. John's Mercy Heart & Vascular
Publications of Results:
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Responsible Party: James Stokes, MD, Cardiologist Mercy Hospital, Mercy Research Identifier: NCT01056718    
Other Study ID Numbers: BYS-MD-32
First Posted: January 26, 2010    Key Record Dates
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
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
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