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

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
James Stokes, MD, St. John's Health System, Missouri
ClinicalTrials.gov Identifier:
NCT01056718
First received: January 25, 2010
Last updated: February 19, 2016
Last verified: February 2016
  Purpose
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 Intervention
Hypertension
Drug: Nebivolol

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Nebivolol on Exercise Tolerance and Left Ventricular Systolic and Diastolic Function

Resource links provided by NLM:


Further study details as provided by St. John's Health System, Missouri:

Primary Outcome Measures:
  • Resting Systolic BP [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
  • Exercise Duration [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
  • Metabolic Equivalent (METS) Level [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    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:
  • Diastolic BP [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Peak Stress Systolic BP [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Peak Stress Diastolic BP [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Resting Heart Rate [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Stress Heart Rate [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Resting EF [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
  • Stress EF [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Resting Stroke Volume [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  • Stress Stroke Volume [ Time Frame: 10 week ] [ Designated as safety issue: No ]
  • Resting Cardiac Output [ Time Frame: 10 week ] [ Designated as safety issue: No ]
  • Stress Cardiac Output [ Time Frame: 10 week ] [ Designated as safety issue: No ]
  • LV End Diastolic Diameter [ Time Frame: 10 week ] [ Designated as safety issue: No ]
  • LV End Systolic Diameter [ Time Frame: 10 week ] [ Designated as safety issue: No ]
  • LV Mass [ Time Frame: 10 week ] [ Designated as safety issue: No ]
  • Mitral Valve Inflow (E) Velocity [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Mitral Valve Inflow (A) Velocity [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Mitral Valve E/A Ratio [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
    mitral valve doppler E velocity to A velocity

  • Mitral Valve Deceleration Time [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Mitral Valve Tissue Doppler Velocity (e') [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Mitral Valve Tissue Doppler Velocity (a') [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • E/e' Ratio [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Pulmonary Vein Peak Systolic Velocity [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Pulmonary Vein Peak Diastolic Velocity [ Time Frame: 10 Week ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    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".


Enrollment: 53
Study Start Date: November 2009
Study Completion Date: May 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01056718

Locations
United States, Missouri
St. John's Mercy Cardiovascular Research
St. Louis, Missouri, United States, 63141
Sponsors and Collaborators
St. John's Health System, Missouri
Forest Laboratories
Investigators
Principal Investigator: James A. Stokes, M.D. St. John's Mercy Heart & Vascular
  More Information

Publications:
Responsible Party: James Stokes, MD, Cardiologist Mercy Hospital, St. John's Health System, Missouri
ClinicalTrials.gov Identifier: NCT01056718     History of Changes
Other Study ID Numbers: BYS-MD-32 
Study First Received: January 25, 2010
Results First Received: December 16, 2015
Last Updated: February 19, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by St. John's Health System, Missouri:
Diastolic Function
Nebivolol

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on December 09, 2016