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

• Sponsor: Mercy Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT01056718
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 53
• Location: 1
• Arm: 1
• Duration (Months): 53.9
• Patients Per Site Per Month: 1

Study Details

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	N/A

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
• 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: Nov 1, 2009
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Resting Systolic BP [10 Weeks]

2. Exercise Duration [10 Weeks]

3. Metabolic Equivalent (METS) Level [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 [10 Week]

2. Peak Stress Systolic BP [10 Week]

3. Peak Stress Diastolic BP [10 Week]

4. Resting Heart Rate [10 Week]

5. Stress Heart Rate [10 Week]

6. Resting EF [10 Weeks]

7. Stress EF [10 Week]

8. Resting Stroke Volume [10 weeks]

9. Stress Stroke Volume [10 week]

10. Resting Cardiac Output [10 week]

11. Stress Cardiac Output [10 week]

12. LV End Diastolic Diameter [10 week]

13. LV End Systolic Diameter [10 week]

14. LV Mass [10 week]

15. Mitral Valve Inflow (E) Velocity [10 Week]

16. Mitral Valve Inflow (A) Velocity [10 Week]

17. Mitral Valve E/A Ratio [10 Week]

    mitral valve doppler E velocity to A velocity

18. Mitral Valve Deceleration Time [10 Week]

19. Mitral Valve Tissue Doppler Velocity (e') [10 Week]

20. Mitral Valve Tissue Doppler Velocity (a') [10 Week]

21. E/e' Ratio [10 Week]

22. Pulmonary Vein Peak Systolic Velocity [10 Week]

23. Pulmonary Vein Peak Diastolic Velocity [10 Week]

24. Quality of Life [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

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James Stokes, MD, Cardiologist Mercy Hospital, Mercy Research
• ClinicalTrials.gov Identifier: NCT01056718
• Other Study ID Numbers: BYS-MD-32
• First Posted: Jan 26, 2010
• Last Update Posted: Apr 18, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by James Stokes, MD, Cardiologist Mercy Hospital, Mercy Research: Diastolic Function; Nebivolol
• Additional relevant MeSH terms: Hypertension; Nebivolol

Study Results

Participant Flow

Recruitment Details	Recruited from the outpatient office at Mercy St. Louis between January 2010 and August 2012. The inclusion criteria were new or established hypertension as defined by serial BP measurements greater than or equal to 140/90 and evidence of left ventricular (LV) diastolic dysfunction as defined by a routine Doppler within a year of enrollment.

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	10 week open label nebivolol treatment.
Period Title: Overall Study
STARTED	53
COMPLETED	50
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	All subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Overall Participants	53
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 37.7%
>=65 years	33 62.3%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66 (10)
Sex: Female, Male (Count of Participants)
Female	20 37.7%
Male	33 62.3%
Region of Enrollment (participants) [Number]
United States	53 100%
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	31 (5)
Resting Systolic BP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	145 (19)
Exercise Duration (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	385 (174)
Metabolic Equivalent (Mets) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Mets]	6.2 (3.1)
Resting Diastolic BP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	79 (11)
Peak Stress Systolic BP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	178 (23)
Peak Stress Diastolic BP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	75 (15)
Resting Heart Rate (Beats per Minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Beats per Minute]	69 (11)
Stress Heart Rate (Beats per Minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Beats per Minute]	136 (24)
Resting Ejection Fraction (EF) (Percent of LV end diastolic volume) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent of LV end diastolic volume]	61 (10)
Stress EF (Percent of LV end diastolic volume) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent of LV end diastolic volume]	67 (10)
Resting Stroke Volume (ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml]	46 (15)
Stress Stroke Volume (ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml]	47 (13)
Resting Cardiac Output (L per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [L per minute]	3.1 (1.1)
Stress Cardiac Output (L per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [L per minute]	5.6 (2.2)
LV End Diastolic Diameter (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	4.7 (0.5)
LV End Systolic Diameter (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	3.0 (0.8)
LV Mass (grams) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams]	163 (52)
Mitral Valve Inflow (E) Velocity (cm/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm/s]	77 (24)
Mitral Valve Inflow (A) Velocity (cm/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm/s]	91 (21)
Mitral Valve E/A Ratio (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	.86 (.18)
Mitral Valve Deceleration Time (ms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ms]	229 (62)
Mitral Valve Tissue Doppler Velocity (e') (cm/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm/s]	7.6 (1.9)
Mitral Valve Tissue Doppler Velocity (a') (cm/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm/s]	11.8 (2.9)
E/e' Ratio (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	10.8 (4.7)
Pulmonary Vein Peak Systolic Velocity (cm/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm/s]	62 (13)
Pulmonary Vein Peak Diastolic Velocity (cm/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm/s]	47 (13)
Quality of Life (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	77 (12)

Outcome Measures

1. Primary Outcome

Title	Resting Systolic BP
Time Frame	10 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [mm Hg]	135 (17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of treatment. Each subject served as his/her own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Exercise Duration
Time Frame	10 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [Seconds]	419 (180)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

3. Primary Outcome

Title	Metabolic Equivalent (METS) Level
Description	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.
Time Frame	10 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [METS]	6.7 (3.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Diastolic BP
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [mm Hg]	76 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.078
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Peak Stress Systolic BP
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [mm Hg]	171 (26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.186
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Peak Stress Diastolic BP
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [mm Hg]	68 (17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Resting Heart Rate
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	All subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [Beats per Minute]	65 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Stress Heart Rate
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	All subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [Beats per Minute]	118 (24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.06
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Resting EF
Time Frame	10 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	All subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [Percent of LV end diastolic volume]	63 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	Stress EF
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [Percent of LV end diastolic volume]	72 (10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

11. Secondary Outcome

Title	Resting Stroke Volume
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [ml]	48 (14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.85
	Comments
	Method	t-test, 2 sided
	Comments

12. Secondary Outcome

Title	Stress Stroke Volume
Time Frame	10 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [ml]	51 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.40
	Comments
	Method	t-test, 2 sided
	Comments

13. Secondary Outcome

Title	Resting Cardiac Output
Time Frame	10 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [L per minute]	3.0 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.64
	Comments
	Method	t-test, 2 sided
	Comments

14. Secondary Outcome

Title	Stress Cardiac Output
Time Frame	10 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [L per minute]	5.3 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.49
	Comments
	Method	t-test, 2 sided
	Comments

15. Secondary Outcome

Title	LV End Diastolic Diameter
Time Frame	10 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm]	4.8 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.47
	Comments
	Method	t-test, 2 sided
	Comments

16. Secondary Outcome

Title	LV End Systolic Diameter
Time Frame	10 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm]	3.1 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.55
	Comments
	Method	t-test, 2 sided
	Comments

17. Secondary Outcome

Title	LV Mass
Time Frame	10 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [grams]	167 (47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.64
	Comments
	Method	t-test, 2 sided
	Comments

18. Secondary Outcome

Title	Mitral Valve Inflow (E) Velocity
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm/s]	85 (21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

19. Secondary Outcome

Title	Mitral Valve Inflow (A) Velocity
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm/s]	90 (23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.526
	Comments
	Method	t-test, 2 sided
	Comments

20. Secondary Outcome

Title	Mitral Valve E/A Ratio
Description	mitral valve doppler E velocity to A velocity
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [Ratio]	0.97 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

21. Secondary Outcome

Title	Mitral Valve Deceleration Time
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [ms]	227 (55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.925
	Comments
	Method	t-test, 2 sided
	Comments

22. Secondary Outcome

Title	Mitral Valve Tissue Doppler Velocity (e')
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm/s]	8.7 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

23. Secondary Outcome

Title	Mitral Valve Tissue Doppler Velocity (a')
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm/s]	11.5 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.458
	Comments
	Method	t-test, 2 sided
	Comments

24. Secondary Outcome

Title	E/e' Ratio
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [Ratio]	10.5 (4.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.561
	Comments
	Method	t-test, 2 sided
	Comments

25. Secondary Outcome

Title	Pulmonary Vein Peak Systolic Velocity
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm/s]	63 (10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.734
	Comments
	Method	t-test, 2 sided
	Comments

26. Secondary Outcome

Title	Pulmonary Vein Peak Diastolic Velocity
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [cm/s]	51 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nebivolol Treatment
	Comments	Nebivolol treatment group refers to 50 patients that completed 10 weeks of open label nebivolol treatment. Results were compared using paired T-tests in a pre - post study design before and after 10 weeks of his/her treatment. Each subject served as own control.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.129
	Comments
	Method	t-test, 2 sided
	Comments

27. Secondary Outcome

Title	Quality of Life
Description	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".
Time Frame	10 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol Treatment
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
Measure Participants	50
Mean (Standard Deviation) [units on a scale]	78 (15)

Adverse Events

Time Frame	Patients were monitored for 10 weeks for any adverse side effects resulting in discontinuation or decrease in nebivolol dosage after the titration period. They were also monitored for cardiovascular events during the treatment period.
Arm/Group Title	Starting on 5 mg of Nebivolol Then Titrated
Arm/Group Description	all subjects will begin an initial dosage of 5mg of Nebivolol titrated (doubling of previous dose) to optimal blood pressure below 130/80 at 2 and 4 weeks after treatment initiation. Nebivolol: Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure.
All Cause Mortality
	Starting on 5 mg of Nebivolol Then Titrated
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Starting on 5 mg of Nebivolol Then Titrated
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Other (Not Including Serious) Adverse Events
	Starting on 5 mg of Nebivolol Then Titrated
	Affected / at Risk (%)	# Events
Total	0/50 (0%)

Limitations/Caveats

There was no placebo control. All patients received nebivolol and served as their own control before and after treatment. This study had a small study population and short duration.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.