The Effect of Nebivolol on Insulin Sensitivity

• ClinicalTrials.gov Identifier: NCT00125853
• Recruitment Status: Completed
• First Posted: August 2, 2005
• Results First Posted: December 12, 2019
• Last Update Posted: December 12, 2019
• Sponsor: Imperial College London
• Collaborator: Foundation for Circulatory Health
• Information provided by (Responsible Party): Imperial College London

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Hypertension
• Interventions: Drug: Nebivolol; Drug: Atenolol
• Enrollment: 54

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	First is Atenolol Followed by Nebivolol (AN)	First is Nebivolol Followed by Atenolol (NA)
Arm/Group Description	Atenolol 25mg daily for 8 weeks, followed by a 4-week wash-out period, then nebivolol 2.5 mg daily for 8 weeks	Nebivolol 2.5mg daily for 8 weeks, followed by a 4-week wash-out period, then atenolol 25 mg daily for 8 weeks
Period Title: Wash-out (4 Weeks)
Started	27	27
Completed	27	27
Not Completed	0	0
Period Title: First Intervention (8 Weeks)
Started	27	27
Completed	27	27
Not Completed	0	0
Period Title: Wash-out (4 Weeks)
Started	27	27
Completed	24	20
Not Completed	3	7
Reason Not Completed
Lost to Follow-up	3	7
Period Title: Second Intervention (8 Weeks)
Started	24	20
Completed	24	20
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		All Participants
Arm/Group Description		Crossover study design all participants will receive both treatments
Overall Number of Baseline Participants		54
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	54 participants
		61.1 (11)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
	Female	29 53.7%
	Male	25 46.3%
BMI [1]; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	54 participants
		27.2 (6.7)
		[1] Measure Description: kg/m2
Current Smoker; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
		14 25.9%
Ex-smoker; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
		14 25.9%
Systolic Blood Pressure (SBP); Mean (Standard Deviation); Unit of measure: mmHg
	Number Analyzed	54 participants
		129.4 (13.2)
Diastolic Blood Pressure (DBP); Mean (Standard Deviation); Unit of measure: mmHg
	Number Analyzed	54 participants
		81.3 (9.0)
Heart Rate; Mean (Standard Deviation); Unit of measure: Bpm
	Number Analyzed	54 participants
		71.1 (8.9)
HBa1c; Mean (Standard Deviation); Unit of measure: Percentage of glycosylated hemoglobin
	Number Analyzed	54 participants
		5.7 (0.7)
Total Cholesterol; Mean (Standard Deviation); Unit of measure: mmol/L
	Number Analyzed	54 participants
		5.1 (1.0)

Outcome Measures

1. Primary Outcome

Title	Insulin Sensitivity Index (ISI)
Description	Patients were asked to fast for a minimum of 12 hours prior to each oral glucose tolerance test (OGTT). Venous blood was withdrawn for insulin and glucose analysis, 15 minutes and immediately prior to, and 30, 60, 90 and 120 minutes following an oral glucose load. For each OGTT, the Insulin Sensitivity Index (ISI) was calculated using the standard method for oral glucose tolerance testing. For each OGTT, the Insulin Sensitivity Index (ISI) was calculated using the standard method for oral glucose tolerance testing.
Time Frame	Baseline, 15, 30, 60, 90, 120m following oral glucose load, at baseline and at the end of each phase(8 weeks treatment

Outcome Measure Data

Analysis Population Description

Patients with mild-to-moderate essential hypertension, aged 18 years or above, with blood pressure controlled to <140/85 mmHg on a maximum of two antihypertensive drugs, were recruited from the Peart-Rose Hypertension clinic at St Mary's Hospital in West London and from local general practices.

Arm/Group Title	Atenolol	Nebivolol
Arm/Group Description:	Participants received Atenolol 25mg daily for 8 weeks	Participants received Nebivolol 2.5mg daily for 8 weeks
Overall Number of Participants Analyzed	44	44
Mean (Inter-Quartile Range); Unit of Measure: factor
Before	82.36; (50.8 to 116.9)	80.70; (52.6 to 114.7)
After	75.47; (50.6 to 144.9)	81.54; (50.9 to 114.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Nebivolol
	Comments	Comparing treatment effects on ISI
	Type of Statistical Test	Other
	Comments	Linear Mixed effect Modelling, adjusted for baseline values and period effect Difference of LSMeans treatment effect (SE) = 0.05 (0.09)
Statistical Test of Hypothesis	P-Value	0.60
	Comments	[Not Specified]
	Method	Linear Mixed effect Modelling, adjusted
	Comments	[Not Specified]

2. Secondary Outcome

Title	24 Hour Systolic Blood Pressure
Description	The 24-h Ambulatory Blood Pressure Monitoring (ABPM) was recorded at the beginning and end of each beta-blocker treatment period. BP was automatically recorded for 24 h at 30 min intervals. The time periods from 0700h to 2200h and from 2200h to 0700h were defined as daytime and night-time, respectively.
Time Frame	Before and after 8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atenolol	Nebivolol
Arm/Group Description:	Participants received Atenolol 25mg daily for 8 weeks	Participants received Nebivolol 2.5mg daily for 8 weeks
Overall Number of Participants Analyzed	44	44
Mean (Standard Deviation); Unit of Measure: mmHg
SBP before	128.4 (9.7)	130.4 (9.5)
SBP after	117.2 (9.2)	121.2 (8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Nebivolol
	Comments	Comparing treatment effects on ABPM
	Type of Statistical Test	Other
	Comments	Linear Mixed effect Model, adjusted for baseline values and period effect Difference of LSMeans treatment effect (SE) = -2.59 (1.34)
Statistical Test of Hypothesis	P-Value	0.06
	Comments	[Not Specified]
	Method	Linear Mixed effect Model, adjusted for
	Comments	[Not Specified]

3. Secondary Outcome

Title	Total Cholesterol
Description	Fasting blood samples were taken at the beginning and end of each treatment period.
Time Frame	Before and after 8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atenolol	Nebivolol
Arm/Group Description:	Participants received Atenolol 25mg daily for 8 weeks	Participants received Nebivolol 2.5mg daily for 8 weeks
Overall Number of Participants Analyzed	44	44
Mean (Standard Deviation); Unit of Measure: mmol/L
Before	5.0 (1.0)	5.1 (0.9)
After	4.9 (1.0)	5.1 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Nebivolol
	Comments	Comparing treatment effects on total cholesterol
	Type of Statistical Test	Other
	Comments	Linear Mixed effect Model, adjusted for baseline values and period effect Difference of LSMeans treatment effect (SE) = -0/09 (0.14)
Statistical Test of Hypothesis	P-Value	0.51
	Comments	[Not Specified]
	Method	Linear Mixed effect Modelling, adjusted
	Comments	[Not Specified]

4. Secondary Outcome

Title	HbA1c
Description	Fasting blood samples were taken at the beginning and end of each treatment period.
Time Frame	Before and after 8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atenolol	Nebivolol
Arm/Group Description:	Participants received Atenolol 25mg daily for 8 weeks	Participants received Nebivolol 2.5mg daily for 8 weeks
Overall Number of Participants Analyzed	44	44
Mean (Standard Deviation); Unit of Measure: percentage of glycosylated hemoglobin
Before	5.7 (0.8)	5.7 (0.8)
After	5.7 (0.4)	5.7 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Nebivolol
	Comments	Comparing treatment effects on HbA1c
	Type of Statistical Test	Other
	Comments	Linear Mixed effect Model, adjusted for baseline values and period effect Difference of LSMeans treatment effect (SE) =0.02 (0.03)
Statistical Test of Hypothesis	P-Value	0.48
	Comments	[Not Specified]
	Method	Linear Mixed effect Modelling, adjusted
	Comments	[Not Specified]

5. Secondary Outcome

Title	BMI
Description	Body weights and heights were taken at the beginning and end of each treatment period.
Time Frame	Before and after 8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atenolol	Nebivolol
Arm/Group Description:	Participants received Atenolol 25mg daily for 8 weeks	Participants received Nebivolol 2.5mg daily for 8 weeks
Overall Number of Participants Analyzed	44	44
Mean (Standard Deviation); Unit of Measure: kg/m^2
Before	28.1 (4.6)	28.2 (4.7)
After	28.0 (4.4)	28.3 (4.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atenolol, Nebivolol
	Comments	Comparing treatment effects on BMI
	Type of Statistical Test	Other
	Comments	Linear Mixed effect Model, adjusted for baseline values and period effect Difference of LSMeans treatment effect (SE) = -0.21(0.13)
Statistical Test of Hypothesis	P-Value	0.09
	Comments	[Not Specified]
	Method	Linear Mixed effect Modelling, adjusted
	Comments	[Not Specified]

Adverse Events

Time Frame	32 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Atenolol 25mg Daily	Nebivolol 2.5mg Daily
Arm/Group Description	atenolol 25mg daily Atenolol: Atenolol 25mg daily	nebivolol 2.5mg daily Nebivolol: Nebivolol 25mg daily
All-Cause Mortality
	Atenolol 25mg Daily	Nebivolol 2.5mg Daily
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/54 (0.00%)	0/54 (0.00%)
Serious Adverse Events
	Atenolol 25mg Daily	Nebivolol 2.5mg Daily
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/54 (0.00%)	0/54 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Atenolol 25mg Daily	Nebivolol 2.5mg Daily
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/54 (0.00%)	0/54 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: Professor Neil Poulter
• Organization: Imperial College London
• Phone: +44 2075943445
• EMail: n.poulter@imperial.ac.uk

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT00125853
• Other Study ID Numbers: NPSW02
• First Submitted: July 29, 2005
• First Posted: August 2, 2005
• Results First Submitted: June 12, 2019
• Results First Posted: December 12, 2019
• Last Update Posted: December 12, 2019