The Effect of Nebivolol on Insulin Sensitivity

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00125853
• Collaborator: Foundation for Circulatory Health (Other)
• Enrollment: 54
• Location: 1
• Arms: 2
• Actual Duration (Months): 30.1
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of this study is to conduct a randomised trial to compare the insulin sensitivity, 24 hour blood pressure profile, and tolerability of nebivolol plus a thiazide-like diuretic versus atenolol plus a thiazide-like diuretic.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Nebivolol; Drug: Atenolol	N/A

Detailed Description

Retrospective studies of treated hypertensive cohorts have strongly implicated beta blocker therapy as increasing the risk of developing new-onset diabetes. This has led to the latest British Hypertension Society guidelines advising caution when using beta blockers particularly in combination with thiazide-like diuretics. However the National Institute of Clinical Excellence recommends beta-blocker + thiazide combinations as the treatment of choice in patients who are not at increased risk of developing diabetes. Nebivolol is a newer class of beta blocker. Some studies in diabetic hypertensive patients have suggested that nebivolol does not impair insulin sensitivity. The aim of this study is to compare the effect on insulin sensitivity of nebivolol versus atenolol, both in combination with a thiazide-like diuretic, in a group of non-diabetic hypertensive patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Trial to Compare the Effects of Nebivolol Versus Atenolol on Various Cardiovascular Measurements Including Insulin Sensitivity
• Actual Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: atenolol 25mg daily atenolol 25mg daily	Drug: Atenolol; Atenolol 25mg daily
Active Comparator: nebivolol 2.5mg daily nebivolol 2.5mg daily	Drug: Nebivolol; Nebivolol 2.5mg daily

Outcome Measures

Primary Outcome Measures

1. Insulin Sensitivity Index (ISI) [Baseline, 15, 30, 60, 90, 120m following oral glucose load, at baseline and at the end of each phase(8 weeks treatment]

   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.

Secondary Outcome Measures

1. 24 Hour Systolic Blood Pressure [Before and after 8 weeks of treatment]

   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.

2. Total Cholesterol [Before and after 8 weeks of treatment]

   Fasting blood samples were taken at the beginning and end of each treatment period.

3. HbA1c [Before and after 8 weeks of treatment]

   Fasting blood samples were taken at the beginning and end of each treatment period.

4. BMI [Before and after 8 weeks of treatment]

   Body weights and heights were taken at the beginning and end of each treatment period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females aged 18 or above

• Blood pressure that meets any of the three following criteria:

• BP should be <140/85 mmHg on a maximum of two anti-hypertensive drugs

Exclusion Criteria:

• contraindications to beta-blockade

• contraindications to thiazide use

• if there was a history of asthma, diabetes, heart failure, bradycardia, atrial fibrillation, AV conduction disturbances

• concurrent treatment with verapamil & dilitiazem

• childbearing women

• compelling indication for treatment with a beta blocker

• any condition that will interfere with the treatment or the patient's ability to complete the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial College London	Paddington	London	United Kingdom	W2 1PG

Sponsors and Collaborators

• Imperial College London
• Foundation for Circulatory Health

Investigators

• Principal Investigator: Neil R Poulter, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT00125853
• Other Study ID Numbers: NPSW02
• First Posted: Aug 2, 2005
• Last Update Posted: Dec 12, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: blood pressure; insulin sensitivity; beta blockers; randomised double blind crossover trial
• Additional relevant MeSH terms: Insulin Resistance; Hypersensitivity; Atenolol; Nebivolol

Study Results

Participant Flow

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: Wash-out (4 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
Period Title: Wash-out (4 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 Participants	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.1 (11)
Sex: Female, Male (Count of Participants)
Female	29 53.7%
Male	25 46.3%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.2 (6.7)
Current Smoker (Count of Participants)
Count of Participants [Participants]	14 25.9%
Ex-smoker (Count of Participants)
Count of Participants [Participants]	14 25.9%
Systolic Blood Pressure (SBP) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	129.4 (13.2)
Diastolic Blood Pressure (DBP) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	81.3 (9.0)
Heart Rate (bpm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [bpm]	71.1 (8.9)
HBa1c (percentage of glycosylated hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated hemoglobin]	5.7 (0.7)
Total Cholesterol (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	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
Measure Participants	44	44
Before	82.36	80.70
After	75.47	81.54

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
	Method	Linear Mixed effect Modelling, adjusted
	Comments

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
Measure Participants	44	44
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
	Method	Linear Mixed effect Model, adjusted for
	Comments

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
Measure Participants	44	44
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
	Method	Linear Mixed effect Modelling, adjusted
	Comments

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
Measure Participants	44	44
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
	Method	Linear Mixed effect Modelling, adjusted
	Comments

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
Measure Participants	44	44
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
	Method	Linear Mixed effect Modelling, adjusted
	Comments

Adverse Events

Time Frame	32 weeks
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/54 (0%)
Serious Adverse Events
	Atenolol 25mg Daily		Nebivolol 2.5mg Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Atenolol 25mg Daily		Nebivolol 2.5mg Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/54 (0%)

Limitations/Caveats

[Not Specified]

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.