The Effect of Nebivolol on Insulin Sensitivity

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Trial to Compare the Effects of Nebivolol Versus Atenolol on Various Cardiovascular Measurements Including Insulin Sensitivity

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Nebivolol
* Drug: Atenolol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: atenolol 25mg daily<br>atenolol 25mg daily | Drug: Atenolol<br>* Atenolol 25mg daily<br>|
| Active Comparator: nebivolol 2.5mg daily<br>nebivolol 2.5mg daily | Drug: Nebivolol<br>* Nebivolol 2.5mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity Index (ISI) | 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. | Baseline, 15, 30, 60, 90, 120m following oral glucose load, at baseline and at the end of each phase(8 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 Hour Systolic Blood Pressure | 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. | Before and after 8 weeks of treatment | 
| Total Cholesterol | Fasting blood samples were taken at the beginning and end of each treatment period. | Before and after 8 weeks of treatment | 
| HbA1c | Fasting blood samples were taken at the beginning and end of each treatment period. | Before and after 8 weeks of treatment | 
| BMI | Body weights and heights were taken at the beginning and end of each treatment period. | Before and after 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood pressure, insulin sensitivity, beta blockers, randomised double blind crossover trial