Study of the Glycemic Effects of Nebivolol Compared With Metoprolol and HCTZ in Diabetic Hypertensive Patients

Study Overview
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Brief Summary
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This study will evaluate the effects of nebivolol on glycemic control compared with metoprolol and HCTZ in patients with hypertension and type 2 diabetes mellitus

Official Title
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Glycemic Effects of Nebivolol Compared With Metoprolol Extended Release and Compared With Hydrochlorothiazide In Hypertensive Patients With Type 2 Diabetes Mellitus: A Pilot Study

Conditions
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Hypertension, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Nebivolol
* Drug: Metoprolol ER
* Drug: HCTZ


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Male or female, 18-85 years of age Blood pressure in the range of 130 to 179/80 to 109 mmHg Currently using either an ACE inhibitor or an ARB alone or (an ACE inhibitor or an ARB and up to two other drugs for treatment of high blood pressure). (Patients may be on both an ACE inhibitor and ARB, but would need to be taken off one.) Stable medication regimen for high blood pressure for at least one month prior to screening Stable type 2 diabetes mellitus for at least 3 months prior to screening that is controlled by any or all of the following: diet and antidiabetic medications that may include fixed-dose insulin HgbA1c 6.5 to 8.5% (This is measured at the screening visit) EXCLUSION CRITERIA: Use of any beta blocker within one month prior to screening Use of clonidine within 3 months prior to screening Diagnosis of hyperthyroidism as evidenced by abnormal lab markers Any disorder requiring the intermittent or chronic use of systemic corticosteroids Diagnosis of hyperthyroidism as determined by lab markers done at screening Active liver disease as determined by lab markers Kidney impairment; estimated GFR < 60 mL/min/1.73 m2 History of heart attack, clinically significant arrhythmia, unstable angina, coronary angioplasty/bypass surgery, stroke, or TIA in 3 months prior to screening Chronic heart failure Drug or alcohol abuse within 2 years prior to screening History of sensitivity to any beta blocker, HCTZ, sulfa drug, or calcium channel blocker Participation in another research study within 30 days prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Nebivolol 5 mg (overencapsulated 5-mg marketed tablet), oral administration Nebivolol 10 mg (overencapsulated 10-mg marketed tablet), oral administration Nebivolol 20 mg (overencapsulated 20-mg marketed tablet) oral administration Nebivolol 40 mg (two overencapsulated 20-mg tablets) oral administration Open-label amlodipine may be given | Drug: Nebivolol<br>* Nebivolol 5 mg (overencapsulated 5-mg marketed tablet), oral administration Nebivolol 10 mg (overencapsulated 10-mg marketed tablet), oral administration Nebivolol 20 mg (overencapsulated 20-mg marketed tablet) oral administration Nebivolol 40 mg (two overencapsulated 20-mg tablets) oral administration<br>* Other names: Bystolic (TM);|
| Active Comparator: 2<br>Metoprolol ER 50 mg (overencapsulated 50-mg tablet) oral administration Metoprolol ER 100 mg (two overencapsulated 50-mg tablets) oral administration Metoprolol ER 200 mg (overencapsulated 200-mg tablet) oral administration Metoprolol ER 400 mg (two overencapsulated 200-mg tablets) oral administration Open-label amlodipine may be given | Drug: Metoprolol ER<br>* Metoprolol ER 50 mg (overencapsulated 50-mg tablet) oral administration Metoprolol ER 100 mg (two overencapsulated 50-mg tablets) oral administration Metoprolol ER 200 mg (overencapsulated 200-mg tablet) oral administration Metoprolol ER 400 mg (two overencapsulated 200-mg tablets) oral administration<br>|
| Active Comparator: 3<br>HCTZ 12.5 mg (overencapsulated 12.5 capsule), oral administration HCTZ 25 mg (two capsules, overencapsulated 12.5-mg capsules), oral administration Open-label amlodipine may be given | Drug: HCTZ<br>* HCTZ 12.5 mg (overencapsulated 12.5 capsule), oral administration HCTZ 25 mg (two capsules, overencapsulated 12.5-mg capsules), oral administration<br>* Other names: Hydrochlorothorazide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Glycosylated Hemoglobin (HbA1c) at Week 26 | Change from baseline in glycosylated hemoglobin (HbA1c) over 26 weeks, Last Observation Carried Forward. | visit 5(week 0) and visit 14(week 26) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Change from Baseline in Insulin Resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at week 26, Last Observation Carried Forward (LOCF). The HOMA-IR is the the product of the blood Glucose and Insulin levels, divided by a constant. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/ml) × fasting plasma glucose (mmol/l) / 22.5 | [visit 5(week 0) and visit 14(week 26)] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nebivolol, Bystolic ™, Hypertension, Diabetes