The Vascular Effects of Carvedilol Controlled Release (CR) in Abdominally Obese Hypertensive Patients

NCT ID: NCT00459056

Last Updated: 2013-12-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2010-05-31

Brief Summary

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The purpose of this study is to compare the effects of two different combination therapies for high blood pressure on vascular health.

Detailed Description

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Hydrochlorothiazide (HCTZ) has been a popular choice for the treatment of hypertension mainly due to its efficacy in lowering blood pressure, safety, and cost-effectiveness. Similarly, angiotensin converting enzyme inhibitors (ACE-I), because of their neutral to positive impact on glycemic control, have been a popular choice for addressing hypertension in abdominally obese patients. Furthermore, the ACE-I drug class has been shown to improve vascular endothelial function and inflammation in addition to its blood pressure lowering effects.

Conversely, beta-adrenergic receptor blockers (b-blockers) have generally been avoided as first line anti-hypertensive therapy in pre-diabetic patients due to concerns about worsening glycemic control and potential hastening of progression to type 2 diabetes mellitus (T2DM). However, recent data have shown that the 3rd generation b-blocker carvedilol does not negatively affect glucose metabolism and therefore may be a safe and effective choice for blood pressure control in these patients. This neutral glycemic effect is likely due to the fact that carvedilol is a non-selective b-receptor antagonist (blocks both b1 and b2 receptors) with alpha1-receptor blocking properties. In addition, carvedilol possesses anti-oxidant properties and improves endothelial function, potentially making it an attractive anti-hypertensive treatment strategy in patients with abdominal obesity.

The combination of carvedilol and lisinopril may be especially effective in reducing blood pressure and may act synergistically to address the impaired vascular function and increased inflammation and oxidative stress present in patients with the metabolic syndrome phenotype. Therefore the primary objective of the current study will be to evaluate the effects of carvedilol CR + lisinopril compared to lisinopril + HCTZ on vascular function in a head to head trial in abdominally obese, hypertensive patients. The secondary objective will be to compare the effects of these two anti-hypertensive therapies on plasma biomarkers of endothelial activation, inflammation, and oxidative stress in these patients.

Conditions

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Abdominal Obesity Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Carvediolol CR + Lisinopril, then Lisinopril + HCTZ

Subjects were randomly assigned to Carvedilol CR + Lisinopril for three months, then had a washout period of one month, and then were given Lisinopril + HCTZ for the final three months.

Group Type EXPERIMENTAL

Carvedilol CR + Lisinopril

Intervention Type DRUG

Participants were given Carvedilol CR + Lisinopril for three months. Oral medication. Carvedilol CR and Lisinopril combination therapy was initiated at 20 mg and 10 mg, respectively. Patients returned one week later and doses of carvedilol CR and lisinopril were increased to 40 mg and 20 mg, respectively, depending on blood pressure.

Lisinopril + HCTZ

Intervention Type DRUG

Participants were given Lisinopril + HCTZ for three months. Oral medication. Lisinopril + HCTZ combination therapy was initiated at 12.5 mg and 10 mg, respectively. Patients returned 1 week later and doses of hydrochlorothiazide and lisinopril were increased to 25 mg and 20 mg, respectively, depending on blood pressure levels.

Lisinopril + HCTZ, then Carvedilol CR + Lisinopril

Subjects were randomally assigned to Lisinopril + HCTZ for three months, then had a washout period for one month, and then were given Carvedilol CR + Lisinopril for the final three months.

Group Type ACTIVE_COMPARATOR

Carvedilol CR + Lisinopril

Intervention Type DRUG

Participants were given Carvedilol CR + Lisinopril for three months. Oral medication. Carvedilol CR and Lisinopril combination therapy was initiated at 20 mg and 10 mg, respectively. Patients returned one week later and doses of carvedilol CR and lisinopril were increased to 40 mg and 20 mg, respectively, depending on blood pressure.

Lisinopril + HCTZ

Intervention Type DRUG

Participants were given Lisinopril + HCTZ for three months. Oral medication. Lisinopril + HCTZ combination therapy was initiated at 12.5 mg and 10 mg, respectively. Patients returned 1 week later and doses of hydrochlorothiazide and lisinopril were increased to 25 mg and 20 mg, respectively, depending on blood pressure levels.

Interventions

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Carvedilol CR + Lisinopril

Participants were given Carvedilol CR + Lisinopril for three months. Oral medication. Carvedilol CR and Lisinopril combination therapy was initiated at 20 mg and 10 mg, respectively. Patients returned one week later and doses of carvedilol CR and lisinopril were increased to 40 mg and 20 mg, respectively, depending on blood pressure.

Intervention Type DRUG

Lisinopril + HCTZ

Participants were given Lisinopril + HCTZ for three months. Oral medication. Lisinopril + HCTZ combination therapy was initiated at 12.5 mg and 10 mg, respectively. Patients returned 1 week later and doses of hydrochlorothiazide and lisinopril were increased to 25 mg and 20 mg, respectively, depending on blood pressure levels.

Intervention Type DRUG

Other Intervention Names

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Prinivil Coreg Prinivil Hydrochlorothiazide

Eligibility Criteria

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Inclusion Criteria

* \>18 years old
* Systolic blood pressure (SBP) \>130 and/or diastolic blood pressure (DBP) \>85 (or currently taking anti-hypertensive medication)
* Waist circumference \>102 cm (men) and \>88 cm (women)
* Stable cardiovascular medication regimen (or other medications known to affect endothelial function) at least 1 month prior to enrollment and throughout the study

Exclusion Criteria

* Use of anti-hypertensive medications within one month of randomization (patients may be washed-out from anti-hypertensive medications)
* Unstable angina
* History of angina symptoms within 3 months of screening
* Decompensated heart failure
* History of myocardial infarction
* Stroke or coronary artery bypass graft within 3 months of screening
* Standard clinical contraindications to beta-blocker therapy
* Standard clinical contraindications to ACE-I therapy
* Women who are currently pregnant or planning to become pregnant (pregnancy testing will occur at specific intervals throughout study and women will be informed of potential risks during the consenting process; information specific to this risk will be detailed in the consent form)
* Breastfeeding women
* Clinically significant liver disease
* Creatinine \> 2.5 mg/dL
* Hepatic function greater than 3 times upper limit of normal
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

St. Paul Heart Clinic

OTHER

Sponsor Role lead

Responsible Party

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Aaron S. Kelly, Ph.D.

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Aaron S Kelly, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Paul Heart Clinic

Locations

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St. Paul Heart Clinic

Saint Paul, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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SPHC 2007-01

Identifier Type: -

Identifier Source: org_study_id