Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI.

Sponsor

University at Buffalo (Other)

Overall Status

Terminated

CT.gov ID

NCT00430040

Collaborator

GlaxoSmithKline (Industry)

Enrollment

Location

Arms

74.9

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine whether addition of Carvedilol CR to diabetic patients with hypertension who are receiving the ACEi,Lisinopril,will provide added benefits to blood vessels when compared to treatment with Lisinopril alone.It is believed that carvedilol provides added benefits by suppressing free radicals(charged substances that cause damage to the body ) and inflammation.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 Hypertension	Drug: carvedilol Drug: lisinopril	Phase 4

Detailed Description

Type 2 diabetes is an atherosclerotic, pro-inflammatory and pro-oxidative stress.Both vascular oxidative stress and inflammation are CVD risk factors and impact endothelial function.

Carvedilol has been demonstrated in preclinical and clinical studies (although limited in size) to exert anti-inflammatory and antioxidant properties: (1) reduce the inflammation markers such as high sensitivity C-reactive protein (hsCRP); (2) reduce oxidative stress via dually eliminating existing reactive oxygen species (ROS) and suppressing the generation of ROS; (3) prevent lipid peroxidation in myocardial cell membrane; (4) protect endothelial and vascular muscle cells from oxygen radical-mediated injury.

This project is about studying the effect of carvedilol CR on blood vessels of diabetic hypertensive patients as compared to Lisinopril alone.

This study involves weaning patient off their current antihypertensive medications and starting them on Lisinopril and Carvedilol CR or placebo for 6 months and studying the effects of the drugs during this period and thereafter.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI:Effects on Oxidative Stress and Inflammation.

Actual Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: carvedilol carvedilol	Drug: carvedilol carvedilol
Active Comparator: lisinopril lisinopril	Drug: lisinopril lisinopril

Arm

Intervention/Treatment

Experimental: carvedilol

carvedilol

Drug: carvedilol

carvedilol

Active Comparator: lisinopril

lisinopril

Drug: lisinopril

lisinopril

Outcome Measures

Primary Outcome Measures

Brachial artery vascular reactivity at 6 months [6 months]
Brachial artery vascular reactivity

Secondary Outcome Measures

Oxidative stress in Mononuclear cells, serum and plasma at six months [6 months]
Oxidative stress

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Is male or female >= 18 and <= 70 years of age
Has a documented history of type 2 diabetes mellitus for a minimum of four months prior to the screening visit
Has a documented history of or current presentation with Stage 1 or Stage 2 hypertension and meets one of the following criteria:
Has controlled hypertension (sSBP <130 mmHg AND sDBP <80 mmHg) on >=2 antihypertensive medications NOTE: A combination drug containing two antihypertensive agents represents two antihypertensive medications OR
Has uncontrolled hypertension (sSBP >=130 and <=170 mmHg AND/OR sDBP >=80 and <=105 mmHg) on one or two antihypertensive medications OR
Has newly diagnosed or previously untreated hypertension (sSBP >=130 and <=170 mmHg AND/OR sDBP >=80 and <=105 mmHg
At Randomization, sitting systolic blood pressure (sSBP) >= 130 mmHg or sitting diastolic blood pressure (sDBP) >= 80 mmHg and sSBP <= 170 mmHg and sDBP <= 105 mmHg
Has been on a stable dose of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) for a minimum of four months prior to the screening visit

Exclusion Criteria:

Has any clinically significant abnormality identified in the screening physical examination, laboratory tests or electrocardiogram which, in the judgement of the investigator, would preclude safe completion of the study
Is female of childbearing potential
Has any of these cardiac conditions: uncontrollable or symptomatic arrhythmias, unstable angina, sick sinus syndrome or second or third degree heart block (unless treated with a permanent, functioning pacemaker), bradycardia (heart rate <55 bpm), and stroke within three months of study screening, and history of myocardial infarction.
Has Congestive Heart Failure NYHA (New York Heart Association) class II-IV
Has type 1 diabetes mellitus
Has newly diagnosed type 2 diabetes (within 4 months of screening visit)
Has HbA1c > 8.5%
Has the following, as it relates to subject's antidiabetic therapy:Initiated or changed dosage or formulation of thiazolidinediones (TZDs) within 6 months of screening visit.
A history of acute or chronic acidosis, including diabetic ketoacidosis
Has current clinical diagnosis of chronic obstructive pulmonary disease (COPD, e.g., chronic bronchitis) or asthma
Has a history of bronchospastic disease not undergoing active therapy in whom, in the investigator's opinion, treatment with study medication could provoke bronchospasm
Has evidence of any of the following clinically significant diseases that could impair the absorption, metabolism, or excretion of orally-administered medication:
renal disease defined as estimated Glomerular Filtration Rate (eGFR) <60mL/min per 1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula below: GFR (mL/min/1.73m2) = 186 x [Serum Creatinine (umol/L) x 0.0113]-1.154 x Age(years)-0.203 (x 0.742 if female)
hepatic disease (i.e., ALT or AST levels greater than three times the upper limit of normal range, history of hepatic impairment, or by clinical assessment)
Chronic biliary disorders
Has endocrine disorders (e.g., pheochromocytoma, active and untreated hypo or hyperthyroidism)
Has any known contraindication to ACE inhibitors, alpha- or beta-blocker treatment
Has systemic disease, including cancer, with reduced (<12 months) life expectancy
Has used an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication
Has a history of a psychological illness or any condition that would interfere with the subject's ability to understand or complete the requirements of the study