Clinical trial NCT00430040: Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI.
Official title: Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI:Effects on Oxidative Stress and Inflammation.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Hypertension
Keywords: Type 2 Diabetes Mellitus
Hypertension
Carvedilol CR
Beta-blocker
Oxidative stress
Inflammation
Vascular benefits
Lead sponsor: University at Buffalo
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2007-02-01
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 with Carvedilol CR or lisinopril alone for 6 months and studying the effects of the drugs during this period and thereafter.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Brachial Artery Vascular Reactivity
timeFrame: 6 months
Secondary outcomes:
measure: Change in Oxidative Stress in Mononuclear Cells (MNC)
timeFrame: 6 months
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Diabetes - Endocrinology Center of Western New York
state: New York
Study officials:
affiliation: Kaleida Health / University at Buffalo
name: Paresh Dandona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: