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

Condition(s) targeted: Diabetes Mellitus, Type 2; Hypertension

Intervention: Carvedilol (Drug); Lisinopril (Drug); Hydrochlorothiazide (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Kaleida Health

Official(s) and/or principal investigator(s):
Paresh Dandona, MD, PhD, Principal Investigator, Affiliation: Kaleida Health / University at Buffalo

Overall contact:
Barb Hall, LPN, Phone: 716-887-5104, Email: bhall@kaleidahealth.org

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.

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

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Brachial artery vascular reactivity at 6 months

Secondary outcome:

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

Inflammatory markers and mediators at 6 months

Carotid artery intima-media thickness at 6 months

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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

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

Barb Hall, LPN, Phone: 716-887-5104, Email: bhall@kaleidahealth.org

Diabetes - Endocrinology Center of Western New York, Buffalo, New York 14209, United States

Starting date: February 2007
Ending date: May 2008
Last updated: January 30, 2007