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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hypertension; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Carvedilol Controlled Release (CR); Drug: lisinopril

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14221
      • Diabetes - Endocrinology Center of Western New York

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: carvedilol	Drug: Carvedilol Controlled Release (CR); lisinopril starting dose in all patients 10 mg QD for 1 week then increase to 20 mg QD throughout the study. Initial dose: Carvedilol CR (20 mg QD, dose level 1) Titration: If tolerated, increase the dosage to 20 mg QD, 40 mg QD, and 80mg QD orally over successive intervals of at least 2 weeks to achieve target blood pressure sSBP <130 and sDBP < 80; Other Names: COREG CR; Drug: lisinopril; lisinopril starting dose in all patients 10 mg QD for 1 week then increase to 20 mg QD throughout the study; Other Names: lisinopril 10mg
Active Comparator: lisinopril	Drug: lisinopril; lisinopril starting dose in all patients 10 mg QD for 1 week then increase to 20 mg QD throughout the study; Other Names: lisinopril 10mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brachial Artery Vascular Reactivity	Percent change from baseline in Brachial artery vascular reactivity at 6 months calculated as: (brachial reactivity at 6 months-brachial reactivity at 0 months)/brachial reactivity at 0 month *100	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Oxidative Stress in Mononuclear Cells (MNC)	Percent change from baseline in Reactive Oxygen species (ROS) generation in MNC at 6 months calculated as: (ROS at 6 months-ROS at 0 months)/ROS at 0 month *100	6 months

Collaborators and Investigators

• Sponsor: University at Buffalo
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Paresh Dandona, MD, PhD, Kaleida Health / University at Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2007
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: January 30, 2007
• First Submitted That Met QC Criteria: January 30, 2007
• First Posted (Estimated): February 1, 2007

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Oxidative stress; Inflammation; Hypertension; Type 2 Diabetes Mellitus; Beta-blocker; Carvedilol CR; Vascular benefits
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Cardiotonic Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Angiotensin-Converting Enzyme Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol; Lisinopril
• Other Study ID Numbers: 1918