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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Paresh Dandona, MD, Kaleida Health
ClinicalTrials.gov Identifier:
NCT00430040
First received: January 30, 2007
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Diabetes Mellitus, Type 2
Hypertension
Drug: carvedilol
Drug: lisinopril
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vascular Benefits of Adding CarvedilolCR to Type2 Diabetic Patients on ACEI:Effects on Oxidative Stress and Inflammation.

Resource links provided by NLM:


Further study details as provided by Kaleida Health:

Primary Outcome Measures:
  • Brachial artery vascular reactivity at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Brachial artery vascular reactivity


Secondary Outcome Measures:
  • Oxidative stress in Mononuclear cells, serum and plasma at six months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Oxidative stress


Estimated Enrollment: 60
Study Start Date: February 2007
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: carvedilol
carvedilol
Drug: carvedilol
carvedilol
Active Comparator: lisinopril
lisinopril
Drug: lisinopril
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 and Carvedilol CR or placebo for 6 months and studying the effects of the drugs during this period and thereafter.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00430040

Locations
United States, New York
Diabetes - Endocrinology Center of Western New York
Buffalo, New York, United States, 14221
Sponsors and Collaborators
Kaleida Health
GlaxoSmithKline
Investigators
Principal Investigator: Paresh Dandona, MD, PhD Kaleida Health / University at Buffalo
  More Information

Additional Information:
No publications provided

Responsible Party: Paresh Dandona, MD, MD, Kaleida Health
ClinicalTrials.gov Identifier: NCT00430040     History of Changes
Other Study ID Numbers: 1918
Study First Received: January 30, 2007
Last Updated: December 17, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Kaleida Health:
Type 2 Diabetes Mellitus
Hypertension
Carvedilol CR
Beta-blocker
Oxidative stress
Inflammation
Vascular benefits

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Carvedilol
Lisinopril
Adrenergic Agents
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic beta-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Protective Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 20, 2014