Signaling Mechanisms and Vascular Function in Patients With Diabetes Mellitus - Full Text View

Sponsored by:	Brigham and Women's Hospital
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00762671

Purpose

The purpose of the study is to learn how blood vessel function is altered by diabetes. We are studying an investigational drug, Ebselen, to see if it can improve the ability of blood vessels to relax (widen).

Condition	Intervention	Phase
Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus	Drug: Ebselen Drug: Placebo	Phase II Phase III

MedlinePlus related topics: Diabetes Diabetes Type 1

Drug Information available for: Ebselen

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacokinetics Study
Official Title:	Signaling Mechanisms and Vascular Function in Patients With Diabetes Mellitus

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:

Endothelium-dependent and endothelium-independent vasodilation of peripheral resistance and conduit vessels will be studied in diabetic (type 1 and 2) and healthy subjects two weeks following randomization to the ebselen or placebo. [ Time Frame: one testing visit every 4 weeks ] [ Designated as safety issue: No ]

Enrollment:	60
Study Start Date:	May 1999
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
2: Placebo Comparator Placebo	Drug: Placebo Placebo 1 po BID for 2 weeks
1: Active Comparator Ebselen	Drug: Ebselen 150 mg BID for 2 weeks

Detailed Description:

A major cause of death and disability in patients with diabetes mellitus is atherosclerosis. Endothelial dysfunction is an important, if not primary, factor in atherogenesis. Nitric oxide is an important substance made and released by the endothelium. Many prior studies in animals and humans have shown that the ability of the blood vessel to dilate is impaired in diabetes. This process of vasodilation is mediated by a substance, nitric oxide, which is thought to be highly susceptible to destruction by oxidant molecules. In previous studies, we found that acute administration of the antioxidant, vitamin C, improves endothelium-dependent vasodilation in blood vessels of patients with type 1 and type 2 diabetes. This suggests that by scavenging oxidants, such as superoxide, vitamin C may reduce the destruction of nitric oxide and thereby preserve endothelial function. Additional mechanisms, including activation of a substance called protein kinase C, and oxidant stress from excess soluble peroxides may be present in diabetes and interact with oxidant stress to cause endothelial dysfunction in patients with diabetes. Accordingly, we would like to study both of these mechanisms to determine their contribution to endothelial dysfunction.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Subjects with diabetes mellitus will be eligible if they are receiving dietary treatment for hyperglycemia, sulfonylureas, metformin or insulin

Exclusion Criteria:

Any diabetic subject with a HgbA1C level of <7% or >11%
Evidence of atherosclerosis
symptoms of angina
symptoms of claudication
symptoms of cerebrovascular ischemia
findings of arterial occlusive disease, as would be suggested by decreased pulses, asymmetric blood pressure, bruits or reduced limb pressure measurements
hypertension defined as a systolic blood pressure > = 150 mmHg and a diastolic blood pressure >= 95 mmHg; (allowable blood pressure medications for diabetic subjects include calcium channel blockers, alpha and beta adrenergic blockers, and diuretics)
hypercholesterolemia, defined as total cholesterol levels greater than 75th percentile for age and sex and LDL cholesterol levels >130mg/dL.
renal insufficiency (serum creatinine >1.5 mg/dL for men; >1.2 mg/dL for women)
hepatic dysfunction defined as liver enzyme abnormalities > two times the upper limit of normal
chronic pulmonary disease
congestive heart failure
pregnancy (or subjects planning to become pregnant);
history of cigarette smoking within the last five years;
history of clinically significant coronary artery or cerebrovascular disease (defined as MI or stroke within 6 months, or presence of unstable angina)
- use of any, vasoactive, cardioactive, or non-steroidal anti-inflammatory medications within 24 hours of vascular testing visits

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00762671

Locations

United States, Massachusetts
Brigham and Women's Hosptial
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

Principal Investigator:

Mark A Creager, MD

Brigham and Women's Hosptial

More Information

No publications provided

Responsible Party:	Brigham and Women's Hospital ( Mark A. Creager, MD )
Study ID Numbers:	1999-P-003331Ebselen
Study First Received:	September 26, 2008
Last Updated:	September 29, 2008
ClinicalTrials.gov Identifier:	NCT00762671 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Diabetes Mellitus

Endocrine System Diseases
Diabetes Mellitus Type 1
Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder

Additional relevant MeSH terms:

Autoimmune Diseases
Metabolic Diseases
Immune System Diseases
Diabetes Mellitus, Type 1

Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on May 07, 2009