Signaling Mechanisms and Vascular Function in Patients With Diabetes Mellitus

Phase 2

Completed

• Conditions: Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: Ebselen

• Registration Number: NCT00762671
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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).

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.

Study Timeline

• Study Start: 1999-05
• Primary Completion: 2007-10
• Study Completion: 2007-10
• Status Verified: 2008-09
• Study First Submitted: 2008-09-26
• Study First Submitted QC: 2008-09-29
• Last Update Submitted: 2008-09-29
• Study First Posted: 2008-09-30
• Last Update Posted: 2008-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
2	Placebo	Placebo
1	Ebselen	Ebselen

Primary Outcome Measures

Name	Time	Method
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.	one testing visit every 4 weeks

Trial Locations

Locations (1)

Brigham and Women's Hosptial; 🇺🇸 Boston, Massachusetts, United States