Signaling Mechanisms and Vascular Function in Diabetes Mellitus

NCT ID: NCT00761852

Last Updated: 2008-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-05-31
• Study Completion Date: 2007-10-31

Brief Summary

Ruboxistaurin is being tested to see if it is effective in treating certain diabetic complications, such as diseases of the blood vessels.

Detailed Description

To test the hypothesis that activation of protein kinase C impairs vascular reactivity in patients with diabetes.

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.

Conditions

Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

1

Ruboxistaurin

Group Type: ACTIVE_COMPARATOR

Ruboxistaurin

Intervention Type: DRUG

32 mg daily for 2 weeks

2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1 tab po QD for 2 weeks

Interventions

Ruboxistaurin

32 mg daily for 2 weeks

Intervention Type: DRUG

Placebo

1 tab po QD for 2 weeks

Intervention Type: DRUG

Other Intervention Names

LY-333531

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Brigham and Women's Hospital

Principal Investigators

Mark A Creager, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Other Identifiers

1999-P-003331Ruboxistaurin

Identifier Type: -

Identifier Source: org_study_id