Signaling Mechanisms and Vascular Function in Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Signaling Mechanisms and Vascular Function in Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00761852
• Other study ID #: 1999-P-003331Ruboxistaurin
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 26, 2008
• Last updated: September 29, 2008
• Start date: May 1999
• Est. completion date: October 2007

Study information

• Verified date: September 2008
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Type 1 Diabetes Mellitus
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ruboxistaurin
32 mg daily for 2 weeks
• Placebo
1 tab po QD for 2 weeks

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Eli Lilly and Company

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To test the hypothesis that activation of protein kinase Cß (PKCß) impairs vascular reactivity in patients with diabetes mellitus		one testing visit every 4 weeks for 8 weeks	No