Signaling Mechanisms and Vascular Function in Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00761852
Recruitment Status : Completed
First Posted : September 30, 2008
Last Update Posted : September 30, 2008
Eli Lilly and Company
Information provided by:
Brigham and Women's Hospital

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

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Drug: Ruboxistaurin Drug: Placebo Phase 2 Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Signaling Mechanisms and Vascular Function in Diabetes Mellitus
Study Start Date : May 1999
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1
Drug: Ruboxistaurin
32 mg daily for 2 weeks
Other Name: LY-333531
Placebo Comparator: 2
Drug: Placebo
1 tab po QD for 2 weeks

Primary Outcome Measures :
  1. To test the hypothesis that activation of protein kinase Cß (PKCß) impairs vascular reactivity in patients with diabetes mellitus [ Time Frame: one testing visit every 4 weeks for 8 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00761852

Sponsors and Collaborators
Brigham and Women's Hospital
Eli Lilly and Company
Principal Investigator: Mark A Creager, MD Brigham and Women's Hospital

Responsible Party: Mark A. Creager, MD, Brigham and Women's Hospital Identifier: NCT00761852     History of Changes
Other Study ID Numbers: 1999-P-003331Ruboxistaurin
First Posted: September 30, 2008    Key Record Dates
Last Update Posted: September 30, 2008
Last Verified: September 2008

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action