Signaling Mechanisms and Vascular Function in Diabetes Mellitus

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00761852
First received: September 26, 2008
Last updated: September 29, 2008
Last verified: September 2008

September 26, 2008
September 29, 2008
May 1999
October 2007   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00761852 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
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Signaling Mechanisms and Vascular Function in Diabetes Mellitus
Signaling Mechanisms and Vascular Function in Diabetes Mellitus

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

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
  • Type 1 Diabetes Mellitus
  • Type 2 Diabetes Mellitus
  • Drug: Ruboxistaurin
    32 mg daily for 2 weeks
    Other Name: LY-333531
  • Drug: Placebo
    1 tab po QD for 2 weeks
  • Active Comparator: 1
    Ruboxistaurin
    Intervention: Drug: Ruboxistaurin
  • Placebo Comparator: 2
    Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
October 2007
October 2007   (final data collection date for primary outcome measure)

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
Both
18 Years to 85 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00761852
1999-P-003331Ruboxistaurin
Yes
Mark A. Creager, MD, Brigham and Women's Hospital
Brigham and Women's Hospital
Eli Lilly and Company
Principal Investigator: Mark A Creager, MD Brigham and Women's Hospital
Brigham and Women's Hospital
September 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP