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Signaling Mechanisms and Vascular Function in Diabetes Mellitus

Primary Purpose

Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Ruboxistaurin

Placebo

About this trial

This is an interventional basic science trial for Type 1 Diabetes Mellitus

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

Ruboxistaurin

Placebo

Outcomes

Primary Outcome Measures

To test the hypothesis that activation of protein kinase Cß (PKCß) impairs vascular reactivity in patients with diabetes mellitus

Secondary Outcome Measures

Full Information

NCT ID

NCT00761852

First Posted

September 26, 2008

Last Updated

September 29, 2008

Sponsor

Brigham and Women's Hospital

Collaborators

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00761852

Brief Title

Signaling Mechanisms and Vascular Function in Diabetes Mellitus

Official Title

Signaling Mechanisms and Vascular Function in Diabetes Mellitus

Study Type

Interventional

2. Study Status

Record Verification Date

September 2008

Overall Recruitment Status

Completed

Study Start Date

May 1999 (undefined)

Primary Completion Date

October 2007 (Actual)

Study Completion Date

October 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Brigham and Women's Hospital

Collaborators

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2, Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Ruboxistaurin

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Ruboxistaurin

Other Intervention Name(s)

LY-333531

Intervention Description

32 mg daily for 2 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

1 tab po QD for 2 weeks

Primary Outcome Measure Information:

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark A Creager, MD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

12. IPD Sharing Statement

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Signaling Mechanisms and Vascular Function in Diabetes Mellitus

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