Markers and Mechanisms of Vascular Disease in Type II Diabetes
Information source: Department of Veterans Affairs
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes Mellitus
Intervention: Insulin (Drug); Glimepiride (Drug); Rosiglitazone (Drug); Metformin (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Department of Veterans Affairs Official(s) and/or principal investigator(s):
Maria Lopes-Virella, MD, Principal Investigator, Affiliation: Charleston VAMC
Carlos Abraira, MD, Study Chair, Affiliation: Miami VAMC
William Duckworth, MD, Study Chair, Affiliation: Phoenix VAMC
Summary
OBJECTIVES: Vascular Disease is the leading cause of complications and death in patients
with diabetes. Risk markers and underlying mechanisms have not been fully elucidated, and
may differ from those in non-diabetic individuals. The unifying theme for the Program
Project is that hyperglycemia and insulin resistance alter a number of biological processes
which interact in vicious cycles to accelerate atherogenesis and are consequently major
underlying risk factors for vascular disease. The overall objectives are to define these
unique processes and to elucidate underlying biochemical, metabolic, and genetic determinants
of vascular disease complications in diabetes.
RESEARCH PLAN: Over the past 4 years, we have collaborated with the DCCT/EDIC Study Group,
and have made novel observations regarding vascular disease pathogenesis in Type 1 Diabetes.
This work has focused our studies on specific pathogenic processes. We will now study a Type
2 Diabetes cohort from the VA Cooperative Study, "Glycemic Control and the Complications of
Diabetes, Type 2", with high vascular disease event rates. These collaborations provide a
unique opportunity to address the pathogenesis of accelerated atherogenesis in the two main
types of diabetes, and will greatly augment the scientific knowledge that will be gained in
the conduct of these world-class prospective trials.
METHODS: The Program Project has 4 projects and 3 cores. Project 1 will assess lipoproteins,
glycoxidative stress, and inflammation as risk factors in studies involving Type 2 Diabetes
patients and cultured cell systems. Based on preliminary data from our initial studies Type
1 patients, changes in the NMR lipoprotein subclass profile will be emphasized.
Project 2 will elucidate interactions between inflammation, modifications of lipoproteins,
and autoimmunity in vascular disease risk. These novel concepts are also based upon exciting
preliminary data pertaining to LDL-antibody complexes.
Project 3 will pursue interesting preliminary data and define the role of the
kallikrein-kinin system in vascular disease complications, with effects on mitogenesis and
matrix production.
Project 4 will assess the role of the Insulin Resistance Syndrome and novel factors secreted
from adipocytes in the pathophysiology of biochemical risk factors and cardiovascular
complications.
Cores include an Administrative Core, a Biostatistics and Epidemiology Core which will link
with the trials data coordinating centers, and Molecular and Statistical Genetics Core.
Investigators will work in close collaboration with the VA Executive Committee, Study
Centers, the Hines Coordinating Center, and some of the other ancillary studies. All data
analysis involving clinical outcomes will be performed at the Hines Coordinating Center.
There is true synergism among the projects at both scientific and logistical levels. The
Program Project design allows for interactions among multidisciplinary investigators studying
the same cohort, which will define how multiple pathological processes interact at the level
of the arterial wall to promote atherosclerosis.
Clinical Details
Official title: CSP #465-D - MARKERS AND MECHANISMS OF VASCULAR DISEASE IN TYPE II DIABETES
Study design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Detailed description:
Primary Hypothesis:
Secondary Hypotheses:
Primary Outcomes:
Study Abstract:
OBJECTIVES: Vascular Disease is the leading cause of complications and death in patients
with diabetes. Risk markers and underlying mechanisms have not been fully elucidated, and
may differ from those in non-diabetic individuals. The unifying theme for the Program
Project is that hyperglycemia and insulin resistance alter a number of biological processes
which interact in vicious cycles to accelerate atherogenesis and are consequently major
underlying risk factors for vascular disease. The overall objectives are to define these
unique processes and to elucidate underlying biochemical, metabolic, and genetic determinants
of vascular disease complications in diabetes.
RESEARCH PLAN: Over the past 4 years, we have collaborated with the DCCT/EDIC Study Group,
and have made novel observations regarding vascular disease pathogenesis in Type 1 Diabetes.
This work has focused our studies on specific pathogenic processes. We will now study a Type
2 Diabetes cohort from the VA Cooperative Study, "Glycemic Control and the Complications of
Diabetes, Type 2", with high vascular disease event rates. These collaborations provide a
unique opportunity to address the pathogenesis of accelerated atherogenesis in the two main
types of diabetes, and will greatly augment the scientific knowledge that will be gained in
the conduct of these world-class prospective trials.
METHODS: The Program Project has 4 projects and 3 cores. Project 1 will assess lipoproteins,
glycoxidative stress, and inflammation as risk factors in studies involving Type 2 Diabetes
patients and cultured cell systems. Based on preliminary data from our initial studies Type
1 patients, changes in the NMR lipoprotein subclass profile will be emphasized.
Project 2 will elucidate interactions between inflammation, modifications of lipoproteins,
and autoimmunity in vascular disease risk. These novel concepts are also based upon exciting
preliminary data pertaining to LDL-antibody complexes.
Project 3 will pursue interesting preliminary data and define the role of the
kallikrein-kinin system in vascular disease complications, with effects on mitogenesis and
matrix production.
Project 4 will assess the role of the Insulin Resistance Syndrome and novel factors secreted
from adipocytes in the pathophysiology of biochemical risk factors and cardiovascular
complications.
Cores include an Administrative Core, a Biostatistics and Epidemiology Core which will link
with the trials data coordinating centers, and Molecular and Statistical Genetics Core.
Investigators will work in close collaboration with the VA Executive Committee, Study
Centers, the Hines Coordinating Center, and some of the other ancillary studies. All data
analysis involving clinical outcomes will be performed at the Hines Coordinating Center.
There is true synergism among the projects at both scientific and logistical levels. The
Program Project design allows for interactions among multidisciplinary investigators studying
the same cohort, which will define how multiple pathological processes interact at the level
of the arterial wall to promote atherosclerosis.
Main Manuscript:
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Patients with type 2 DM who are no longer responsive to maximum dose of one or more oral
agents
Locations and Contacts
Vamc - San Juan, Pr, San Juan 00921, Puerto Rico
Vamc - Tucson, Az, Tucson, Arizona 85723, United States
Vamc - Phoenix, Az, Phoenix, Arizona 85012, United States
Va Medical Center - Fresno, Fresno, California 93703, United States
Vamc - San Diego, Ca, San Diego, California 92161, United States
Long Beach Vamc, Long Beach, California 90822, United States
Vamc - Miami, Fl, Miami, Florida 33125, United States
HINES VAMC, Hines, Illinois 60141, United States
Vamc - Indianapolis, in, Indianapolis, Indiana 46202, United States
Vamc - Lexington, Ky, Lexington, Kentucky 40511-1093, United States
Vamc - Minneapolis, Mn, Minneapolis, Minnesota 55417, United States
Vamc - Omaha, Ne, Omaha, Nebraska 68105, United States
Va New Jersey Healthcare System, Lyons, New Jersey 07939, United States
Vamc - Pittsburgh, Pa, Pittsburgh, Pennsylvania 15261, United States
Vamc - San Antonio, Tx, San Antonio, Texas 78284, United States
Houston Vamc, Houston, Texas 77030-2498, United States
Salem Va Medical Center, Salem, Virginia 24153, United States
Additional Information
Ending date: November 2007
Last updated: June 4, 2007
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