Markers and Mechanisms of Vascular Disease in Type II Diabetes

NCT ID: NCT00256646

Last Updated: 2014-05-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

298 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-06-30

Study Completion Date

2008-05-31

Brief Summary

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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.

Detailed Description

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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:

There is no independent data for this study, it was part of a larger study. Therefore there will be no results for this record/study.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Observational Model Type

COHORT

Study Groups

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Group 1

Patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2".

Rosiglitazone

Intervention Type DRUG

ROSIGLITAZONE (roe si GLI ta zone) helps to treat type 2 diabetes. It helps to control blood sugar. Treatment is combined with diet and exercise.

Interventions

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Rosiglitazone

ROSIGLITAZONE (roe si GLI ta zone) helps to treat type 2 diabetes. It helps to control blood sugar. Treatment is combined with diet and exercise.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Patients with type 2 DM who are no longer responsive to maximum dose of one or more oral agents

Exclusion Criteria

Patients that did not participate in the VADT.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American Diabetes Association

OTHER

Sponsor Role collaborator

US Department of Veterans Affairs

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carlos Abraira, MD

Role: STUDY_CHAIR

Miami VA Healthcare System, Miami, FL

Locations

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Carl T. Hayden VA Medical Center

Phoenix, Arizona, United States

Site Status

Southern Arizona VA Health Care System, Tucson

Tucson, Arizona, United States

Site Status

VA Central California Health Care System, Fresno

Fresno, California, United States

Site Status

VA Medical Center, Long Beach

Long Beach, California, United States

Site Status

VA San Diego Healthcare System, San Diego

San Diego, California, United States

Site Status

Miami VA Healthcare System, Miami, FL

Miami, Florida, United States

Site Status

Edward Hines, Jr. VA Hospital

Hines, Illinois, United States

Site Status

Richard Roudebush VA Medical Center, Indianapolis

Indianapolis, Indiana, United States

Site Status

VA Medical Center, Lexington

Lexington, Kentucky, United States

Site Status

VA Medical Center, Minneapolis

Minneapolis, Minnesota, United States

Site Status

VA Medical Center, Omaha

Omaha, Nebraska, United States

Site Status

VA New Jersey Health Care System, East Orange

East Orange, New Jersey, United States

Site Status

VA Pittsburgh Health Care System

Pittsburgh, Pennsylvania, United States

Site Status

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, United States

Site Status

VA South Texas Health Care System, San Antonio

San Antonio, Texas, United States

Site Status

VA Medical Center, Salem VA

Salem, Virginia, United States

Site Status

VA Medical Center, San Juan

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Lopes-Virella MF, Hunt KJ, Baker NL, Virella G, Moritz T; VADT Investigators. The levels of MDA-LDL in circulating immune complexes predict myocardial infarction in the VADT study. Atherosclerosis. 2012 Oct;224(2):526-31. doi: 10.1016/j.atherosclerosis.2012.08.006. Epub 2012 Aug 21.

Reference Type RESULT
PMID: 22963984 (View on PubMed)

Bhensdadia NM, Hunt KJ, Lopes-Virella MF, Michael Tucker J, Mataria MR, Alge JL, Neely BA, Janech MG, Arthur JM; Veterans Affairs Diabetes Trial (VADT) study group. Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes. Kidney Int. 2013 Jun;83(6):1136-43. doi: 10.1038/ki.2013.57. Epub 2013 Mar 27.

Reference Type RESULT
PMID: 23536133 (View on PubMed)

Other Identifiers

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465D

Identifier Type: -

Identifier Source: org_study_id

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