Markers and Mechanisms of Vascular Disease in Type II Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

CSP #465D - Markers And Mechanisms of Vascular Disease in Type II Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00256646
• Other study ID #: 465D
• Status: Completed
• Phase: N/A
• First received: November 17, 2005
• Last updated: May 21, 2014
• Start date: June 2007
• Est. completion date: May 2008

Study information

• Verified date: May 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Observational

Clinical Trial 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.

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:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 298
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Observational Model: Cohort

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus
• Vascular Diseases

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Puerto Rico	VA Medical Center, San Juan	San Juan
United States	VA New Jersey Health Care System, East Orange	East Orange	New Jersey
United States	VA Central California Health Care System, Fresno	Fresno	California
United States	Edward Hines, Jr. VA Hospital	Hines	Illinois
United States	Michael E. DeBakey VA Medical Center (152)	Houston	Texas
United States	Richard Roudebush VA Medical Center, Indianapolis	Indianapolis	Indiana
United States	VA Medical Center, Lexington	Lexington	Kentucky
United States	VA Medical Center, Long Beach	Long Beach	California
United States	Miami VA Healthcare System, Miami, FL	Miami	Florida
United States	VA Medical Center, Minneapolis	Minneapolis	Minnesota
United States	VA Medical Center, Omaha	Omaha	Nebraska
United States	Carl T. Hayden VA Medical Center	Phoenix	Arizona
United States	VA Pittsburgh Health Care System	Pittsburgh	Pennsylvania
United States	VA Medical Center, Salem VA	Salem	Virginia
United States	VA South Texas Health Care System, San Antonio	San Antonio	Texas
United States	VA San Diego Healthcare System, San Diego	San Diego	California
United States	Southern Arizona VA Health Care System, Tucson	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	American Diabetes Association

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

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 di — View Citation

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.20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome measure is to define these unique processes and to elucidate underlying biochemical, metabolic, and genetic determinants of vascular disease complications in diabetes.		2, 4, and 6 years.	No