Non-traditional Cardiovascular Risk Factors and Atherosclerosis in Type 2 Diabetes
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First Received Date ICMJE | November 17, 2005 | ||||
Last Updated Date | February 7, 2012 | ||||
Start Date ICMJE | June 2007 | ||||
Primary Completion Date | May 2008 (final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
1) Determine the cross-sectional relationship between baseline levels of novel CVRF and the [ Time Frame: 3 to 5 years ] [ Designated as safety issue: No ] | ||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | Complete list of historical versions of study NCT00256607 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures ICMJE | |||||
Original Secondary Outcome Measures ICMJE | |||||
Current Other Outcome Measures ICMJE | |||||
Original Other Outcome Measures ICMJE | |||||
Descriptive Information | |||||
Brief Title ICMJE | Non-traditional Cardiovascular Risk Factors and Atherosclerosis in Type 2 Diabetes | ||||
Official Title ICMJE | CSP #465A - Non-Traditional Cardiovascular Risk Factors And Atherosclerosis In Type 2 Diabetes | ||||
Brief Summary | A predominant consequence of diabetes mellitus (DM) type 2 is accelerated development of atherosclerosis related conditions. Conventional cardiovascular risk factors only explain a portion of the excess risk for atherosclerosis in this population. In vitro, animal and epidemiologic studies have suggested that a variety of "novel" cardiovascular risk factors (CVRF), including triglyceride-rich lipoproteins (TGRL), small dense low density lipoprotein (D-LDL) subfractions, oxidative stress, and advanced glycation endproduct (AGE) formation may contribute to the development of atherosclerosis. These risk factors may also induce endothelial cell activation/injury or local or systemic inflammation that cause elevations in plasma levels of additional novel risk factors, such as soluble adhesion molecules, plasminogen activator inhibitor-1 (PAI-1), fibrinogen and C-reactive protein (CRP). Many of these risk factors are increased in DM type 2, presumably as a consequence of hyperglycemia and insulin resistance. However, no studies have evaluated the singular or synergistic relationship of these novel (CVRF) to measures of atherosclerosis as well as to the development of clinical macrovascular events in individuals with diabetes. If, as we suspect, these novel CVRF are related to development of atherosclerosis and macrovascular disease, it will be critical for the future design of prevention strategies to know whether intensive glucose lowering significantly reduces the levels of these novel CVRF. Furthermore, it would be important to explore whether the relationship of the above novel risk factors to atherosclerosis and development of clinical events is attenuated in those individuals receiving glucose lowering therapy. Alternatively, if glucose lowering has no effect (or a negative effect), on relevant novel CVRF, this could potentially explain the limited success of intensive glucose lowering to reduce macrovascular events in several prior trials. The investigator proposes to take advantage of the study population and framework of the recently approved VA Cooperative Study of "Glycemic Control and Complications in Diabetes Mellitus Type 2" to address these issues in an efficient and cost-effective manner. |
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Detailed Description | Primary Hypothesis:Hypothesis The novel CVRF including the selected indicators of artery wall injury and local or systemic inflammation, are related to the presence and development of atherosclerosis and macrovascular events in DM type 2. 2.Intensive glucose lowering therapy will reduce the levels of several, if not all, of the novel CVRF. Secondary Hypotheses: Primary Outcomes:
Study Abstract: Objectives A predominant consequence of diabetes mellitus (DM) type 2 is accelerated development of atherosclerosis related conditions. Conventional cardiovascular risk factors only explain a portion of the excess risk for atherosclerosis in this population. In vitro, animal and epidemiologic studies have suggested that a variety of "novel" cardiovascular risk factors (CVRF), including triglyceride-rich lipoproteins (TGRL), small dense low density lipoprotein (D-LDL) subfractions, oxidative stress, and advanced glycation endproduct (AGE) formation may contribute to the development of atherosclerosis. These risk factors may also induce endothelial cell activation/injury or local or systemic inflammation that cause elevations in plasma levels of additional novel risk factors, such as soluble adhesion molecules, plasminogen activator inhibitor-1 (PAI-1), fibrinogen and C-reactive protein (CRP). Many of these risk factors are increased in DM type 2, presumably as a consequence of hyperglycemia and insulin resistance. However, no studies have evaluated the singular or synergistic relationship of these novel (CVRF) to measures of atherosclerosis as well as to the development of clinical macrovascular events in individuals with diabetes. If, as we suspect, these novel CVRF are related to development of atherosclerosis and macrovascular disease, it will be critical for the future design of prevention strategies to know whether intensive glucose lowering significantly reduces the levels of these novel CVRF. Furthermore, it would be important to explore whether the relationship of the above novel risk factors to atherosclerosis and development of clinical events is attenuated in those individuals receiving glucose lowering therapy. Alternatively, if glucose lowering has no effect (or a negative effect), on relevant novel CVRF, this could potentially explain the limited success of intensive glucose lowering to reduce macrovascular events in several prior trials. The investigator proposes to take advantage of the study population and framework of the recently approved VA Cooperative Study of "Glycemic Control and Complications in Diabetes Mellitus Type 2" to address these issues in an efficient and cost-effective manner. Hypothesis
Research Plan Specific objectives 1& 2: Cross-sectional observational objectives
Specific objective 3: Prospective interventional objective Determine whether intensive glucose lowering reduces levels of novel CVRF. Future long-term specific objectives: Prospective observational objectives
Main Manuscript: |
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Study Type ICMJE | Observational | ||||
Study Design ICMJE | Observational Model: Cohort Time Perspective: Prospective |
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Biospecimen | |||||
Sampling Method | Non-Probability Sample | ||||
Study Population | This observational study of patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2@ |
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Condition ICMJE | Type 2 Diabetes Mellitus | ||||
Intervention ICMJE |
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Study Group/Cohort (s) | 1
Cohort from the VADT study.
Interventions:
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Enrollment ICMJE | 317 | ||||
Completion Date | May 2008 | ||||
Primary Completion Date | May 2008 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | 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 have not paricipated in the VADT. |
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Gender | Both | ||||
Ages | 40 Years and older | ||||
Accepts Healthy Volunteers | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Location Countries ICMJE | United States | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT00256607 | ||||
Other Study ID Numbers ICMJE | 465A | ||||
Has Data Monitoring Committee | Yes | ||||
Responsible Party | Department of Veterans Affairs | ||||
Study Sponsor ICMJE | Department of Veterans Affairs | ||||
Collaborators ICMJE | |||||
Investigators ICMJE |
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Information Provided By | Department of Veterans Affairs | ||||
Verification Date | February 2012 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |