Correlation of Plasma Endothelial Cell Activity With Cardiovascular Events in Patients With Diabetes Mellitus Type 2

This study has been completed.
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00252525
First received: November 9, 2005
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

CSP 465-B, Correlation of Plasma Endothelial Cell (Basic Fibroblast Growth Factor) Activity With Cardiovascular Events in Patients with Diabetes Mellitus, Type II.

Mark Zimering M.D.

Objectives: Endothelial cell dysfunction plays a role in the development of the atherosclerotic vascular lesion and it is also thought to provide a mechanism for increased urinary albumin excretion in type 2 diabetes mellitus. Micro- or macroalbuminuria are associated with increased cardiovascular (CV) morbidity and mortality in type 2 diabetes mellitus. In at least one longitudinal study in older-age onset patients, micro-or macroalbuminuria robustly predicted increased CV risk independent of other diabetes-related factors.1 The pathogenetic mechanisms underlying a significant association between micro- or macroalbuminuria and CV risk in diabetes mellitus are not known but may include: growth factors, clotting factors, lipids, or hemodynamic factors. The aim of the present study is to investigate whether an angiogenic growth factor, basic fibroblast growth factor (bFGF), plays a role in increased CV risk in type 2 diabetes mellitus. Research Plan: BFGF (FGF-2) is one of the most potent known angiogenesis factors. Increased bFGF was previously associated with both endothelial cell injury and micro- or macroalbuminuria. In a prior study of 73 older-age onset veterans with type 2 diabetes mellitus (JCEM, 1996), we found plasma endothelial cell (bFGF) activity was significantly associated with glycemic levels, and (in multiple regression analysis) independently associated with both microalbuminuria and retinopathy. We will test whether plasma endothelial cell (bFGF) activity is significantly, independently associated with a pooled endpoint of cardiovascular events that includes myocardial infarction (MI), coronary revascularization, congestive heart failure (CHF), or CV mortality. We expect that increased bFGF may itself be a robust marker for increased CV risk in diabetes mellitus for three reasons. First, because bFGF was independently associated with (micro)-albuminuria in type 2 diabetes mellitus. Second, because increased bFGF was associated with increased activity in the renin-angiotensin system in vascular smooth muscle cells (Dzau, et al. JCI, 1995). And third, because (as we reported) angiotensin converting enzyme inhibitor (ACEi) drugs substantially decreased plasma bFGF levels in (micro)- albuminuric diabetes mellitus type 2, and (as others reported) ACEi drugs substantially reduced the risk of development of CHF in patients with LVH 2, the risk of mortality after MI (8,9), and the risk of CV death in diabetic patients with proteinuria.

Because plasma endothelial cell (bFGF) activity correlated significantly with glycemic levels in diabetes mellitus type 2, plasma bFGF may be one of the pathogenetic links between glycemic levels and an increased risk of cardiovascular events in diabetes mellitus, type 2.

Methods: Blood (3 mL EDTA plasma) will be collected from each subject in Years 1, and 2 of the Study at each of 6 local participating VA substudy sites. Because plasma endothelial cell (bFGF-like) bioactivity and bFGFR-IR in vivo are stable for months and years based on our prior published studies (1-3), we anticipate that obtaining 2 specimens, 1 each in Years 1, 2 of the study, will provide sufficient data to model proportional risk.


Condition
Type 2 Diabetes Mellitus

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: CSP #465B - Correlation of Plasma Endothelial Cell (Basic Fibroblast Growth Factor) Activity With Cardiovascular Events In Patients With Diabetes Mellitus Type 2

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • The primary outcome measures are cardiovascular morbidity and mortality. [ Time Frame: End of study. ] [ Designated as safety issue: No ]

Biospecimen Retention:   None Retained

The cohort consisted of patients that participated in the 465 main study.


Enrollment: 400
Study Start Date: June 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
Group 1
This is an observational study of patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2@.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

This is an observational study of patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2@.

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Not a part of the VADT.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00252525

Locations
United States, Arizona
Carl T. Hayden VA Medical Center
Phoenix, Arizona, United States, 85012
United States, California
VA Medical Center, Long Beach
Long Beach, California, United States, 90822
United States, Florida
Miami VA Healthcare System, Miami, FL
Miami, Florida, United States, 33125
United States, Nebraska
VA Medical Center, Omaha
Omaha, Nebraska, United States, 68105-1873
United States, New Jersey
VA New Jersey Health Care System, East Orange
East Orange, New Jersey, United States, 07018
United States, Texas
VA South Texas Health Care System, San Antonio
San Antonio, Texas, United States, 78229
United States, Virginia
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
American Diabetes Association
Investigators
Study Chair: Carlos Abraira, MD Miami VA Healthcare System, Miami, FL
  More Information

Publications:

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00252525     History of Changes
Other Study ID Numbers: 465B
Study First Received: November 9, 2005
Last Updated: June 26, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 30, 2014