Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus - Full Text View

Sponsors and Collaborators:	Vanderbilt University National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00829699

Purpose

The purpose of this study is to learn more about why patients with diabetes have increased heart attacks, strokes and other illnesses due to blood clots causing blockage of a blood vessel. The proposed protocol will study the separate and combined effects of hyperglycemia and hypertriglyceridemia on endothelial function and fibrinolytic balance in Type 2 DM. Our hypothesis is that 1)combined hyperglycemia and hyperlipidemia will cause a greater impairment of vascular fibrinolytic balance than either alone; and 2)increased insulin will help to improve the alteration of fibrinolytic balance.

Condition	Intervention
Type 2 Diabetes	Procedure: euinsulinemic euglycemic glucose clamp Procedure: euinsulinemic hyperglycemic glucose clamp Procedure: Hyperinsulinemic euglycemic glucose clamp Procedure: Hyperinsulinemic hyperglycemic glucose clamp

MedlinePlus related topics: Diabetes

Drug Information available for: Dextrose

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Single Blind (Subject), Active Control, Factorial Assignment
Official Title:	Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus, Question 3

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Flow mediated dilation of brachial artery [ Time Frame: 4 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Lipid measures [ Time Frame: 4hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	April 2009
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Euinsulinemic Euglycemic glucose clamp with lipid infusion	Procedure: euinsulinemic euglycemic glucose clamp euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours
2: Experimental Euinsulinemic Hyperglycemic glucose clamp with lipid infusion	Procedure: euinsulinemic hyperglycemic glucose clamp euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
3: Experimental Hyperinsulinemic euglycemic glucose clamp with lipid infusion	Procedure: Hyperinsulinemic euglycemic glucose clamp Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
4: Experimental Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion	Procedure: Hyperinsulinemic hyperglycemic glucose clamp Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

Detailed Description:

Currently 75-80% of diabetes mellitus (DM) patients die due to thrombotic causes. Data from the Centers for Disease Control and Prevention released in 2000 indicated that mortality due to coronary artery disease is decreasing except in individuals with diabetes. Clearly the disordered metabolism, which includes abnormal metabolism of lipids resulting in higher triglyceride and free fatty acid blood levels, occurring in diabetes predisposes these individuals to increased thrombotic events. Unless the underlying mechanisms responsible for these events can be identified, there will be an unprecedented number of diabetic patients suffering thrombotic episodes in the next 10 years.

The specific aims of this study are to determine the effects of elevated free fatty acids and hyperglycemia on endothelial function and thrombolytic balance in patients with type 2 diabetes, and to determine the effects of increased insulin in this setting.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

16 Type 2 diabetic patients age >18 yrs
16 Non-diabetic controls age and weight matched
Body mass index >20 kg/m2
Female volunteers of childbearing potential: negative HCG pregnancy test
Volunteers over 40 years old: an ECG with no clinically significant conduction or ischemic changes.
For those with type 2 diabetes: HBA1C > 5.5%
For those with type 2 diabetes: C-peptide >0.2 nmol, If C-peptide is abnormal or there is a clinical suspicion for type 1 diabetes, MODY or LADA, anti-islet cell and anti-GAD 65 and 67 antibodies will be assessed to establish the diagnosis of type 2 diabetes vs. type 1/LADA/MODY.
Repeat screening labs (CBC, basic metabolic panel, liver function tests, triglycerides, PT/INR and PTT) will be checked every 6 months or at the next study visit after the 6 month expiration of the screening labs in all volunteers
Patients with diabetes will have a repeat hemoglobin A1c at study visits 2, 3, and 4.
Patients with diabetes will have had a glucose >50mg/dl and <400mg/dl during overnight control prior to starting the glucose clamp.

Exclusion Criteria:

Any current disease condition that alters carbohydrate metabolism (other than type 2 DM) and/or evidence for clinically significant cardiac disease
Uncontrolled hypertension
Pregnancy
Subjects unable to give voluntary informed consent
Subjects with history of pancreatitis
Subjects with known liver or kidney disease
Subjects on anticoagulant drugs, anemic, or with known bleeding diseases
Subjects with history of GI bleeding requiring treatment
Tobacco Use
Subjects with history of heparin-induced thrombocytopenia or heparin allergy
Subjects with severe egg or legume (soybean) allergy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00829699

Contacts

Contact: Michelle Griffith, MD	615-936-1824	michelle.griffith@vanderbilt.edu
Contact: Donna Tate	615-936-1824	donna.tate@vanderbilt.edu

Locations

United States, Tennessee
Vanderbilt Univerisity
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Stephen N. Davis, MD

Vanderbilt University

More Information

No publications provided

Responsible Party:	Vanderbilt University ( Stephen N. Davis )
Study ID Numbers:	IRB #081292, RFAHL04016
Study First Received:	January 23, 2009
Last Updated:	March 4, 2009
ClinicalTrials.gov Identifier:	NCT00829699 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

endothelial function
fibrinolytic balance

Study placed in the following topic categories:

Embolism and Thrombosis
Metabolic Diseases
Embolism
Diabetes Mellitus, Type 2
Vascular Diseases
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder
Thrombosis

Additional relevant MeSH terms:

Embolism and Thrombosis
Metabolic Diseases
Diabetes Mellitus, Type 2
Vascular Diseases
Diabetes Mellitus

Endocrine System Diseases
Cardiovascular Diseases
Glucose Metabolism Disorders
Thrombosis

ClinicalTrials.gov processed this record on May 07, 2009