Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stephen N. Davis, University of Maryland
ClinicalTrials.gov Identifier:
NCT00829699
First received: January 23, 2009
Last updated: May 3, 2013
Last verified: May 2013

January 23, 2009
May 3, 2013
July 2009
June 2013   (final data collection date for primary outcome measure)
Percent change in flow mediated dilation of brachial artery [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
Flow mediated dilation of brachial artery [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00829699 on ClinicalTrials.gov Archive Site
Change in Lipid measures [ Time Frame: 4hours ] [ Designated as safety issue: No ]
Lipid measures [ Time Frame: 4hours ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus
Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus, Question 3

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 high glucose and high fats on certain cardiovascular responses in Type 2 DM.

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 fats 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 (high glucose)on endothelial function and thrombolytic balance in patients with type 2 diabetes, and to determine the effects of increased insulin in this setting.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Type 2 Diabetes
  • Procedure: euinsulinemic euglycemic glucose clamp
    euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours
    Other Name: Intralipid
  • Procedure: euinsulinemic hyperglycemic glucose clamp
    euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
    Other Name: Intralipid
  • Procedure: Hyperinsulinemic euglycemic glucose clamp
    Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
    Other Name: Intralipid
  • Procedure: Hyperinsulinemic hyperglycemic glucose clamp
    Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
    Other Name: Intralipid
  • Experimental: 1
    Euinsulinemic (low insulin infusion) Euglycemic (normal blood glucose levels) glucose clamp with lipid (fat) infusion
    Intervention: Procedure: euinsulinemic euglycemic glucose clamp
  • Experimental: 2
    Euinsulinemic Hyperglycemic (high glucose levels) glucose clamp with lipid infusion
    Intervention: Procedure: euinsulinemic hyperglycemic glucose clamp
  • Experimental: 3
    Hyperinsulinemic (High dose insulin) euglycemic glucose clamp with lipid infusion
    Intervention: Procedure: Hyperinsulinemic euglycemic glucose clamp
  • Experimental: 4
    Hyperinsulinemic hyperglycemic (high glucose level) glucose clamp with lipid infusion
    Intervention: Procedure: Hyperinsulinemic hyperglycemic glucose clamp
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
32
August 2013
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria

  • 16 Type 2 diabetic patients age 18 - 60 yrs
  • 16 Non-diabetic controls age 18-60 yrs
  • Body mass index >20 kg/m2
  • Female volunteers of childbearing potential: negative urine 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 antibodies will be assessed to establish the diagnosis of type 2 diabetes vs. type 1/LADA/MODY.
  • PT (time) 12.8-14.6 seconds, PTT (time) 25-38 seconds

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 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
  • Abnormal results following screening tests and physical examination that is clinically significant:

Medical history/Physical Exam Exclusion Criteria

  • Fever greater than 38 degrees C at screening or study initiation
  • Uncontrolled severe hypertension (i.e., blood pressure greater than 160/100)
  • Cardiac Abnormalities (e.g. Heart Failure, Arrhythmia, Cardiomyopathy, ischemic tachycardia, S-T segment deviations, etc.,) from history or ECG testing in subjects > 40 years old.
  • Diagnosed Pneumonia
  • Hepatic Failure/Jaundice
  • Clinically significant coagulopathy
  • Renal Failure
  • Acute Cerebrovascular/ Neurological deficit

Screening Laboratory Tests Exclusion Criteria according to protocol

Both
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00829699
HP-00044874, RFAHL04016
Yes
Stephen N. Davis, University of Maryland
University of Maryland
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Stephen N. Davis, MD University of Maryland, Baltimore County
University of Maryland
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP