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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus, Question 3

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Percent change in flow mediated dilation of brachial artery [ Time Frame: 4 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Lipid measures [ Time Frame: 4hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: July 2009
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Euinsulinemic (low insulin infusion) Euglycemic (normal blood glucose levels) glucose clamp with lipid (fat) infusion
Procedure: euinsulinemic euglycemic glucose clamp
euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours
Other Name: Intralipid
Experimental: 2
Euinsulinemic Hyperglycemic (high glucose levels) glucose clamp with lipid infusion
Procedure: euinsulinemic hyperglycemic glucose clamp
euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
Other Name: Intralipid
Experimental: 3
Hyperinsulinemic (High dose insulin) 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
Other Name: Intralipid
Experimental: 4
Hyperinsulinemic hyperglycemic (high glucose level) glucose clamp with lipid infusion
Procedure: Hyperinsulinemic hyperglycemic glucose clamp
Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
Other Name: Intralipid

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 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.

  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 - 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

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

Locations
United States, Maryland
Univerisity of Maryland, Baltimore
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Stephen N. Davis, MD University of Maryland, Baltimore County
  More Information

No publications provided

Responsible Party: Stephen N. Davis, Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT00829699     History of Changes
Other Study ID Numbers: HP-00044874, RFAHL04016
Study First Received: January 23, 2009
Last Updated: May 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
endothelial function
fibrinolytic balance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Thrombosis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 15, 2014