Clinical trial NCT00829699: Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus
Official title: Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus, Question 3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Type 2 Diabetes
Keywords: endothelial function
fibrinolytic balance
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-01-27
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Percent change in flow mediated dilation of brachial artery
timeFrame: 4 hours
Secondary outcomes:
measure: Change in Lipid measures
timeFrame: 4hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Univerisity of Maryland, Baltimore
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Stephen N. Davis, MD
role: PRINCIPAL_INVESTIGATOR
References: