Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus

Type 2 Diabetes Clinical Trial

Official title:

Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus, Question 3

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00829699
• Other study ID #: HP-00044874
• Secondary ID: RFAHL04016
• Status: Completed
• Phase: Early Phase 1
• Start date: July 2009
• Est. completion date: April 2014

Study information

• Verified date: September 2019
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: April 2014
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Thrombosis
• Type 2 Diabetes

Intervention

Procedure:
• euinsulinemic euglycemic glucose clamp
euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours
• euinsulinemic hyperglycemic glucose clamp
euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
• Hyperinsulinemic euglycemic glucose clamp
Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
• Hyperinsulinemic hyperglycemic glucose clamp
Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours

Locations

Country	Name	City	State
United States	Univerisity of Maryland, Baltimore	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in flow mediated dilation of brachial artery		4 hours
Secondary	Change in Lipid measures		4hours