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Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus

Primary Purpose

Type 2 Diabetes

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
euinsulinemic euglycemic glucose clamp
euinsulinemic hyperglycemic glucose clamp
Hyperinsulinemic euglycemic glucose clamp
Hyperinsulinemic hyperglycemic glucose clamp
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Type 2 Diabetes focused on measuring endothelial function, fibrinolytic balance

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Univerisity of Maryland, Baltimore

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

Arm Description

Euinsulinemic (low insulin infusion) Euglycemic (normal blood glucose levels) glucose clamp with lipid (fat) infusion

Euinsulinemic Hyperglycemic (high glucose levels) glucose clamp with lipid infusion

Hyperinsulinemic (High dose insulin) euglycemic glucose clamp with lipid infusion

Hyperinsulinemic hyperglycemic (high glucose level) glucose clamp with lipid infusion

Outcomes

Primary Outcome Measures

Percent change in flow mediated dilation of brachial artery

Secondary Outcome Measures

Change in Lipid measures

Full Information

First Posted
January 23, 2009
Last Updated
September 10, 2019
Sponsor
University of Maryland, Baltimore
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00829699
Brief Title
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

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
endothelial function, fibrinolytic balance

7. Study Design

Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Factorial Assignment
Masking
Participant
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Euinsulinemic (low insulin infusion) Euglycemic (normal blood glucose levels) glucose clamp with lipid (fat) infusion
Arm Title
2
Arm Type
Experimental
Arm Description
Euinsulinemic Hyperglycemic (high glucose levels) glucose clamp with lipid infusion
Arm Title
3
Arm Type
Experimental
Arm Description
Hyperinsulinemic (High dose insulin) euglycemic glucose clamp with lipid infusion
Arm Title
4
Arm Type
Experimental
Arm Description
Hyperinsulinemic hyperglycemic (high glucose level) glucose clamp with lipid infusion
Intervention Type
Procedure
Intervention Name(s)
euinsulinemic euglycemic glucose clamp
Other Intervention Name(s)
Intralipid
Intervention Description
euinsulinemic euglycemic glucose clamp with lipid infusion 48 ml/hr for 4 hours
Intervention Type
Procedure
Intervention Name(s)
euinsulinemic hyperglycemic glucose clamp
Other Intervention Name(s)
Intralipid
Intervention Description
euinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
Intervention Type
Procedure
Intervention Name(s)
Hyperinsulinemic euglycemic glucose clamp
Other Intervention Name(s)
Intralipid
Intervention Description
Hyperinsulinemic euglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
Intervention Type
Procedure
Intervention Name(s)
Hyperinsulinemic hyperglycemic glucose clamp
Other Intervention Name(s)
Intralipid
Intervention Description
Hyperinsulinemic hyperglycemic glucose clamp with lipid infusion at 48 ml/hr for 4 hours
Primary Outcome Measure Information:
Title
Percent change in flow mediated dilation of brachial artery
Time Frame
4 hours
Secondary Outcome Measure Information:
Title
Change in Lipid measures
Time Frame
4hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen N. Davis, MD
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Univerisity of Maryland, Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

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Metabolic Causes of Thrombosis in Type 2 Diabetes Mellitus

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