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Metabolic Causes of Thrombosis in Type 2 Diabetes - Question 4

Primary Purpose

Type 2 Diabetes

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Hyperinsulinemic Hypoglycemic Clamp

About this trial

This is an interventional prevention trial for Type 2 Diabetes focused on measuring Type 2 Diabetes, Endothelial Function, Fibrinolytic Balance, Hypoglycemia

Eligibility Criteria

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

Inclusion Criteria

14 (7 female/ 7 male) Type 2 diabetic patients age 18-60 yrs
14 (7 female/ 7 male) Non-diabetic controls age and weight matched
Body mass index >20 kg/m2
Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities
Female volunteers of childbearing potential: negative HCG pregnancy test
Volunteers over 40 years old: normal baseline cardiac stress test
For those with type 2 diabetes: HBA1C >5.5%
For those with type 2 diabetes: diabetes < 20 years
For those with type 2 diabetes: C-peptide >0.2 nmol (1.1-4.4 ng/ml). If c-peptide is abnormal or there is a clinical suspicion of type 1 diabetes, MODY, or LADA, Anti-Islet cell (negative) and Glutamic Acid Decarboxylase (GAD) antibody negative (0.0-1.5 U/ml) will be performed

Exclusion Criteria

Uncontrolled hypertension
History of cerebrovascular incidents
Pregnancy
Subjects unable to give voluntary informed consent
Subjects with a recent medical illness
Subjects on anticoagulant drugs, anemic, or with known bleeding diseases
Tobacco Use

Physical Exam Exclusion Criteria

Blood Pressure greater than 150/95
Clinically significant Cardiac Abnormalities (e.g. Heart Failure, Arrhythmias, ischemic tachycardia, S-T segment deviations, ect.) from history or from cardiac stress testing
Pneumonia
Hepatic Failure/Jaundice
Renal Failure
Acute Cerebrovascular/ Neurological deficit
Fever greater than 38.0 C

Screening blood tests exclusions according to protocol

Sites / Locations

University of Maryland, Baltimore

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Control study then antecedent hypoglycemia study group

Antecedent Hypoglycemic clamp study

Arm Description

Day 1 euglycemia, day 2 hypoglycemia Hyperinsulinemic Hypoglycemic Clamp: hyperinsulinemic glucose clamp separated by 8 weeks then participants proceeded to antecedent hypoglycemia study Day 1 hypoglycemia, Day 2 hypoglycemia

Day 1 hypoglycemia, day 2 hypoglycemia Hyperinsulinemic Hypoglycemic Clamp: hyperinsulinemic glucose clamp separated by 8 weeks then participants proceeded to control study Day 1 euglycemia, Day 2 hypoglycemia

Outcomes

Primary Outcome Measures

Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2

A measure of the baseline arterial dilation on day 2 is compared to the post intervention measure of dilation of the brachial artery on Day 2.

Secondary Outcome Measures

Full Information

NCT ID

NCT00574340

First Posted

December 13, 2007

Last Updated

September 10, 2019

Sponsor

University of Maryland, Baltimore

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT00574340

Brief Title

Metabolic Causes of Thrombosis in Type 2 Diabetes - Question 4

Official Title

SCCOR in Hemostatic and Thrombotic Diseases Project 5 - Metabolic Causes of Thrombosis in Type 2 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

May 2007 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

April 2011 (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

Hypoglycemia (low blood glucose level) occurs frequently in intensively treated patients with diabetes. Although hypoglycemia was thought to occur almost exclusively in T1DM, with the advent of improved metabolic control in T2DM, the incidence of hypoglycemia is rising in these patients. Therefore in this application, we will test the novel hypothesis that prior hypoglycemia will result in (cardiovascular complications) during subsequent hypoglycemia.

Detailed Description

This study will test the hypothesis that 1) hypoglycemia causes a prothrombotic state and defective endothelial function and 2) episodes of repeated hypoglycemia will result in greater impairments of endothelial function and an increased prothrombotic tendency. Preliminary data in healthy men demonstrates that hypoglycemia can dramatically increase PAI-1 levels and the PAI-1 to tPA ratio, thereby creating a prothrombotic state. Whether this also occurs in type 2 DM patients is unknown. Furthermore, the effects of hypoglycemia on endothelial function in T2DM are also unknown.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes

Keywords

Type 2 Diabetes, Endothelial Function, Fibrinolytic Balance, Hypoglycemia

7. Study Design

Primary Purpose

Prevention

Study Phase

Early Phase 1

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control study then antecedent hypoglycemia study group

Arm Type

Active Comparator

Arm Description

Arm Title

Antecedent Hypoglycemic clamp study

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

Hyperinsulinemic Hypoglycemic Clamp

Intervention Description

all participants received (2) hyperinsulinemic glucose clamp studies separated by 8 weeks

Primary Outcome Measure Information:

Title

Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2

Description

A measure of the baseline arterial dilation on day 2 is compared to the post intervention measure of dilation of the brachial artery on Day 2.

Time Frame

baseline on day 2 and ~6 hours later at end of glucose clamp period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria 14 (7 female/ 7 male) Type 2 diabetic patients age 18-60 yrs 14 (7 female/ 7 male) Non-diabetic controls age and weight matched Body mass index >20 kg/m2 Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities Female volunteers of childbearing potential: negative HCG pregnancy test Volunteers over 40 years old: normal baseline cardiac stress test For those with type 2 diabetes: HBA1C >5.5% For those with type 2 diabetes: diabetes < 20 years For those with type 2 diabetes: C-peptide >0.2 nmol (1.1-4.4 ng/ml). If c-peptide is abnormal or there is a clinical suspicion of type 1 diabetes, MODY, or LADA, Anti-Islet cell (negative) and Glutamic Acid Decarboxylase (GAD) antibody negative (0.0-1.5 U/ml) will be performed Exclusion Criteria Uncontrolled hypertension History of cerebrovascular incidents Pregnancy Subjects unable to give voluntary informed consent Subjects with a recent medical illness Subjects on anticoagulant drugs, anemic, or with known bleeding diseases Tobacco Use Physical Exam Exclusion Criteria Blood Pressure greater than 150/95 Clinically significant Cardiac Abnormalities (e.g. Heart Failure, Arrhythmias, ischemic tachycardia, S-T segment deviations, ect.) from history or from cardiac stress testing Pneumonia Hepatic Failure/Jaundice Renal Failure Acute Cerebrovascular/ Neurological deficit Fever greater than 38.0 C Screening blood tests exclusions 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

University of Maryland, Baltimore

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

25695946

Citation

Joy NG, Tate DB, Younk LM, Davis SN. Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans. Diabetes. 2015 Jul;64(7):2571-80. doi: 10.2337/db14-1729. Epub 2015 Feb 18.

Results Reference

result

PubMed Identifier

20587723

Citation

Gogitidze Joy N, Hedrington MS, Briscoe VJ, Tate DB, Ertl AC, Davis SN. Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals. Diabetes Care. 2010 Jul;33(7):1529-35. doi: 10.2337/dc09-0354. Erratum In: Diabetes Care. 2010 Sep;33(9):2129.

Results Reference

derived

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Metabolic Causes of Thrombosis in Type 2 Diabetes - Question 4

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