Metabolic Causes of Thrombosis in Type 2 Diabetes - Question 4

September 10, 2019 updated by: Stephen N. Davis, MBBS, University of Maryland, Baltimore

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, Baltimore

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Control study then antecedent hypoglycemia study group
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
Other: Hyperinsulinemic Hypoglycemic Clamp
all participants received (2) hyperinsulinemic glucose clamp studies separated by 8 weeks
ACTIVE_COMPARATOR: Antecedent Hypoglycemic clamp study
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
Other: Hyperinsulinemic Hypoglycemic Clamp
all participants received (2) hyperinsulinemic glucose clamp studies separated by 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2
Time Frame: baseline on day 2 and ~6 hours later at end of glucose clamp period
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.
baseline on day 2 and ~6 hours later at end of glucose clamp period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (ACTUAL)

April 1, 2011

Study Completion (ACTUAL)

April 1, 2011

Study Registration Dates

First Submitted

December 13, 2007

First Submitted That Met QC Criteria

December 13, 2007

First Posted (ESTIMATE)

December 17, 2007

Study Record Updates

Last Update Posted (ACTUAL)

September 12, 2019

Last Update Submitted That Met QC Criteria

September 10, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00044875-SCCOR-Q4
  • RFAHL04016

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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