Dose Response of Epinephrine

Study Overview
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Brief Summary
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Epinephrine is the principal physiologic defense against hypoglycemia in type 1 and longer duration type 2 DM. Despite this, it is unknown how epinephrine regulates in-vivo endothelial function and atherothrombotic balance in humans. The specific aim of our study will be to determine the dose response effects of the key ANS counterregulatory hormone epinephrine on endothelial function, fibrinolytic balance and pro-atherogenic inflammatory mechanisms in healthy humans.

Official Title
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Hypoglycemia Associated Autonomic Dysfunction Dose Response of Epinephrine

Conditions
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Diabetes Complications

Intervention / Treatment
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* Drug: Epinephrine
* Other: Saline infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy controls age 18-55 yr. Body mass index >21 kg · m-2 Exclusion Criteria: Pregnant or breastfeeding women Subjects unwilling or unable to comply with approved contraception measures Subjects unable to give voluntary informed consent Subjects on anticoagulant drugs, anemic or with known bleeding diatheses Subjects with a history of severe, uncontrolled hypertension, heart disease, cerebrovascular incidents Current tobacco use Subjects with any known allergies to any of the study medications being used Physical Exam Exclusion Criteria Uncontrolled severe hypertension (i.e., blood pressure greater than 160/100) Clinically significant cardiac abnormalities (e.g. heart failure, arrhythmia) Pneumonia treatment or hospitalization within 2 weeks prior to enrollment (study visit) Hepatic failure / jaundice Renal failure Cerebrovascular accident occurrence or hospitalization within 4 weeks prior to enrollment Fever greater than 38.0 degrees C Screening Laboratory Tests Exclusion Criteria Hematocrit lower than 32 % White blood cell (WBC) count lower than 3 thou/ul or greater than 14 thou/ul Liver function tests: serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) greater than twice upper limit of normal range Alkaline phosphatase greater than 150U/L Total bilirubin (TBil) greater than 2 mg/dl Estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 Positive human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C Any abnormal cardiac response during multi-stage exercise test (if over 40 years of age)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline infusion<br>Hyperinsulinemic euglycemic glucose clamp with saline infusion | Other: Saline infusion<br>* Placebo<br>* Other names: Placebo;|
| Experimental: Epinephrine infusion-0.015ug/kg/min<br>Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.015 ug/kg/min | Drug: Epinephrine<br>* Dose response of epinephrine infusion<br>* Other names: Adrenaline;|
| Experimental: Epinephrine infusion-0.03 ug/kg/min<br>Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.03 ug/kg/min | Drug: Epinephrine<br>* Dose response of epinephrine infusion<br>* Other names: Adrenaline;|
| Experimental: Epinephrine infusion-0.06 ug/kg/min<br>Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.06 ug/kg/min | Drug: Epinephrine<br>* Dose response of epinephrine infusion<br>* Other names: Adrenaline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow mediated dilation (FMD) of the brachial artery | Measurements of FMD will be taken at baseline (pre intervention) and end of glucose clamp (post intervention) and the maximal % change determined | From baseline (pre glucose clamp) to end of experiment (time 240 minutes- 2 hours post intervention (glucose clamp)) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epinephrine, counterregulation, dose responses