Hypoglycemia Associated Autonomic Dysfunction Dose Response of Epinephrine
Overview
- Phase
- Early Phase 1
- Status
- Completed
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Flow mediated dilation (FMD) of the brachial artery
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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)
Arms & Interventions
Saline infusion
Hyperinsulinemic euglycemic glucose clamp with saline infusion
Intervention: Saline infusion (Other)
Epinephrine infusion-0.015ug/kg/min
Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.015 ug/kg/min
Intervention: Epinephrine (Drug)
Epinephrine infusion-0.03 ug/kg/min
Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.03 ug/kg/min
Intervention: Epinephrine (Drug)
Epinephrine infusion-0.06 ug/kg/min
Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.06 ug/kg/min
Intervention: Epinephrine (Drug)
Outcomes
Primary Outcomes
Flow mediated dilation (FMD) of the brachial artery
Time Frame: From baseline (pre glucose clamp) to end of experiment (time 240 minutes- 2 hours post intervention (glucose clamp))
Measurements of FMD will be taken at baseline (pre intervention) and end of glucose clamp (post intervention) and the maximal % change determined
Secondary Outcomes
No secondary outcomes reported
Investigators
Stephen N. Davis, MBBS
Chairman of Medicine
University of Maryland, Baltimore