Variability in Adrenergic Response

Study Overview
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Brief Summary
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The goal of this project is to determine the genetic factors contributing to interindividual differences in response to physiological and pharmacological vasoconstrictors and vasodilators.

Detailed Description
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The dorsal hand vein model is a relatively non-invasive and robust experimental model to examine the local in vivo effect of vasoactive drugs without elucidating systemic counterregulatory reflexes. Infusion of incremental low doses of phenylephrine into a dorsal hand vein results in increasing local venoconstriction, without systemic effects. Similarly, infusion of incremental low doses of nitroglycerin into a preconstricted dorsal hand vein results in increasing local venodilation, without systemic effects. Systemic vascular responses can be measured by the cold pressor test (CPT),that leads to increase in blood pressure and heart rate , or mental stress that is also known to stimulate cardiovascular responses. Individuals vary in their local and systemic vascular responses but the genetic determinants of these are not clear.

Official Title
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Variability in Adrenergic Response

Conditions
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Vascular Reaction to Medications

Intervention / Treatment
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* Drug: Phenylephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 40 years, inclusive. Subject must be willing to give written informed consent and be able to adhere to diet and study schedules. Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with the study evaluations. Subjects must have a normal or clinically acceptable physical examination and ECG. Clinical laboratory tests (CBC, blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator. Exclusion Criteria: Any subject who has taken any prescription or over-the-counter drugs, other than oral contraception if female, within two weeks prior to study drug administration. Subjects who are presently, or were formerly, narcotic addicts or alcoholics. Subjects who have a clinically significant allergy/intolerance to phenylephrine. Females with a positive serum/urine pregnancy test at screening. Females who are nursing. Subject using sildenafil or other phosphodiesterase inhibitors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: African Americans<br>Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing | Drug: Phenylephrine<br>* Intravenous phenylephrine at low doses (approximately 10 doses ranging from 0-5000 ng/min) Intravenous nitroglycerin at low doses (approximately 10 doses ranging from 0.05-100 ng/min)<br>* Other names: generic medications used,not applicable;|
| Experimental: Caucasians<br>Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing | Drug: Phenylephrine<br>* Intravenous phenylephrine at low doses (approximately 10 doses ranging from 0-5000 ng/min) Intravenous nitroglycerin at low doses (approximately 10 doses ranging from 0.05-100 ng/min)<br>* Other names: generic medications used,not applicable;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ED50 After Phenylephrine | ED50 is a measurement of vein constriction and indicates 50% of maximal constriction after being given medication phenylephrine, representing sensitivity to the drug. Phenylephrine was infused at increasing dose rates, ranging from 12-9600 ng/min. The infusion at each dose rate lasted 7 minutes, with the vein diameter measured during the last 2 minutes of the infusion. The number represents the ng/ml of phenylephrine needed to reach 50% of maximal vein constriction. ED50 values were not normally distributed and were log-transformed for analysis and expressed as geometric means. | 70 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Pressure | change in systolic and diastolic blood pressure, comparing before and after cold pressor test. A subset of 57 participants (of the 106) who were in the primary outcome measure also participated in the cold pressor test. | baseline to 2 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hand vein sensitivity, phenylephrine, nitroglycerin