Clinical trial NCT00838695: Variability in Adrenergic Response
Official title: Variability in Adrenergic Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vascular Reaction to Medications
Keywords: Hand vein sensitivity
phenylephrine
nitroglycerin
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Research Resources (NCRR)
First posted: 2009-02-06
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: ED50 After Phenylephrine
timeFrame: 70 minutes
Secondary outcomes:
measure: Change in Blood Pressure
timeFrame: baseline to 2 minutes
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Charles M Stein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Paranjape SY, Stein CM, Kurnik D. Blacks have a greater sensitivity to alpha1-adrenoceptor-mediated venoconstriction compared with whites. Hypertension. 2013 Apr;61(4):915-20. doi: 10.1161/HYPERTENSIONAHA.111.00854. Epub 2013 Feb 11.
citation: Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Li C, Paranjape SY, Stein CM, Kurnik D. Genetic variation in the alpha1A-adrenergic receptor and phenylephrine-mediated venoconstriction. Pharmacogenomics J. 2015 Aug;15(4):310-5. doi: 10.1038/tpj.2014.69. Epub 2014 Nov 25.
citation: Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Li C, Levinson RT, Paranjape SY, Stein CM, Kurnik D. Genetic variation in the alpha1B-adrenergic receptor and vascular response. Pharmacogenomics J. 2017 Jul;17(4):366-371. doi: 10.1038/tpj.2016.29. Epub 2016 Apr 19.