Variability in Adrenergic Response

NCT00838695 | Completed Results

• 3 other identifiers: 71148P01HL0566931UL1RR024975
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

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.

Conditions

Vascular Reaction to Medications

Keywords

Hand vein sensitivity; phenylephrine; nitroglycerin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in Blood Pressure

  baseline to 2 minutes

Study Arms (2)

African Americans

EXPERIMENTAL

Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing

Drug: Phenylephrine

Caucasians

EXPERIMENTAL

Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing

Drug: Phenylephrine

Interventions

Phenylephrine DRUG

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)

Also known as: generic medications used,not applicable

African Americans; Caucasians

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• 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.

  PMID: 23399717 RESULT

• 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.

  PMID: 25421140 RESULT

• 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.

  PMID: 27089938 RESULT

MeSH Terms

Interventions

Phenylephrine

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Limitations and Caveats

Findings derived from dorsal hand veins and cannot automatically be extrapolated to other vascular beds. Women were not studied at predefined periods of menstrual cycle or account for use of hormonal contraceptives. Some genotype groups were small.

Results Point of Contact

• Title: Dr. C. Michael Stein
• Organization: VAnderbilt University Medical Center

mike.stein@vumc.org

615-936-3420

Study Officials

• Charles M Stein, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dan May Professor of Medicine, Professor of Pharmacology, Assistant Director of the Division of Clinical Pharmacology

Study Record Dates

• First Submitted: February 4, 2009
• First Posted: February 6, 2009
• Study Start: January 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2011
• Last Updated: October 26, 2018
• Results First Posted: October 26, 2018

Record last verified: 2018-10

Locations

US (1)