The Effect of Local Antioxidant Therapy on Racial Differences in Vasoconstriction

NCT03680404 | Completed Phase 1 FDA Drug

• 1 other identifier: 2018-0441
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to examine possible mechanisms of heightened vasoconstriction in Black/African American men and women as possible links to the elevated prevalence of cardiovascular dysfunction and disease. The main targets in this study are sources of oxidative stress.

Conditions

Cardiovascular Diseases; Cardiovascular Risk Factor; Vasoconstriction

Keywords

Racial Differences; Oxidative Stress

Outcome Measures

Primary Outcomes (2)

• Vasoconstrictor Responsiveness to Phenylephrine using Laser Doppler Fluxmetry

  Establish heightened vasoconstriction to phenylephrine stimulation in black men and women with a focus on black women. Following local infusions of phenylephrine, the changes in blood flux will be quantified using laser Doppler fluxmetry. All changes in flux will be normalized and reported as a percentage of baseline flux.

  Through study completion, an average of 1 Year

• Role of Oxidative Stress in Heightened Vasoconstriction using Laser Doppler Fluxmetry

  Determine to what degree superoxide, either generally available or produced through xanthine/NADPH oxidases, contributes to heightened phenylephrine-mediated vasoconstriction. Following local coninfusions of phenylephrine with apocynin, allopurinol, or tempol, the changes in blood flux will be quantified using laser Doppler fluxmetry. All changes in flux will be normalized and reported as a percentage of baseline flux.

  Through study completion, an average of 1 Year

Study Arms (4)

Control (Phenylephrine)

ACTIVE COMPARATOR

Subjects will be administered phenylephrine at varying concentrations (10\^-2 to 10\^-8 M phenylephrine) at a rate of 2 microliters/minute for 10 minutes at each dose to construct a dose-response curve.

Drug: Control (Phenylephrine)

Phenylephrine + Apocynin

EXPERIMENTAL

Subjects will be coinfused with the same phenylephrine concentrations as the control arm and apocynin (10\^-4 M) at the same rate and for the same time as the control arm.

Drug: Phenylephrine + Apocynin

Phenylephrine + Allopurinol

EXPERIMENTAL

Subjects will be coinfused with the same phenylephrine concentrations as the control arm and allopurinol (10\^-5 M) at the same rate and for the same time as the control arm.

Drug: Phenylephrine + Allopurinol

Phenylephrine + Tempol

EXPERIMENTAL

Subjects will be coinfused with the same phenylephrine concentrations as the control arm and Tempol (10\^-5 M) at the same rate and for the same time as the control arm.

Drug: Phenylephrine + Tempol

Interventions

Control (Phenylephrine) DRUG

This intervention is aimed at assessing the vascular responsiveness to phenylephrine, an alpha 1-agonist, in white and black men and women across a series of ascending dose concentrations.

Control (Phenylephrine)

Phenylephrine + Apocynin DRUG

This intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme NADPH oxidase.

Phenylephrine + Apocynin

Phenylephrine + Allopurinol DRUG

This intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme xanthine oxidase.

Phenylephrine + Allopurinol

Phenylephrine + Tempol DRUG

This intervention is meant to assess the impact of superoxide on vasoconstrictor responses by scavenging available superoxide.

Phenylephrine + Tempol

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals (ages 18-35, both genders) will be recruited from the greater Arlington area to participate in the study.
• Must self-report both parents as either African American or Caucasian American.

You may not qualify if:

• Individuals with cardiovascular, neurological, and/or metabolic illnesses will be excluded from participating as well as individuals with a history of various diseases of the microvasculature including Reynaud's disease, cold-induced urticaria, cryoglobulinemia, etc.
• Subjects currently taking any prescription medications and individuals with a body mass index about 30 kg/m2) will be excluded.
• Pregnant subjects and children (i.e. younger than 18) will not be recruited for the study. Eligible females will be scheduled for days 2-7 of their menstrual cycle to account for hormonal effects on blood flow. A regular menstrual cycle is required to identify and schedule the study for the low hormone period, therefore females who lack a regular cycle will be excluded from the study. Females currently taking birth control are eligible, as long as they can be scheduled during a low-hormone "placebo" week. If their hormone do not contain a placebo week than these individuals will not be eligible for data collection. Females who are breast-feeding will also be eligible as there are no systemic or lasting effects of the proposed vasoactive agents.
• Given that smoking can affect the peripheral vasculature, current smokers and individuals who regularly smoked (\>1 pack per two weeks) within the prior 2 years will be excluded

Sponsors & Collaborators

• The University of Texas at Arlington: lead

Study Sites (1)

Science and Engineering Research and Innovation Building

Arlington, Texas, 76019, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Phenylephrine; acetovanillone; Allopurinol; tempol

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Each subject has one control site and three experimental sites concurrently tested within the same study using intradermal microdialysis on the dorsal forearm.

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: September 21, 2018
• Study Start: October 1, 2018
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: November 5, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)