The Effect of Local Antioxidant Therapy on Racial Differences in Vasoconstriction

November 4, 2020 updated by: Matthew Brothers, The University of Texas at Arlington
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cardiovascular disease (CVD) afflicts nearly one-third of the adult population with all races and ethnicities represented in CVD prevalence. Unfortunately, a disparity exists such that the black population (BL) is disproportionately affected compared to other groups, including the white population (WH). While the underlying cause of this disparity is multifactorial, vascular dysfunction (i.e., impaired vasodilation and/or augmented vasoconstriction) is a key contributor. As has been previously observed, BL exhibit a heightened vasoconstrictor response to both pharmacological (e.g., alpha-adrenergic receptor agonists) and environmental (e.g., cold pressor test) stimuli compared to their WH counterparts. Additionally, reactive oxygen species (ROS) and the subsequent reduction in nitric oxide (NO) bioavailability may partially mediate this response.

Interestingly, the small blood vessels in the skin (cutaneous microvasculature) in BL, but otherwise healthy individuals, produce an impaired blood flow response to local heating when compared to age-, body mass index (BMI)-, and gender-matched WH. However, pre-treatment of the cutaneous microvasculature with either allopurinol or apocynin (xanthine oxidase inhibitor and NADPH oxidase inhibitor, respectively) abolishes this skin blood flow difference. These drugs inhibit possible sources of ROS, which, as mentioned, may be mediating the heightened vasoconstrictor response in BL. Accordingly, apocynin administration in previous research using an animal model ameliorates alpha-adrenergic receptor-mediated vasoconstriction, possibly due to a reduction in ROS. The role of xanthine/NADPH oxidase and the production of ROS on alpha-adrenergic receptor-mediated vasoconstriction in humans remains unknown.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Arlington, Texas, United States, 76019
        • Science and Engineering Research and Innovation Building

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Individuals who have donated more than 550 ml of blood within the past 8 weeks will not have blood drawn from them in this protocol. However, if they remain interested in the study, and otherwise meet the inclusion criteria, than we may still opt to proceed with data collection.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control (Phenylephrine)
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)
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.
Experimental: Phenylephrine + Apocynin
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
This intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme NADPH oxidase.
Experimental: Phenylephrine + Allopurinol
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
This intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme xanthine oxidase.
Experimental: Phenylephrine + Tempol
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
This intervention is meant to assess the impact of superoxide on vasoconstrictor responses by scavenging available superoxide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vasoconstrictor Responsiveness to Phenylephrine using Laser Doppler Fluxmetry
Time Frame: Through study completion, an average of 1 Year
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
Time Frame: Through study completion, an average of 1 Year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas at Arlington

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2018

Primary Completion (Actual)

February 1, 2020

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

September 17, 2018

First Submitted That Met QC Criteria

September 19, 2018

First Posted (Actual)

September 21, 2018

Study Record Updates

Last Update Posted (Actual)

November 5, 2020

Last Update Submitted That Met QC Criteria

November 4, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-0441

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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