Cardiovascular DiseasesPhase 1NCT03680404
The Effect of Local Antioxidant Therapy on Racial Differences in Vasoconstriction
A Phase 1 study testing Phenylephrine + Apocynin, Phenylephrine + Allopurinol and Phenylephrine + Tempol in people with Cardiovascular Diseases and Cardiovascular Risk Factor, run by The University of Texas at Arlington at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Cardiovascular Risk Factor, Vasoconstriction
- What is being tested?
- Phenylephrine + Apocynin, Phenylephrine + Allopurinol and Phenylephrine + Tempol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2018to 1 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Science and Engineering Research and Innovation Building
Arlington, Texas, 76019
About this study
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.
Read the 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.
- Being tested
- Control (Phenylephrine), Phenylephrine + Apocynin, Phenylephrine + Allopurinol, Phenylephrine + Tempol
- Keywords
- Racial Differences, Oxidative Stress
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Phenylephrine + ApocyninDrug
This intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme NADPH oxidase.
Phenylephrine + AllopurinolDrug
This intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme xanthine oxidase.
Phenylephrine + TempolDrug
This intervention is meant to assess the impact of superoxide on vasoconstrictor responses by scavenging available superoxide.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Phenylephrine + Tempol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Through study completion, an average of 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2018
- Study start1 Oct 2018
- Primary completion1 Feb 2020
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each subject has one control site and three experimental sites concurrently tested within the same study using intradermal microdialysis on the dorsal forearm.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Texas at Arlington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthew Brothers, The University of Texas at Arlington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03680404
- Sponsor's protocol ID
- 2018-0441
- Status last verified
- Nov 2020
- First submitted
- 17 Sep 2018
- Last updated
- 5 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Local Antioxidant Therapy on Racial Differences in Vasoconstriction
- ClinicalTrials.gov ID
- NCT03680404
- Acronym / sponsor ID
- 2018-0441
- Keywords
- Racial Differences, Oxidative Stress
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- The University of Texas at ArlingtonUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 21 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Each subject has one control site and three experimental sites concurrently tested within the same study using intradermal microdialysis on the dorsal forearm.
| Arm | Type | Receives |
|---|---|---|
| Control (Phenylephrine) | Active comparator | Drug: 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. |
| Phenylephrine + Apocynin | Experimental | Drug: Phenylephrine + ApocyninSubjects 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. |
| Phenylephrine + Allopurinol | Experimental | Drug: Phenylephrine + AllopurinolSubjects 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. |
| Phenylephrine + Tempol | Experimental | Drug: Phenylephrine + TempolSubjects 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Control (Phenylephrine) |
| Phenylephrine + ApocyninThis intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme NADPH oxidase. | Drug | Phenylephrine + Apocynin |
| Phenylephrine + AllopurinolThis intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasoconstrictor responses by inhibiting the enzyme xanthine oxidase. | Drug | Phenylephrine + Allopurinol |
| Phenylephrine + TempolThis intervention is meant to assess the impact of superoxide on vasoconstrictor responses by scavenging available superoxide. | Drug | Phenylephrine + Tempol |
Primary outcome
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Phenylephrine + Apocynin, Phenylephrine + Allopurinol and Phenylephrine + Tempol in people with Cardiovascular Diseases and Cardiovascular Risk Factor, run by The University of Texas at Arlington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vasoconstrictor Responsiveness to Phenylephrine using Laser Doppler Fluxmetry (time frame: Through study completion, an average of 1 Year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2020; AzTrials last refreshed its copy on 6 Nov 2026.