Cardiovascular DiseasesPhase 1NCT03680638
The Effect of Antioxidants on Skin Blood Flow During Local Heating
A Phase 1 study testing Tempol, Apocynin and Allopurinol 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 impaired vasodilaton in obese and 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, Vasodilation
- What is being tested?
- Tempol, Apocynin and Allopurinol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Sep 2016to 9 Oct 2017
- 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
Engineering Research Building
Arlington, Texas, 76019
About this study
The goal of this study is to examine possible mechanisms of impaired vasodilaton in obese and 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
The integrative vascular laboratory has recently observed that the small blood vessels in the skin (the cutaneous microvasculature) in obese (BMI>30kg/m2), but otherwise healthy individuals, require a greater amount of nitric oxide (NO) to achieve the same degree of dilation when compared to age, gender, and race matched lean (BMI<25kg/m2) individuals (34). In addition, it is well documented that African Americans have impaired blood vessel function which likely contributes to the elevated risk for developing a variety of cardiovascular and metabolic diseases including coronary artery disease, metabolic syndrome, hypertension and stroke in this population. The cutaneous circulation is recognized as a surrogate vascular bed for assessment of mechanisms underlying systemic vascular disease (7, 20, 22). This is particularly important as microvascular dysfunction is emerging as a critical step in the atherosclerotic process and a variety of conditions including hypertension, exercise intolerance, and insulin resistance (25). Furthermore, impaired cutaneous microvascular function mirrors impaired responses in other vascular beds (7, 12, 20, 22). A primary advantage to utilizing the cutaneous circulation is that it provides an accessible vascular bed through which processes of endothelial function can be systematically and mechanistically investigated, with virtually no risk, through thermal stimuli and local intra-dermal drug infusions. Mechanisms of impaired NO bioavailability have been assessed in various at-risk and diseased populations including, healthy aging, hypertension, postural tachycardia syndrome, hypercholesteremia, and chronic kidney disease (8, 16, 19, 24, 36, 37). Using approaches and techniques similar to those proposed in this application (see below) the findings have implicated that a number of factors, including elevated oxidative stress, contribute to the reduced bioavailability and/or action of NO (8, 16, 19, 24, 36, 37)
The recent findings suggest an impairment in the action of NO on the microvascular smooth muscle of obese young adults (34) as well as in college-aged otherwise healthy African Americans. Local heating is a common method to test nitric oxide-mediated vasodilation (3, 6, 31). Therefore, the investigators propose to test the following hypotheses:
- Obesity results in impaired blood flow response to local heating and this will also be the case for African Americans.
- Inhibition of superoxide, a common form of oxidative stress, augments the local heating response in obese individuals as well as in African Americans.
- Inhibition of sources of superoxide, NADPH-oxidase and/or Xanthine-oxidase, augments skin blood flow local heating response in obese to that of their lean counterparts. This will also be the case for African Americans relative to their Caucasian American counterparts.
- Being tested
- Control (Lactated Ringer's), Tempol, Apocynin, Allopurinol
- Keywords
- Racial Differences, Oxidative Stress, Obesity, Local Heating
- Medical subject headings
- Cardiovascular Diseases, Aneurysm, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Control (Lactated Ringer's)Other
This intervention is meant to serve as a control by which the experimental sites are compared to, to assess effectiveness.
TempolDrug
This intervention is meant to assess the impact of superoxide on vasodilator responses by scavenging available superoxide.
ApocyninDrug
This intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasodilator responses by inhibiting the enzyme NADPH oxidase.
AllopurinolDrug
This intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasodilator responses by inhibiting the enzyme xanthine oxidase.
| Study group | Role | What they receive |
|---|---|---|
| Control (Lactated Ringer's) | Sham comparator | This site will only be infused with Lactated Ringer's during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. Receives: Other: Control (Lactated Ringer's) |
| Tempol | Experimental | This site will only be infused with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; 10µM) during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. Receives: Drug: Tempol |
| Apocynin | Experimental | This site will only be infused with apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone; 100µM) during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. Receives: Drug: Apocynin |
| Allopurinol | Experimental | This site will only be infused with tempol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one; 10µM) during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. Receives: Drug: Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vasodilator Responses to Local Heating with Antioxidant Supplementation
Assess the impact of oxidative stress on impaired vasodilation to local heating. This will be elicited using intradermal microdialysis infusions of apocynin, allopurinol, or tempol, all of which are vasoactive substances. The changes in skin blood flux will be quantified using laser Doppler fluxmetry. All changes in flux will be normalized and reported as a percentage of maximal 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 start7 Sep 2016
- Primary completion9 Oct 2017
- Study completion9 Oct 2017
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
- 44 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
- NCT03680638
- Sponsor's protocol ID
- 2016-0268
- Status last verified
- Sep 2018
- First submitted
- 17 Sep 2018
- Last updated
- 21 Sep 2018
- 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 21 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Antioxidants on Skin Blood Flow During Local Heating
- ClinicalTrials.gov ID
- NCT03680638
- Acronym / sponsor ID
- 2016-0268
- Keywords
- Racial Differences, Oxidative Stress, Obesity, Local Heating
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- The University of Texas at ArlingtonUniversity, hospital or other
- Study start
- 7 Sep 2016 (actual)
- Primary completion
- 9 Oct 2017 (actual)
- Study completion
- 9 Oct 2017 (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 impaired vasodilaton in obese and 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
The integrative vascular laboratory has recently observed that the small blood vessels in the skin (the cutaneous microvasculature) in obese (BMI>30kg/m2), but otherwise healthy individuals, require a greater amount of nitric oxide (NO) to achieve the same degree of dilation when compared to age, gender, and race matched lean (BMI<25kg/m2) individuals (34). In addition, it is well documented that African Americans have impaired blood vessel function which likely contributes to the elevated risk for developing a variety of cardiovascular and metabolic diseases including coronary artery disease, metabolic syndrome, hypertension and stroke in this population. The cutaneous circulation is recognized as a surrogate vascular bed for assessment of mechanisms underlying systemic vascular disease (7, 20, 22). This is particularly important as microvascular dysfunction is emerging as a critical step in the atherosclerotic process and a variety of conditions including hypertension, exercise intolerance, and insulin resistance (25). Furthermore, impaired cutaneous microvascular function mirrors impaired responses in other vascular beds (7, 12, 20, 22). A primary advantage to utilizing the cutaneous circulation is that it provides an accessible vascular bed through which processes of endothelial function can be systematically and mechanistically investigated, with virtually no risk, through thermal stimuli and local intra-dermal drug infusions. Mechanisms of impaired NO bioavailability have been assessed in various at-risk and diseased populations including, healthy aging, hypertension, postural tachycardia syndrome, hypercholesteremia, and chronic kidney disease (8, 16, 19, 24, 36, 37). Using approaches and techniques similar to those proposed in this application (see below) the findings have implicated that a number of factors, including elevated oxidative stress, contribute to the reduced bioavailability and/or action of NO (8, 16, 19, 24, 36, 37)
The recent findings suggest an impairment in the action of NO on the microvascular smooth muscle of obese young adults (34) as well as in college-aged otherwise healthy African Americans. Local heating is a common method to test nitric oxide-mediated vasodilation (3, 6, 31). Therefore, the investigators propose to test the following hypotheses:
- Obesity results in impaired blood flow response to local heating and this will also be the case for African Americans.
- Inhibition of superoxide, a common form of oxidative stress, augments the local heating response in obese individuals as well as in African Americans.
- Inhibition of sources of superoxide, NADPH-oxidase and/or Xanthine-oxidase, augments skin blood flow local heating response in obese to that of their lean counterparts. This will also be the case for African Americans relative to their Caucasian American counterparts.
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 (Lactated Ringer's) | Sham comparator | Other: Control (Lactated Ringer's)This site will only be infused with Lactated Ringer's during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. |
| Tempol | Experimental | Drug: TempolThis site will only be infused with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; 10µM) during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. |
| Apocynin | Experimental | Drug: ApocyninThis site will only be infused with apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone; 100µM) during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. |
| Allopurinol | Experimental | Drug: AllopurinolThis site will only be infused with tempol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one; 10µM) during the local heating stimulus. After the local heating stimulus, this site will be infused with L-NAME (Nω-nitro-L-arginine methylester; 20mM) to inhibit nitric oxide synthase and with SNP (sodium nitroprusside; 28mM) to elicit vasodilation. This will help establish nitric oxide contribution to vasodilation and establish maximal vasodilation for data normalization, respectively. |
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 (Lactated Ringer's)This intervention is meant to serve as a control by which the experimental sites are compared to, to assess effectiveness. | Other | Control (Lactated Ringer's) |
| TempolThis intervention is meant to assess the impact of superoxide on vasodilator responses by scavenging available superoxide. | Drug | Tempol |
| ApocyninThis intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasodilator responses by inhibiting the enzyme NADPH oxidase. | Drug | Apocynin |
| AllopurinolThis intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasodilator responses by inhibiting the enzyme xanthine oxidase. | Drug | Allopurinol |
Primary outcome
Vasodilator Responses to Local Heating with Antioxidant Supplementation
Time frame: Through study completion, an average of 1 year
Assess the impact of oxidative stress on impaired vasodilation to local heating. This will be elicited using intradermal microdialysis infusions of apocynin, allopurinol, or tempol, all of which are vasoactive substances. The changes in skin blood flux will be quantified using laser Doppler fluxmetry. All changes in flux will be normalized and reported as a percentage of maximal 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 21 Sep 2018.
- Individual participant dataSharing planned: No
Related trials for Cardiovascular Diseases
Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
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 Tempol, Apocynin and Allopurinol 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 21 Sep 2018. 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. Some participants in this study may receive a placebo. 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?
Vasodilator Responses to Local Heating with Antioxidant Supplementation (time frame: Through study completion, an average of 1 year). 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 21 Sep 2018.