- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03680638
The Effect of Antioxidants on Skin Blood Flow During Local Heating
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Texas
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Arlington, Texas, United States, 76019
- Engineering Research Building
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Sham Comparator: 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.
|
This intervention is meant to serve as a control by which the experimental sites are compared to, to assess effectiveness.
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Experimental: Tempol
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.
|
This intervention is meant to assess the impact of superoxide on vasodilator responses by scavenging available superoxide.
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Experimental: Apocynin
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.
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This intervention is meant to assess the impact of NADPH oxidase-derived superoxide on vasodilator responses by inhibiting the enzyme NADPH oxidase.
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Experimental: Allopurinol
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.
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This intervention is meant to assess the impact of xanthine oxidase-derived superoxide on vasodilator responses by inhibiting the enzyme xanthine oxidase.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vasodilator Responses to Local Heating with Antioxidant Supplementation
Time Frame: Through study completion, an average of 1 year
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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.
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Through study completion, an average of 1 year
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites
- Neuroprotective Agents
- Protective Agents
- Protein Synthesis Inhibitors
- Antioxidants
- Free Radical Scavengers
- Gout Suppressants
- Radiation-Protective Agents
- Tempol
- Allopurinol
Other Study ID Numbers
- 2016-0268
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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