The Effect of Antioxidants on Skin Blood Flow During Local Heating

NCT03680638 | Completed Phase 1 FDA Drug

• 1 other identifier: 2016-0268
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cardiovascular Diseases; Cardiovascular Risk Factor; Vasodilation

Keywords

Racial Differences; Oxidative Stress; Obesity; Local Heating

Outcome Measures

Primary Outcomes (1)

• 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.

  Through study completion, an average of 1 year

Study Arms (4)

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.

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.

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.

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.

Drug: Allopurinol

Interventions

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.

Control (Lactated Ringer's)

Tempol DRUG

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

Tempol

Apocynin DRUG

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

Apocynin

Allopurinol DRUG

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

Allopurinol

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)

Engineering Research Building

Arlington, Texas, 76019, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Aneurysm; Obesity

Interventions

Ringer's Lactate; tempol; acetovanillone; Allopurinol

Condition Hierarchy (Ancestors)

Vascular Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; 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: September 7, 2016
• Primary Completion: October 9, 2017
• Study Completion: October 9, 2017
• Last Updated: September 21, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)