NCT03680573

The Effect of Antioxidants on Skin Blood Flow-BH4

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: The University of Texas at Arlington · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

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

Detailed description

African Americans (AA) not only have a higher prevalence of hypertension but the severity of the cardiovascular complications related to this condition are greater in this population relative to other populations. While the underlying causes of this elevated risk are multifactorial, vascular dysfunction (i.e. impaired vasodilation and/or augmented vasoconstriction) is believed to be a key contributing factor. The investigators have recently observed (UTA IRB 2016-0268) that the small blood vessels in the skin (the cutaneous microvasculature) in AA, but otherwise healthy individuals, have an impaired blood flow response in the cutaneous circulation to local heating when compared to age, body mass index (BMI), and gender, matched Caucasians (CA). This blunted response is abolished in AA when the sites are pre-treated with either Allopurinol or Apocynin which block the production of xanthine oxidase and NADPH oxidase, respectively. In addition, Tetrahydrobiopterin (BH4) is critically involved in vascular function. BH4 is a cofactor involved in the conversion of L-Arginine into the potent vasodilator nitric oxide (NO) by the enzyme endothelial nitric oxide synthase (eNOS). Reduced bioavailable BH4 leads to elevated oxidative stress and thus impaired vascular function. In addition to local heating another commonly utilized research approach to assess microcirculatory vascular function is via local infusion of the potent vasodilator methacholine (Mch). Mch is an acetylcholine analog that causes endothelial dependent vasodilation primarily through stimulation of NO production. Much like the local heating data mentioned above, our laboratory (data collected while at UT Austin) has demonstrated a blunted response to Mch in AA relative to CA. However, the role of xanthine oxidase, NADPH oxidase, and BH4 in this blunted response remains unknown.

Conditions

• Cardiovascular Diseases
• Cardiovascular Risk Factor
• Vasoconstriction

Interventions

Type	Name	Description
DRUG	Control: Lacated Ringers	This site will serve as the control site
DRUG	Apocynin	This site will be used to inhibit NADPH oxidase and subsequent production of superoxide.
DRUG	Allopurinol	This site will be use to inhibit xanthine oxidase and subsequent production of superoxide.
DRUG	BH4	This site will be use to locally supplement BH4.
DRUG	NG Nitro L Arginine Methyl Ester	L-Name is a NOS inhibitor that is administered to each site to allow for the quantification of NO contribution to vasodilation. The infusion rate will be 2 µl/min
DRUG	Sodium Nitroprusside	SNP will be perfused through each site to induce maximal vasodilation. The infusion rate will be 2 µl/min
DRUG	Acetyl-ß-methylcholine chloride	Mch is an acetylcholine analog that causes endothelial dependent vasodilation primarily through stimulation of NO production.

Timeline

• Start date: 2018-01-08
• Primary completion: 2018-05-05
• Completion: 2018-05-05
• First posted: 2018-09-21
• Last updated: 2018-09-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study