Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03679780 |
| Other study ID # |
2018-0648 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2018 |
| Est. completion date |
July 26, 2023 |
Study information
| Verified date |
June 2024 |
| Source |
The University of Texas at Arlington |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of the study is to examine the possible mechanisms of impaired cutaneous
microvascular function through local heating along with administration of vasoconstrictors.
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. Across a series of studies conducted in our laboratory we have consistently
observed impaired microvascular function in the small blood vessels in the skin (the
cutaneous microvasculature) in AA relative to age, sex, and body mass index Caucasian
Americans (CA). From a research design perspective this offers the opportunity to conduct
minimally invasive studies while investigating research questions in a systematic and
mechanistic manner. Furthermore, the cutaneous circulation is recognized as surrogate
vascular bed for assessment of mechanisms underlying systemic vascular disease and
microvascular dysfunction is emerging as a critical step in the artherosclerotic process and
a variety of conditions including hypertension, exercise intolerance, and insulin resistance.
And, impaired cutaneous microvascular function mirrors impaired responses in other vascular
beds. A primary advantage to utilizing the cutaneous circulation is that it provides an
accessible vascular bed through which processes of endothelial function can be investigated,
with virtually no risk, through thermal stimuli and local intra-dermal drug infusions.
In terms of the AA population our group and others have documented that impaired vascular
function and elevated disease risk is related, in part, to reductions in bioavailability of
the potent vasodilator Nitric oxide (NO). While, this has become fairly common knowledge what
remains less well defined is the mechanisms of this reduced NO bioavailability. We have
recently identified a role for oxidative stress in this process. However, oxidative stress is
a complex process and likely does not explain all of the observed impairment. 2 other
possibilities that are attractive candidate targets for mechanistic studies are the
endothelin pathway as well as bioavailability of L-Arginine. Endothelin is a hormone that has
been implicated in many populations with elevated CVD risk as it is a potent vasoconstrictor
which also can reduce NO bioavailability. Interestingly, there are reports of elevated
endothelin circulating concentration and/or increased sensitivity and thus vasoconstriction
to endothelin in AA. L-Arginine is a naturally occurring amino acid that is required for the
full endogenous production of NO. In other words reduced L-Arginine bioavailability is
present in many disease conditions and contributes to vascular dysfunction. In regards to AA
it is reported that they have reduced natural production of L-arginine and also respond more
positively to intra coronary infusion of L-arginine relative to other populations. However,
to our knowledge the role of the endothelin system as well as L-arginine in microvascular
dysfunction in AA has never been investigated.
