Comparing Approaches to Assess Nitric Oxide-dependent Cutaneous Vasodilation (CAP NOVA)

The increase in skin blood flow in response to rapid local heating of the skin (i.e., cutaneous vasodilation) is commonly used to assess nitric oxide (NO)-dependent dilation and overall microvascular function. Historically, rapid local heating to 42°C was considered the standard approach for these assessments. More recently, many investigators have adopted rapid local to 39°C instead, based on its larger dependency on NO and therefore improved ability to quantify NO-dependent dilation without the use of pharmacological techniques. However, to date, only one direct methodological comparison between these protocols has been performed.

In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) they examine the blood vessels in a nickel-sized area of the skin in young adults ages 18 - 30 years old. Local heating of the skin at the microdialysis sites is used to explore differences in mechanisms governing microvascular control. As a compliment to these measurements, the investigators also have participants fill out a variety of surveys to assess things such as sleep quality, physical activity, daily stressors, etc.

Study Overview

• Status: Recruiting
• Conditions: Endothelial Function
• Intervention / Treatment: Drug: Acetylcholine

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Anna Stanhewicz, PhD; Phone Number: 3194671732; Email: anna-stanhewicz@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Anna Stanhewicz, PhD; Phone Number: 319-467-1732; Email: anna-stanhewicz@uiowa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• men and women
• 18-30 years of age

Exclusion Criteria:

• Current or recent (within 8 wks) use of medication that could conceivably alter microvascular function [including (but not limited to) stimulants, antihypertensives, HMG-CoA reductase inhibitors]
• Changes or alterations in medication status (starting a new, additional, or different medication or changing the dose of a current medication)
• Unstable or diagnosed chronic clinical disease, including cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological disease (e.g., hypertension, heart disease, diabetes, hyperlipidemia, psoriasis)
• Body mass index <18.5 or >35 kg/m2
• Pregnancy (including a positive urine pregnancy test) or breast-feeding
• Known allergies to pharmacological agents or study drugs
• Non-English-speaking. Participants need to understand English to follow instructions and comply with procedures conducted during the screening and experimental visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: assessment of microvascular endothelial function; The investigators use intradermal microdialysis to deliver acetylcholine, L-NAME, and acetylcholine + L-NAME to the cutaneous microvasculature.	Drug: Acetylcholine; acetylcholine, and acetylcholine + L-NAME (Nitric oxide synthase inhibitor) are locally and acutely delivered to the cutaneous microvasculature to assess endothelium- and nitric oxide-dependent dilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular blood flow response to acetylcholine	cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME	baseline study visit (average of 4 hours)
Microvascular blood flow response to local heat (42 degrees Celsius)	cutaneous vascular vasodilator response to 42 degree local heat; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of lactated Ringer's, followed by L-NAME.	baseline study visit (average of 4 hours)
Microvascular blood flow response to local heat (39 degrees Celsius)	cutaneous vascular vasodilator response to 39 degree local heat; measured with laser-Doppler flowmetry coupled with intradermal microdialysis delivery of lactated Ringer's, followed by L-NAME.	baseline study visit (average of 4 hours)

Collaborators and Investigators

• Sponsor: University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Actual): August 12, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Vasodilator Agents; Cholinergic Agents; Cholinergic Agonists; Acetylcholine
• Other Study ID Numbers: 202404816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No