Comparing Approaches to Assess Nitric Oxide-dependent Cutaneous Vasodilation

NCT06499844 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 202404816
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Endothelial Function

Outcome Measures

Primary Outcomes (3)

• 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)

Study Arms (1)

assessment of microvascular endothelial function

EXPERIMENTAL

The investigators use intradermal microdialysis to deliver acetylcholine, L-NAME, and acetylcholine + L-NAME to the cutaneous microvasculature.

Drug: Acetylcholine

Interventions

Acetylcholine DRUG

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

assessment of microvascular endothelial function

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• men and women
• years of age

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Interventions

Acetylcholine

Intervention Hierarchy (Ancestors)

Biogenic Amines; Amines; Organic Chemicals

Central Study Contacts

Anna Stanhewicz, PhD

CONTACT

3194671732; anna-stanhewicz@uiowa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: All participants will complete one laboratory visit to assess endothelial function in the cutaneous microvasculature.

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: July 15, 2024
• Study Start: August 1, 2024
• Primary Completion: August 12, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)