Heat, Microvascular Function and Aging

NCT06633198 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: PRO00052867
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Vascular dysfunction is a common factor in many chronic debilitating diseases, contributing to morbidity and mortality. With the onset of chronic disease or exposure to stress, the vasculature displays an inability to adequately respond to increased blood flow demands, manifesting in a reduced ability or altered mechanism of vasodilation. Aging is an independent risk factor in the development of cardiovascular disease, and reduces vasodilator capacity, or alters the mechanism by which vasodilation occurs in multiple vascular beds. Chronic exercise/physical activity is one of the most potent ways to enhance vascular function, resulting in favorable outcomes such as reductions in blood pressure, and improved ability to perform activities of daily living. Barriers to exercise or failure of long-term adherence preclude many populations from the cardiovascular benefits of exercise, thus further enhancing cardiovascular risk. Avenues to mimic blood flow patterns observed with exercise may exert beneficial effects without the need for the ability to exercise. Recent evidence has demonstrated that passive heat therapy, or chronic heat exposure (\~ +1°C in core temperature) results in reductions in major adverse cardiovascular events, blood pressure and improved large artery endothelial function, primarily through preservation of large artery function in response to vascular stress. It is unclear whether microvascular function is augmented in response to acute heat exposure, or whether this can protect against vascular insults particularly in older adults. Some preliminary evidence in humans suggest that autophagy, a cell recycling process is involved in the beneficial cardiovascular effects, as short-term heat exposure upregulates markers of autophagy. Previous evidence from our lab indicates that autophagy governs the mechanism by which microvascular vasodilation occurs. The role of autophagy in mediating the beneficial effects of passive heating is unknown.

Conditions

Aging

Keywords

Passive heating; Aging; Microvascular; Autophagy

Outcome Measures

Primary Outcomes (1)

• Change in cutaneous microvascular function

  Change in cutaneous microvascular function assessed via microdialysis infusion of acetylcholine (dose response) in the presence and absence of L-NAME to test the dependency upon NO to elicit vasodilation.

  Baseline, 60 minutes post I/R, and 60 minutes post hot water immersion + I/R injury

Secondary Outcomes (3)

• Spontaneous baroreflex sensitivity

  Baseline, 60 minutes post I/R, 60 minutes post hot water immersion + I/R injury

• 24-hour (Ambulatory) Blood Pressure

  Baseline

• Change in plasma concentration of heat shock proteins

  Baseline and 60 minutes post hot water immersion

Study Arms (1)

Passive Heating of lower limbs

EXPERIMENTAL

The lower limbs will be immersed in warm circulating water for 60 minutes.

Procedure: Passive Heating; Drug: L-NAME

Interventions

Passive Heating PROCEDURE

The lower limbs will be immersed in warm (42C) circulating water for 60 minutes.

Passive Heating of lower limbs

L-NAME DRUG

L-NAME will be used during measurement of cutaneous microvascular function to test the dependency upon NO to elicit vasodilation.

Passive Heating of lower limbs

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be between 18-80 yrs. of age

You may not qualify if:

• Cardiovascular Risk Factors
• Uncontrolled/unmanaged hypertension and/or use of current anti-hypertensive therapy
• Current Tobacco product use or within last 6 months
• BMI greater than 30
• Hyperlipidemia - diagnosed and/or taking medications to manage
• Hypercholesterolemia - diagnosed and/or taking medications to manage (e.g. statins)
• Type 1 or Type 2 Diabetes
• Use of anti-coagulant or anti-platelet drugs
• Use of beta blockers
• Symptomatic coronary artery disease
• Diagnosed Heart Failure (Any classification above Class I as defined by NY Heart Association)
• Diagnosed renal impairment Renal impairment defined, according to National Kidney Foundation as abnormalities of kidney structure or function, present for greater than 3 months, including:
• Albuminuria (ACR ≥ 30 mg/g)
• Urine sediment abnormalities
• Electrolyte and other abnormalities due to tubular disorders

Sponsors & Collaborators

• William Hughes: lead

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Interventions

NG-Nitroarginine Methyl Ester

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Central Study Contacts

William E Hughes, Ph.D.

CONTACT

414-955-7519; whughes@mcw.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: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: October 9, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 30, 2025

Record last verified: 2025-04

Locations

US (1)