Endothelial Derived Hyperpolarization Factor and Vascular Control

NCT05176379 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 14056
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Most cardiometabolic diseases are characterized by increased muscle sympathetic nerve activity (MSNA) during rest and exercise which contributes to poor health outcomes. In healthy humans during muscle contraction, there is a blunting of skeletal muscle vascular responsiveness to increases in MSNA. However, the exact mechanisms involved are unknown although, best evidence suggests that the mechanism is endothelium derived, but nitric oxide (NO) and prostaglandin (PG) independent. Endothelium-derived hyperpolarizing factor (EDHF) is a NO and PG independent vasodilator in both cerebral and skeletal muscle circulations, however, it is unknown if EDHF contributes to vascular responsiveness during elevated MSNA. The application of lower body negative pressure (LBNP) is a safe and non-invasive manipulation that can be used to increase MSNA causing vasoconstriction in humans. Therefore, the purpose of this experiment is to determine if acute inhibition of EDHF alters central and peripheral vascular responses to LBNP at rest and during dynamic exercise. Thereby, providing evidence by which EDHF contributes to vascular control in healthy humans and identify it's potential as a therapeutic target for cardiometabolic diseases that are characterized by elevated MSNA

Conditions

Healthy

Keywords

brain blood flow; muscle blood flow; endothelial function

Outcome Measures

Primary Outcomes (2)

• Near-Infrared Spectroscopy

  Concentrations of Oxygen, deoxy, and Total Hemoglobin (micro molar)

  up to 4 hours

• Transcranial Doppler Ultrasound

  middle cerebral artery blood velocity

  up to 4 hours

Secondary Outcomes (2)

• Wireless electrocardiogram

  up to 4 hours

• Finger photoplethysmography

  up to 4 hours

Study Arms (2)

fluconazole

EXPERIMENTAL

fluconazole tablet/pill 150 mg, single acute dose

Drug: Fluconazole 150 mg

Placebo

PLACEBO COMPARATOR

250 mg pill microcrystalline Cellulose, single acute dose

Drug: Fluconazole 150 mg

Interventions

Fluconazole 150 mg DRUG

A single acute 150 mg dose

Also known as: placebo

Placebo; fluconazole

Eligibility Criteria

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

You may qualify if:

• Normotensive (systolic blood pressure \< 130 mmHg and/or diastolic blood pressure \< 85 mmHg) individuals
• Individuals free of cardiovascular disease and metabolic disease
• Individuals free of any form of autonomic dysfunction
• Individuals with a BMI under 30 kg/m²
• Women that are premenopausal with a regular menstrual cycle (26-30 days)

You may not qualify if:

• Smokers, tobacco users (regular use in the last 6 months)
• Individuals with a blood pressure greater than 130/85
• Subjects who use Amiodarone, Sulphaphenazole
• Subjects who use S-warfarin, Tolbutamine, Phenytoin, Lonafarnib
• Cardiometabolic medication use (e.g. anti-hypertensives, insulin-sensitizing, statins)
• Sex hormone replacement medical use (e.g. testosterone, estrogen, progesterone)
• Pregnancy

Sponsors & Collaborators

• University of Oklahoma: lead

Study Sites (1)

Department of Health and Exercise Science

Norman, Oklahoma, 73019, United States

RECRUITING

MeSH Terms

Interventions

Fluconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jeremy M Kellawan, PhD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeremy M Kellawan, PhD

CONTACT

4053259028; kellawan@ou.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will receive a placebo instead of fluconazole
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, single-blind, Placebo controlled, crossover design

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: January 4, 2022
• Study Start: February 19, 2022
• Primary Completion: December 1, 2024
• Study Completion: May 1, 2025
• Last Updated: July 23, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)