Recruiting

Observational Study

Sponsor:

University of Alberta

Code:

NCT05997732

Conditions

Vasoconstriction

Vasodilation

Eligibility Criteria

Sex: All

Age: 18 - 40

Healthy Volunteers: Accepted

Interventions

Phenylephrine Hydrochloride

Isoproterenol Hydrochloride

Norepinephrine Bitartrate

Propranolol Hydrochloride

Phentolamine Mesylate

Study Details

Brief summary:

The main purpose of this interventional study is to examine differences in resting blood pressure control between healthy males and females. The main questions it aims to answer are:

1. Are there sex differences in the communication between the sympathetic nervous system (also known as the "fight or flight" response) and peripheral blood vessels (which influence systemic blood pressure)?
2. What is the role of specific vascular receptors that respond to sympathetic signals, and is it different between males and females?

Participants will complete one study visit of approximately 3 hours where they will:

  • Have a blood sample taken to measure circulating sex hormone and sympathetic transmitters.
  • Receive very small doses of medications commonly used to adjust blood pressure through an artery in their arm. The effects of these medications will be short-acting and localized to the forearm.
  • Have their sympathetic nervous activity directly measured through two very small needles (similar to acupuncture needles) in the side of their leg.
  • Have their blood pressure and heart rate recorded, and forearm blood flow measured using ultrasound.

Conditions

Vasoconstriction

Vasodilation

Study ID

NCT05997732

Start date

Oct 31, 2023

Status verified date

Jan, 2026

Completion date

Dec 1, 2027

Anticipated

Primary completion date

Dec 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 40

Healthy Volunteers: Accepted

Inclusion Criteria:

  • Between ages 18-40 years
  • No diagnosed medical history of cardiovascular, respiratory, nervous system, or metabolic disease.
  • Females must be pre-menopausal.
  • Prior to study visit: abstained from caffeine, alcohol, strenuous exercise, and medication not taken regularly for at least 12 hours.

Exclusion Criteria:

  • Current diagnosis of cardiovascular, respiratory, nervous system, or metabolic disease that may impact blood pressure regulation. This will be assessed on a case-by-case basis by the study physician.
  • Participants with bleeding or clotting disorders, or those currently taking blood thinners.
  • Participants currently taking beta-agonist inhalers i.e. Ventolin (at least not in the last 24 hours).
  • Females who are pregnant, confirmed by a pregnancy test.
  • Females who have are less than 1 year postpartum or are breastfeeding.
  • Females who are post-menopausal.
  • Participants that are classified as obese (body mass index > 30 kg ⋅ m2).
  • Have a history of smoking regularly in the last 6 months (but nicotine substitutes (i.e. patch, gum) are not an exclusion criteria).
  • Those with a known allergy to sulfites, or other components of the supplied solution of study drugs.
  • Participants taking medications that are contraindicated with any of the study drugs, such as monoamine oxidase (MAO) inhibitors or tricyclic antidepressants.
  • Participants who have not adhered to the pre-testing guidelines related to diet, alcohol or exercise will not be excluded, but will be rescheduled for a different day. This is to reduce experimental variability.

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Control Condition

Normal saline will be infused through the brachial artery catheter at the same calculated rate as propranolol + phentolamine in the α+β-blockade condition to control for volumetric effects.

experimental: β-Adrenergic Blockade

β-adrenoreceptors will be blocked locally in the forearm using propranolol. Normal saline will be co-infused at the calculated rate of phentolamine in the α+β-blockade condition to control for volumetric effects.

experimental: α+β-Adrenergic Blockade

α-adrenoreceptors will be blocked locally in the forearm using phentolamine. Propranolol will be co-infused to maintain β-blockade.

Interventions

Phenylephrine Hydrochloride

Participants will receive three incremental doses via the brachial artery catheter to assess α1-adrenoreceptor mediated vasoconstriction.

Isoproterenol Hydrochloride

Participants will receive four incremental doses via the brachial artery catheter to assess β-adrenoreceptor mediated vasodilation.

Norepinephrine Bitartrate

Participants will receive three incremental doses via the brachial artery catheter to assess nonspecific adrenoreceptor activation.

Propranolol Hydrochloride

Propranolol will be continuously infused through the brachial artery catheter to induce β-adrenergic blockade locally in the forearm.

Phentolamine Mesylate

Phentolamine will be continuously infused through the brachial artery catheter to induce α-adrenergic blockade locally in the forearm.

Phenylephrine Hydrochloride

Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the α-adrenergic blockade.

Isoproterenol Hydrochloride

Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the β-adrenergic blockade.

Propranolol Hydrochloride

Propranolol will be continuously co-infused with phentolamine to maintain the β-adrenergic blockade.

Primary outcome measure

  • Forearm blood flow [ Time Frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes ]
  • Forearm vascular resistance [ Time Frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes ]
  • Forearm vascular conductance [ Time Frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes ]
  • Arterial blood pressure [ Time Frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes ]
  • Muscle sympathetic nerve activity [ Time Frame: 10 minutes per condition = 30 minutes ]
  • Circulating sex hormone concentrations [ Time Frame: 2 minutes ]
  • Circulating sympathetic neurotransmitter concentrations [ Time Frame: 2 minutes ]

Central Contacts and Locations

Central contacts

Emily Vanden Berg, MSc

(780)-492-5553ervanden@ualberta.ca

Nicholas Cheung, MSc

(780)-492-5553nkcheung@ualberta.ca

Locations

University of Alberta

Recruiting

Edmonton, Alberta, Canada, T6G 2R3

Contacts

Craig Steinback, PhD

(780)492-5553craig.steinback@ualberta.ca

More Information

Sponsor

University of Alberta

Last update posted

Jan 8, 2026

Last verified

Jan, 2026

Keywords

  • sympathetic nerve activity
  • sex differences
  • adrenergic receptors
  • neurovascular transduction

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Alberta on 2026-01-08.