Sex Differences in Sympathetic Activity and Vascular Reactivity During Acute and Chronic Hypoxia.

NCT05001048 | Completed DMC

• 1 other identifier: Pro00088122
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to investigate sex differences in blood pressure control associated with exposure to acute hypoxia (low oxygen), and short term acclimatization to hypoxia at high altitude.

Conditions

Vasodilation; Vasoconstriction

Outcome Measures

Primary Outcomes (3)

• Change in blood pressure

  Phenylephrine sensitivity

  18 minutes

• Change in arterial blood flow

  Phenylephrine sensitivity

  18 minutes

• Cold pressor test reactivity

  4 minutes

Study Arms (3)

Low Altitude

EXPERIMENTAL

Participants will be assessed at an altitude of \<1050m.

Drug: Phenylephrine Hydrochloride; Other: Cold Pressor Test; Other: Isocapnic Acute Hypoxia

Early Acclimatization to High Altitude

EXPERIMENTAL

Participants will be assessed on day 2 or 3 of a high-altitude expedition at 3,800m.

Drug: Phenylephrine Hydrochloride; Other: Cold Pressor Test; Other: Hyperoxia

Late Acclimatization to High Altitude

EXPERIMENTAL

Participants will be assessed on day 9 or 10 of a high-altitude expedition at 3,800m.

Drug: Phenylephrine Hydrochloride; Other: Cold Pressor Test; Other: Hyperoxia

Interventions

Phenylephrine Hydrochloride DRUG

Series of three incremental bolus injections to observe α1-adrenoreceptor mediated vasoconstriction.

Also known as: Neo-Synephrine

Early Acclimatization to High Altitude; Late Acclimatization to High Altitude; Low Altitude

Cold Pressor Test OTHER

Standardized sympathetic stressor involving submersion of the hand in ice-cold water for 3-minutes, aiming to elicit endogenous neurotransmitter release and blood pressure increases.

Early Acclimatization to High Altitude; Late Acclimatization to High Altitude; Low Altitude

Isocapnic Acute Hypoxia OTHER

During low altitude assessment, participants will be exposed to isocapnic hypoxia equivalent to 3,800m to assess responses to acute exposure.

Low Altitude

Hyperoxia OTHER

During high altitude assessments, participants will breathe an oxygen concentration comparable to their end-tidal values at low altitude for the assessment of the influences of acclimatization.

Early Acclimatization to High Altitude; Late Acclimatization to High Altitude

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Between ages of 18-50
• No medical history of cardiovascular, respiratory, nervous system, or metabolic disease
• Females must be pre-menopausal

You may not qualify if:

• Any known cardiovascular, respiratory, nervous system, or metabolic disease (however, participants with controlled arterial hypertension will not be excluded)
• Having travelled above 2,000m within 1 month of testing at low and high altitude
• Females who are pregnant, confirmed by a pregnancy test
• Females who are post-menopausal
• Participants that are classified as obese (body mass index \> 30kg⋅m²)
• Those with a known allergy to sulfites
• Participants taking monoamine oxidase (MAO) inhibitors or tricyclic antidepressants

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (2)

Mount Royal University

Calgary, Alberta, T3E 6K6, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

Related Publications (4)

• Hart EC, Charkoudian N, Wallin BG, Curry TB, Eisenach JH, Joyner MJ. Sex differences in sympathetic neural-hemodynamic balance: implications for human blood pressure regulation. Hypertension. 2009 Mar;53(3):571-6. doi: 10.1161/HYPERTENSIONAHA.108.126391. Epub 2009 Jan 26.

  PMID: 19171792 BACKGROUND

• Mazzeo RS, Child A, Butterfield GE, Mawson JT, Zamudio S, Moore LG. Catecholamine response during 12 days of high-altitude exposure (4, 300 m) in women. J Appl Physiol (1985). 1998 Apr;84(4):1151-7. doi: 10.1152/jappl.1998.84.4.1151.

  PMID: 9516178 BACKGROUND

• Purdy GM, James MA, Rees JL, Ondrus P, Keess JL, Day TA, Steinback CD. Spleen reactivity during incremental ascent to altitude. J Appl Physiol (1985). 2019 Jan 1;126(1):152-159. doi: 10.1152/japplphysiol.00753.2018. Epub 2018 Nov 21.

  PMID: 30462566 BACKGROUND

• Usselman CW, Gimon TI, Nielson CA, Luchyshyn TA, Coverdale NS, Van Uum SH, Shoemaker JK. Menstrual cycle and sex effects on sympathetic responses to acute chemoreflex stress. Am J Physiol Heart Circ Physiol. 2015 Mar 15;308(6):H664-71. doi: 10.1152/ajpheart.00345.2014. Epub 2014 Dec 19.

  PMID: 25527774 BACKGROUND

MeSH Terms

Conditions

Aneurysm

Interventions

Phenylephrine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Sean van Diepen, MD, MSc

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Craig Steinback, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Due to the study design, masking is not possible. The time points and dosages of the study drug will be known to the participant. Further, due to the wash-out time of the acute hypoxia/hyperoxia interventions, these will always be completed second to the interventions breathing room air.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will partake in all three arms of the study, which include: 1) low altitude, 2) early acclimatization, and 3) late acclimatization to high altitude assessments.

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: August 11, 2021
• Study Start: August 4, 2019
• Primary Completion: December 7, 2021
• Study Completion: September 9, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

CA (2)