Clinical trial NCT05001048: Sex Differences in Sympathetic Activity and Vascular Reactivity During Acute and Chronic Hypoxia.
Official title: Sex Differences in Sympathetic Activity and Vascular Reactivity During Acute and Chronic Hypoxia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vasodilation
Vasoconstriction
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2021-08-11
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

Detailed description: About 200 million people worldwide live at high altitudes. Millions of others travel to high altitude every year for work or travel. The low oxygen (or hypoxia) experienced at high altitudes causes considerable physiological stress, and the body adapts in order to maintain adequate oxygen delivery to its tissues. One of these adaptations is an increase in the activity of the sympathetic nervous system. This system is responsible for the "fight or flight" response. Sympathetic activity regulates the size of the blood vessels, which will affect blood pressure. Previous studies suggest that males and females regulate their blood pressure in different ways. Females tend to have lower resting sympathetic activity, and less vasoconstriction in response to stressors than males. Blood pressure changes are also influenced by levels of sex hormones; for example, estrogen may cause opposing vasodilation. Therefore, it is important to understand the differences in how males and females respond to low oxygen.

The main purpose of this study is to examine the differences between males and females in control of blood vessels during exposure to low oxygen. To study this question, we will test vasoreactivity to set physiological stressors in both males and females. Participants will be recruited at the Canadian sites, and we will test them while they breathe low oxygen for a short amount of time at low altitude. We will also perform assessments on the same participants during a two week stay at high altitude at White Mountain, CA, which is at an altitude of 3,800m. These data will have implications in the basic understanding of differences between male and female physiology. Specifically, to males and females living or travelling to high altitude.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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)
* Have a history of smoking regularly in the last 6 months (but nicotine substitutes (patch, gum) not an exclusion criteria)
* Those with a known allergy to sulfites
* Participants taking monoamine oxidase (MAO) inhibitors or tricyclic antidepressants

Primary outcomes:
measure: Change in blood pressure
timeFrame: 18 minutes
measure: Change in arterial blood flow
timeFrame: 18 minutes
measure: Cold pressor test reactivity
timeFrame: 4 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Mount Royal University
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: Sean van Diepen, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Craig Steinback, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.