Clinical trial NCT04928183: The Impact of Carbon Monoxide and Altitude on Vascular Function
Official title: The Impact of Carbon Monoxide and Altitude on Vascular Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vasodilation
Vasoconstriction
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2021-06-16
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will partake in both room air and CO exposure on 2 separate visits.
Primary purpose: BASIC_SCIENCE

Brief summary: The CarMA (Carbon Monoxide and Altitude) Study aims to observe the vascular effects of carbon monoxide exposure at low and high altitudes.

Detailed description: Each year, millions of people make journeys from low altitude regions to high altitude for recreation, travel, and religious pilgrimage. Carbon monoxide (CO) is commonly associated with cigarette smoke, exhaust fumes, and is viewed as a life-threatening toxic gas. Exposure to CO occurs during travel to and during activities common in high-altitude travel and pilgrimage including vehicle fumes, incense, and second-hand smoke exposure. High altitude exposure and CO exposure have been observed independently to have complex and opposing effects on vascular endothelial function. Observation of these stimuli together in a controlled environment may allow for further understanding of the underlying mechanisms of vascular physiology and adaptations to both high-altitude and CO exposure. The CarMA (Carbon Monoxide and Altitude) Study aims to observe the vascular effects of carbon monoxide exposure at low and high altitudes. Recently, other studies have showed a significant improvement in flow mediated dilation (FMD) with acute exposure to low levels of CO To date, no research has been presented concerning the effect of CO on vascular function at altitude. The present study aims to observe the effect of acute carbon monoxide exposure on 1) flow mediated dilation, 2) conduit artery flow in exercise induced reactive hyperemia at sea level and at altitude, and 3) the effect of CO on vascular function in a high altitude dwelling (sherpa) population.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Participants with any known cardiovascular, respiratory, nervous system, or metabolic disease.
* Having travelled above 2,000m within 1 month of testing at low and high altitude.
* Women who are pregnant, confirmed by a pregnancy test.
* Women who are post-menopausal.
* Participants that are classified as obese (body mass index \> 30 kg/m2).
* Participants who are current daily smokers.
* Participants that are currently taking monoamine (MAO) inhibitors, or tricyclic antidepressants.

Primary outcomes:
measure: Change in brachial artery diameter (assessed via ultrasound) following release of arterial occlusion
timeFrame: 15 minutes
measure: Blood flow within the brachial artery during rhythmic handgrip exercise.
timeFrame: 15 minutes
measure: Change in brachial artery conductance following an infusion of phenylephrine
timeFrame: 5 min
Secondary outcomes:
Other outcomes:
Locations:
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:
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citation: Choi BG, Lee J, Kim SW, Lee MW, Baek MJ, Ryu YG, Choi SY, Byun JK, Mashaly A, Park Y, Jang WY, Kim W, Choi JY, Park EJ, Na JO, Choi CU, Lim HE, Kim EJ, Park CG, Seo HS, Oh DJ, Rha SW. The association of chronic air pollutants with coronary artery spasm, vasospastic angina, and endothelial dysfunction. Coron Artery Dis. 2018 Jun;29(4):336-343. doi: 10.1097/MCA.0000000000000603.
citation: Weber LP, Al-Dissi A, Marit JS, German TN, Terletski SD. Role of carbon monoxide in impaired endothelial function mediated by acute second-hand tobacco, incense, and candle smoke exposures. Environ Toxicol Pharmacol. 2011 May;31(3):453-9. doi: 10.1016/j.etap.2011.02.008. Epub 2011 Feb 26.
citation: Tymko MM, Tremblay JC, Bailey DM, Green DJ, Ainslie PN. The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations. J Physiol. 2019 Dec;597(24):5759-5776. doi: 10.1113/JP277191. Epub 2019 Nov 28.