VasodilationNCT05525416
Sex Differences in Sympathetic Vascular Reactivity at High Altitude
A study testing Sodium Nitroprusside, Phenylephrine Hydrochloride and Norepinephrine in people with Vasodilation and Vasoconstriction, run by University of Alberta at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Vasodilation, Vasoconstriction
- What is being tested?
- Sodium Nitroprusside, Phenylephrine Hydrochloride and Norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesCanada
- Study dates
- 28 Jul 2022to 5 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Between ages of 18-50
- No medical history of cardiovascular, respiratory, nervous system, or metabolic disease
- Females must be pre-menopausal
Who cannot join
- 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)
- Participants who are current daily smokers
Show all 9Show fewer
- Those with a known allergy to sulfites
- Participants taking monoamine oxidase (MAO) inhibitors or tricyclic antidepressants or other medications that have contraindications with the study drugs
- Participants who are still within the washout period from participating in other studies involving drugs.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
University of Alberta
Edmonton, Alberta, T6G 2R3
University of British Columbia - Okanagan
Kelowna, British Columbia, V1V 1V7
About this study
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.
Read the detailed description
About 200 million people worldwide live at high altitudes and millions of others travel to high altitude every year for work or pleasure. At high altitude participants are exposed to a lower than normal level of oxygen, also known as hypoxia. This causes stress to the human body, which will adapt in order to maintain adequate oxygen delivery to its tissues. One of these adaptations is an increase in activity of participants' sympathetic nervous system ("fight or flight" response). Sympathetic nerve activity affects the size of participants' blood vessels, which in turn will affect blood pressure. Men and women regulate their blood pressure in different ways; for example, women tend to have lower blood pressure and sympathetic nerve activity than men. Women also appear to have less constriction of their blood vessels in response to stress. This may be in part because estrogen causes blood vessels to dilate. It may also be due to differences in the receptors which are activated by the sympathetic nervous system. These receptors are called alpha and beta receptors and respond to sympathetic nerve activity in opposite directions. Women represent 50% of the population living at and travelling to high altitude, therefore, it is important to understand the differences in how men and women respond to low oxygen.
The main purpose of this study is to examine the differences between men and women in the sympathetic nervous system control of blood vessels during exposure to low oxygen. To study this question, the investigators will test how blood vessels respond to stressors in both men and women. Participants will be recruited at the Canadian sites, and the investigators will test them while they breathe low oxygen for a short amount of time at low altitude. The investigators 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.
- Conditions
- Vasodilation, Vasoconstriction
- Being tested
- Sodium Nitroprusside, Phenylephrine Hydrochloride, Norepinephrine, Isometric Handgrip and Post-Exercise Circulatory Occlusion, Rhythmic Handgrip
- Medical subject headings
- Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium NitroprussideDrug
A bolus injection of sodium nitroprusside will be given to lower blood pressure and evaluate baroreflex function.
Phenylephrine HydrochlorideDrug
Also called Neo-Synephrine
A bolus injection of phenylephrine will be given to raise blood pressure and evaluate baroreflex function immediately following the sodium nitroprusside infusion.
Phenylephrine HydrochlorideDrug
Investigators will give three incremental doses via brachial artery catheter to observe α1-adrenoreceptor mediated vasoconstriction. This will occur three times throughout the protocol.
NorepinephrineDrug
Investigators will give three incremental doses via brachial artery catheter to observe adrenoreceptor activation. This will occur three times throughout the protocol.
Isometric Handgrip and Post-Exercise Circulatory OcclusionOther
Participants will perform 2 minutes of isometric handgrip at 30% maximal voluntary contraction followed by 2 minutes of post-exercise circulatory occlusion to assess the reactivity of the blood vessels to exercise and the metaboreflex.
Rhythmic HandgripOther
Participants will perform 3 minutes of rhythmic handgrip at 25% maximal voluntary contraction to assess the reactivity of blood vessels to dynamic exercise.
Cold Pressor TestOther
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.
Propranolol HydrochlorideDrug
Local infusion via brachial artery catheterization will occur continuously for the remainder of the study. Propranolol is a beta-adrenergic antagonist and will allow investigation of the role of beta receptors in responses to various stressors. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion.
Phentolamine MesylateDrug
Local infusion via brachial artery catheterization will occur continuously for the remainder of the study. Phentolamine is an alpha-adrenergic antagonist and will allow investigation the role of alpha receptors in responses to various stressors. It will be continuously infused with propranolol. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion.
| Study group | Role | What they receive |
|---|---|---|
| Low Altitude | Experimental | Participants will be assessed at an altitude of <1050m. Receives: Drug: Sodium Nitroprusside; Drug: Phenylephrine Hydrochloride; Drug: Norepinephrine; Other: Isometric Handgrip and Post-Exercise Circulatory Occlusion; Other: Rhythmic Handgrip; Other: Cold Pressor Test; Drug: Propranolol Hydrochloride; Drug: Phentolamine Mesylate |
| High Altitude | Experimental | Participants will be assessed on a high-altitude expedition at an elevation of 3,800m. Receives: Drug: Sodium Nitroprusside; Drug: Phenylephrine Hydrochloride; Drug: Norepinephrine; Other: Isometric Handgrip and Post-Exercise Circulatory Occlusion; Other: Rhythmic Handgrip; Other: Cold Pressor Test; Drug: Propranolol Hydrochloride; Drug: Phentolamine Mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in systolic, diastolic, and mean arterial blood pressure
modified oxford
Measured: 3 minutes
Change in arterial blood flow
phenylephrine and norepinephrine sensitivity
Measured: 1 hour 30 minutes
Change in vascular conductance
exercise and metaboreflex reactivity
Measured: 20 minutes
Cold pressor test
sympathetic reactivity
Measured: 3 minutes
Propranolol
changes in vascular conductance
Measured: 2 hours
Phentolamine
changes in vascular conductance
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2022
- Study start28 Jul 2022
- Primary completion5 Feb 2023
- Study completion5 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for VasodilationStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- Participants will partake in both arms of the study, which include: 1) low altitude and 2) high altitude assessments.
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sean van Diepen, MD, MSc, Principal investigator, University of AlbertaCraig D Steinback, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05525416
- Sponsor's protocol ID
- Pro00096808
- Status last verified
- Mar 2023
- First submitted
- 22 Jul 2022
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 19171792Mazzeo 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.
PubMed 9516178Purdy 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.
PubMed 30462566Usselman 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.
PubMed 25527774
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex Differences in Sympathetic Vascular Reactivity at High Altitude
- ClinicalTrials.gov ID
- NCT05525416
- Acronym / sponsor ID
- Pro00096808
- Conditions
- Vasodilation, Vasoconstriction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- 28 Jul 2022 (actual)
- Primary completion
- 5 Feb 2023 (actual)
- Study completion
- 5 Feb 2023 (actual)
- First posted
- 1 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 and millions of others travel to high altitude every year for work or pleasure. At high altitude participants are exposed to a lower than normal level of oxygen, also known as hypoxia. This causes stress to the human body, which will adapt in order to maintain adequate oxygen delivery to its tissues. One of these adaptations is an increase in activity of participants' sympathetic nervous system ("fight or flight" response). Sympathetic nerve activity affects the size of participants' blood vessels, which in turn will affect blood pressure. Men and women regulate their blood pressure in different ways; for example, women tend to have lower blood pressure and sympathetic nerve activity than men. Women also appear to have less constriction of their blood vessels in response to stress. This may be in part because estrogen causes blood vessels to dilate. It may also be due to differences in the receptors which are activated by the sympathetic nervous system. These receptors are called alpha and beta receptors and respond to sympathetic nerve activity in opposite directions. Women represent 50% of the population living at and travelling to high altitude, therefore, it is important to understand the differences in how men and women respond to low oxygen.
The main purpose of this study is to examine the differences between men and women in the sympathetic nervous system control of blood vessels during exposure to low oxygen. To study this question, the investigators will test how blood vessels respond to stressors in both men and women. Participants will be recruited at the Canadian sites, and the investigators will test them while they breathe low oxygen for a short amount of time at low altitude. The investigators 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will partake in both arms of the study, which include: 1) low altitude and 2) high altitude assessments.
| Arm | Type | Receives |
|---|---|---|
| Low Altitude | Experimental | Drug: Sodium Nitroprusside, Drug: Phenylephrine Hydrochloride, Drug: Norepinephrine, Other: Isometric Handgrip and Post-Exercise Circulatory Occlusion, Other: Rhythmic Handgrip, Other: Cold Pressor Test, Drug: Propranolol Hydrochloride, Drug: Phentolamine MesylateParticipants will be assessed at an altitude of <1050m. |
| High Altitude | Experimental | Drug: Sodium Nitroprusside, Drug: Phenylephrine Hydrochloride, Drug: Norepinephrine, Other: Isometric Handgrip and Post-Exercise Circulatory Occlusion, Other: Rhythmic Handgrip, Other: Cold Pressor Test, Drug: Propranolol Hydrochloride, Drug: Phentolamine MesylateParticipants will be assessed on a high-altitude expedition at an elevation of 3,800m. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Between ages of 18-50
- No medical history of cardiovascular, respiratory, nervous system, or metabolic disease
- Females must be pre-menopausal
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium NitroprussideA bolus injection of sodium nitroprusside will be given to lower blood pressure and evaluate baroreflex function. | Drug | High Altitude, Low Altitude |
| Phenylephrine HydrochlorideAlso: Neo-SynephrineA bolus injection of phenylephrine will be given to raise blood pressure and evaluate baroreflex function immediately following the sodium nitroprusside infusion. | Drug | High Altitude, Low Altitude |
| Phenylephrine HydrochlorideInvestigators will give three incremental doses via brachial artery catheter to observe α1-adrenoreceptor mediated vasoconstriction. This will occur three times throughout the protocol. | Drug | High Altitude, Low Altitude |
| NorepinephrineInvestigators will give three incremental doses via brachial artery catheter to observe adrenoreceptor activation. This will occur three times throughout the protocol. | Drug | High Altitude, Low Altitude |
| Isometric Handgrip and Post-Exercise Circulatory OcclusionParticipants will perform 2 minutes of isometric handgrip at 30% maximal voluntary contraction followed by 2 minutes of post-exercise circulatory occlusion to assess the reactivity of the blood vessels to exercise and the metaboreflex. | Other | High Altitude, Low Altitude |
| Rhythmic HandgripParticipants will perform 3 minutes of rhythmic handgrip at 25% maximal voluntary contraction to assess the reactivity of blood vessels to dynamic exercise. | Other | High Altitude, Low Altitude |
| Cold Pressor TestStandardized sympathetic stressor involving submersion of the hand in ice-cold water for 3-minutes, aiming to elicit endogenous neurotransmitter release and blood pressure increases. | Other | High Altitude, Low Altitude |
| Propranolol HydrochlorideLocal infusion via brachial artery catheterization will occur continuously for the remainder of the study. Propranolol is a beta-adrenergic antagonist and will allow investigation of the role of beta receptors in responses to various stressors. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion. | Drug | High Altitude, Low Altitude |
| Phentolamine MesylateLocal infusion via brachial artery catheterization will occur continuously for the remainder of the study. Phentolamine is an alpha-adrenergic antagonist and will allow investigation the role of alpha receptors in responses to various stressors. It will be continuously infused with propranolol. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion. | Drug | High Altitude, Low Altitude |
Primary outcome
Change in systolic, diastolic, and mean arterial blood pressure
Time frame: 3 minutes
modified oxford
Change in arterial blood flow
Time frame: 1 hour 30 minutes
phenylephrine and norepinephrine sensitivity
Change in vascular conductance
Time frame: 20 minutes
exercise and metaboreflex reactivity
Cold pressor test
Time frame: 3 minutes
sympathetic reactivity
Propranolol
Time frame: 2 hours
changes in vascular conductance
Phentolamine
Time frame: 1 hour
changes in vascular conductance
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 19171792Hart 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.
- Background: PubMed 9516178Mazzeo 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.
- Background: PubMed 30462566Purdy 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.
- Background: PubMed 25527774Usselman 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.
Related trials for Vasodilation
Active, not recruitingEarly Phase 1
Comparing Approaches to Assess Nitric Oxide-dependent Cutaneous Vasodilation
Endothelial Function
RecruitingPhase 4
DECONGEST-AHF: Vasodilatation or Loop Diuretics in Acute Heart Failure
Pulmonary Edema, Congestive Heart Failure
RecruitingEarly Phase 1
Impact of Early Aging and Menopause on the Vascular Responses to Hypoxia
Aging, Menopause
RecruitingPhase 2
The Mito-Frail Trial: Effects of MitoQ on Vasodilation, Mobility and Cognitive Performance in Frail Older Adults
Frailty, Mild Cognitive Impairment
RecruitingEarly Phase 1
Sex Disparities in Hypoxic Vasodilation and Impact of Obesity
Obesity, Vasodilation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sean van Diepen, MD, MSc principal investigator
University of Alberta
Craig D Steinback, PhD principal investigator
University of Alberta
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sodium Nitroprusside, Phenylephrine Hydrochloride and Norepinephrine in people with Vasodilation and Vasoconstriction, run by University of Alberta at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in systolic, diastolic, and mean arterial blood pressure (time frame: 3 minutes). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05525416, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.