DyspneaNCT05619887
Muscle Reflex Inhibition in Hypoxic Exercise
A study testing Fentanyl and Saline in people with Dyspnea and Muscle Strain, run by University of British Columbia at 1 site in Canada.
Trial summary
The goal of this interventional study is to compare muscle reflex function under settings of normoxia (normal oxygen level), acute hypoxia (brief oxygen-lack) and chronic hypoxia (long-duration exposure to oxygen-lack). Read more about this study
- Who is it for?
- Ages 19 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Dyspnea, Muscle Strain
- What is being tested?
- Fentanyl and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2023to Jun 2024
- 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 19 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- aged 19 - 40 years old
- not taking medications (exception oral contraception)
- no history of cardiovascular, respiratory or neurological disease
- members of the high altitude expedition to White Mountain in 2023
Who cannot join
- post-menopausal or pregnant
- obese
- current smokers
- taking prescription medications that may affect responses to exercise
- All potential participants will be screened by a physician to identify co-morbidities
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of British Columbia - Okanagan Campus
Kelowna, British Columbia, V1V1V7
Philip N Ainslie, PhD, 250.807.8089, philip.ainslie@ubc.ca
Neil Eves, PhD, 250.807.9676, neil.eves@ubc.ca
About this study
Official title: Effect of Muscle Reflex Inhibition on Cardiorespiratory Responses to Exercise in Hypoxia
The goal of this interventional study is to compare muscle reflex function under settings of normoxia (normal oxygen level), acute hypoxia (brief oxygen-lack) and chronic hypoxia (long-duration exposure to oxygen-lack).
The main question is: Does the muscle reflex adapt to chronic hypoxia?
Young, healthy participants will complete light-to-high intensity cycling exercise with and without suppression of the muscle reflex. Suppression of the muscle reflex will be via spinal administration of the opioid Fentanyl. In the control condition, saline will be administered into the spinal space. Participants will complete control (saline) and experimental (Fentanyl) exercise conditions at sea-level (Kelowna, BC, Canada) breathing room air and whilst breathing a lower fraction of oxygen (acute hypoxia). Thereafter, participants will complete the exercise test after living at high altitude (White Mountain, CA, USA) for 2 weeks whilst breathing room air (chronic hypoxia) and breathing a higher fraction of oxygen (restored normoxia).
Read the detailed description
Purpose:
To determine whether muscle reflex control of cardiorespiratory function is sensitized by chronic exposure to low oxygen environments. To do this, fentanyl will be administered into the lumbar spine to suppress nerve activity coming from the muscle during upright cycling exercise.
Hypothesis:
Cardiorespiratory responses (ventilation, blood pressure and heart rate) to cycling exercise will be suppressed when muscle reflex activity is partially blocked with fentanyl administration. This suppression will be augmented in a dose-dependent manner with the duration of hypoxic exposure.
Design:
This is a repeated measures cross-over design with participants completing control (saline) and experimental (fentanyl) conditions both low and high altitude; a total of six visits is required. Sea level testing sessions will involve a cycling exercise bout while breathing room air and a second exercise bout breathing a hypoxic gas mixture meant to simulate the altitude at White Mountain. High altitude testing sessions will involve the same cycling exercise bout while breathing room air and another exercise bout while breathing a hyperoxic gas mixture meant to simulate the altitude in Kelowna. Cardiorespiratory (ventilation, blood pressure and heart rate) will be measured throughout with (fentanyl) and without (saline) muscle reflex suppression. A 7-km time trial test will be performed during each visit to determine how the muscle reflex influences exercise performance.
Experimental procedures:
Participants will visit the lab on six occasions; 3 in both Kelowna and White Mountain. Participants will be requested to practice regular exercise and dietary habits that can be easily replicated in the 24 hours prior to every laboratory visit. Exercise and dietary patterns will be documented during the first visit and thereafter the participants will be reminded of these practices and instructed to match them as closely as possible in the 24 hours leading up to all subsequent visits. Participants will only be instructed to avoid heavy exercise in the 12 hours prior to testing sessions. On the first visit (Kelowna), participants will be introduced into the lab, where we will give oral and written instruction detailing the procedures and associated risks related to participating. Details of the experimental visits are outlined below:
Sea level:
- Familiarization and fitness test (1 h) General introduction to the lab, testing equipment and measurements devices. Maximal aerobic power test on an upright cycle ergometer.
- Main experimental visit #1, saline or fentanyl (2 h) Invasive cannulas will be inserted and drugs administered by an anesthetist. Complete four steady-state exercise bouts (3 min each) while breathing room air.
After a 2 min wash-in, complete four steady-state exercise bouts (3 min each) while breathing hypoxic gas (FiO2 = 0.15).
Complete a 7 km time trial test. - Main Experimental visit #2, Intrathecal (spinal) saline or fentanyl (2 h) Complete identical procedures as experimental visit #1, but the opposite condition.
High altitude:
- High altitude fitness test #1 (30 min) Maximal aerobic power test on upright cycle ergometer.
- Main experimental visit #3, saline or fentanyl (2 h) Invasive cannulas will be inserted and drugs administered by an anesthetist. Complete four steady-state exercise bouts (3 min each) while breathing room air.
After a 2 min wash-in, complete four steady-state exercise bouts (3 min each) while breathing hyperoxic gas (FiO2 = 0.30).
Complete a 7 km time trial test.
- Main experimental visit #4, saline or fentanyl (2 h) Complete identical procedures as experimental visit #3, but the opposite condition.
- Conditions
- Dyspnea, Muscle Strain
- Being tested
- Fentanyl, Saline
- Keywords
- Dyspnea, Exercise, Muscle reflex, Type III/IV afferents
- Medical subject headings
- Dyspnea, Sprains and Strains, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FentanylDrug
Also called fentaNYL Citrate
Fentanyl, when administered into the intrathecal (spinal) space suppresses feedback from the muscles below the site of action, i.e., the legs. It does not affect resting cardiorespiratory responses. We are using this to test what role the muscle reflex plays during exercise.
SalineOther
An equal volume (as above) of saline will be administered into the intrathecal (spinal) space. This has no effect of cardiorespiratory responses at rest or during exercise; it is to control for the invasiveness of the procedure required to suppress muscle feedback in the experimental condition.
| Study group | Role | What they receive |
|---|---|---|
| Sea level control | Placebo comparator | Sea level exercise will be completed after the administration of 1 mL of isotonic saline into the intrathecal (spinal) space between L3-L4. Receives: Other: Saline |
| Sea level experimental (muscle reflex suppression) | Experimental | Sea level exercise will be completed after the administration of 0.25 mL of fentanyl into the intrathecal (spinal) space between L3-L4. Receives: Drug: Fentanyl |
| High altitude control | Placebo comparator | High altitude exercise will be completed after the administration of 1 mL of isotonic saline into the intrathecal (spinal) space between L3-L4. Receives: Other: Saline |
| High altitude experimental (muscle reflex suppression) | Experimental | High altitude exercise will be completed after the administration of 0.25 mL of fentanyl into the intrathecal (spinal) space between L3-L4. Receives: Drug: Fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventilation
Ventilation, in liters per minute.
Measured: Data collected during steady-state breathing in the last minute of exercise
Secondary outcomes (1)
Mean arterial blood pressure (entire pressure wave)
Blood pressure, in millimeters of mercury
Measured: Data collected during steady-state breathing in the last minute of exercise
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2022
- Study startJun 2023 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionJun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DyspneaStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will complete all interventions (control and experimental) following drug washout.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Phil Ainslie, University of British Columbia
- Investigators
- Philip N Ainslie, PhD, Principal investigator, University of British Columbia- Okanagan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05619887
- Sponsor's protocol ID
- Muscle_reflex_hypoxia
- Status last verified
- Nov 2022
- First submitted
- 9 Nov 2022
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No personal data will be made available publicly or to other researchers.
Publications
Amann M, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans. J Physiol. 2009 Jan 15;587(1):271-83. doi: 10.1113/jphysiol.2008.163303. Epub 2008 Nov 17.
PubMed 19015193Wan HY, Weavil JC, Thurston TS, Georgescu VP, Bledsoe AD, Jessop JE, Buys MJ, Richardson RS, Amann M. The muscle reflex and chemoreflex interaction: ventilatory implications for the exercising human. J Appl Physiol (1985). 2020 Oct 1;129(4):691-700. doi: 10.1152/japplphysiol.00449.2020. Epub 2020 Aug 20.
PubMed 32816637
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Muscle Reflex Inhibition on Cardiorespiratory Responses to Exercise in Hypoxia
- ClinicalTrials.gov ID
- NCT05619887
- Acronym / sponsor ID
- Muscle_reflex_hypoxia
- Conditions
- Dyspnea, Muscle Strain
- Keywords
- Dyspnea, Exercise, Muscle reflex, Type III/IV afferents
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Jun 2023 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 17 Nov 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.
The goal of this interventional study is to compare muscle reflex function under settings of normoxia (normal oxygen level), acute hypoxia (brief oxygen-lack) and chronic hypoxia (long-duration exposure to oxygen-lack).
The main question is: Does the muscle reflex adapt to chronic hypoxia?
Young, healthy participants will complete light-to-high intensity cycling exercise with and without suppression of the muscle reflex. Suppression of the muscle reflex will be via spinal administration of the opioid Fentanyl. In the control condition, saline will be administered into the spinal space. Participants will complete control (saline) and experimental (Fentanyl) exercise conditions at sea-level (Kelowna, BC, Canada) breathing room air and whilst breathing a lower fraction of oxygen (acute hypoxia). Thereafter, participants will complete the exercise test after living at high altitude (White Mountain, CA, USA) for 2 weeks whilst breathing room air (chronic hypoxia) and breathing a higher fraction of oxygen (restored normoxia).
Detailed description
Purpose:
To determine whether muscle reflex control of cardiorespiratory function is sensitized by chronic exposure to low oxygen environments. To do this, fentanyl will be administered into the lumbar spine to suppress nerve activity coming from the muscle during upright cycling exercise.
Hypothesis:
Cardiorespiratory responses (ventilation, blood pressure and heart rate) to cycling exercise will be suppressed when muscle reflex activity is partially blocked with fentanyl administration. This suppression will be augmented in a dose-dependent manner with the duration of hypoxic exposure.
Design:
This is a repeated measures cross-over design with participants completing control (saline) and experimental (fentanyl) conditions both low and high altitude; a total of six visits is required. Sea level testing sessions will involve a cycling exercise bout while breathing room air and a second exercise bout breathing a hypoxic gas mixture meant to simulate the altitude at White Mountain. High altitude testing sessions will involve the same cycling exercise bout while breathing room air and another exercise bout while breathing a hyperoxic gas mixture meant to simulate the altitude in Kelowna. Cardiorespiratory (ventilation, blood pressure and heart rate) will be measured throughout with (fentanyl) and without (saline) muscle reflex suppression. A 7-km time trial test will be performed during each visit to determine how the muscle reflex influences exercise performance.
Experimental procedures:
Participants will visit the lab on six occasions; 3 in both Kelowna and White Mountain. Participants will be requested to practice regular exercise and dietary habits that can be easily replicated in the 24 hours prior to every laboratory visit. Exercise and dietary patterns will be documented during the first visit and thereafter the participants will be reminded of these practices and instructed to match them as closely as possible in the 24 hours leading up to all subsequent visits. Participants will only be instructed to avoid heavy exercise in the 12 hours prior to testing sessions. On the first visit (Kelowna), participants will be introduced into the lab, where we will give oral and written instruction detailing the procedures and associated risks related to participating. Details of the experimental visits are outlined below:
Sea level:
- Familiarization and fitness test (1 h) General introduction to the lab, testing equipment and measurements devices. Maximal aerobic power test on an upright cycle ergometer.
- Main experimental visit #1, saline or fentanyl (2 h) Invasive cannulas will be inserted and drugs administered by an anesthetist. Complete four steady-state exercise bouts (3 min each) while breathing room air.
After a 2 min wash-in, complete four steady-state exercise bouts (3 min each) while breathing hypoxic gas (FiO2 = 0.15).
Complete a 7 km time trial test. - Main Experimental visit #2, Intrathecal (spinal) saline or fentanyl (2 h) Complete identical procedures as experimental visit #1, but the opposite condition.
High altitude:
- High altitude fitness test #1 (30 min) Maximal aerobic power test on upright cycle ergometer.
- Main experimental visit #3, saline or fentanyl (2 h) Invasive cannulas will be inserted and drugs administered by an anesthetist. Complete four steady-state exercise bouts (3 min each) while breathing room air.
After a 2 min wash-in, complete four steady-state exercise bouts (3 min each) while breathing hyperoxic gas (FiO2 = 0.30).
Complete a 7 km time trial test.
- Main experimental visit #4, saline or fentanyl (2 h) Complete identical procedures as experimental visit #3, but the opposite condition.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- Participants will complete all interventions (control and experimental) following drug washout.
| Arm | Type | Receives |
|---|---|---|
| Sea level control | Placebo comparator | Other: SalineSea level exercise will be completed after the administration of 1 mL of isotonic saline into the intrathecal (spinal) space between L3-L4. |
| Sea level experimental (muscle reflex suppression) | Experimental | Drug: FentanylSea level exercise will be completed after the administration of 0.25 mL of fentanyl into the intrathecal (spinal) space between L3-L4. |
| High altitude control | Placebo comparator | Other: SalineHigh altitude exercise will be completed after the administration of 1 mL of isotonic saline into the intrathecal (spinal) space between L3-L4. |
| High altitude experimental (muscle reflex suppression) | Experimental | Drug: FentanylHigh altitude exercise will be completed after the administration of 0.25 mL of fentanyl into the intrathecal (spinal) space between L3-L4. |
Who may qualify
- Ages
- 19 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- aged 19 - 40 years old
- not taking medications (exception oral contraception)
- no history of cardiovascular, respiratory or neurological disease
- members of the high altitude expedition to White Mountain in 2023
Key exclusion criteria (5 listed)
- post-menopausal or pregnant
- obese
- current smokers
- taking prescription medications that may affect responses to exercise
- All potential participants will be screened by a physician to identify co-morbidities
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 |
|---|---|---|
| FentanylAlso: fentaNYL CitrateFentanyl, when administered into the intrathecal (spinal) space suppresses feedback from the muscles below the site of action, i.e., the legs. It does not affect resting cardiorespiratory responses. We are using this to test what role the muscle reflex plays during exercise. | Drug | High altitude experimental (muscle reflex suppression), Sea level experimental (muscle reflex suppression) |
| SalineAn equal volume (as above) of saline will be administered into the intrathecal (spinal) space. This has no effect of cardiorespiratory responses at rest or during exercise; it is to control for the invasiveness of the procedure required to suppress muscle feedback in the experimental condition. | Other | High altitude control, Sea level control |
Primary outcome
Ventilation
Time frame: Data collected during steady-state breathing in the last minute of exercise
Ventilation, in liters per minute.
1 secondary outcome
Mean arterial blood pressure (entire pressure wave)
Time frame: Data collected during steady-state breathing in the last minute of exercise
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2022.
- Results publication: PubMed 19015193Amann M, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Opioid-mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans. J Physiol. 2009 Jan 15;587(1):271-83. doi: 10.1113/jphysiol.2008.163303. Epub 2008 Nov 17.
- Results publication: PubMed 32816637Wan HY, Weavil JC, Thurston TS, Georgescu VP, Bledsoe AD, Jessop JE, Buys MJ, Richardson RS, Amann M. The muscle reflex and chemoreflex interaction: ventilatory implications for the exercising human. J Appl Physiol (1985). 2020 Oct 1;129(4):691-700. doi: 10.1152/japplphysiol.00449.2020. Epub 2020 Aug 20.
- Individual participant dataSharing planned: No. No personal data will be made available publicly or to other researchers.
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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.
Philip N Ainslie, PhD principal investigator
University of British Columbia- Okanagan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fentanyl and Saline in people with Dyspnea and Muscle Strain, run by University of British Columbia at 1 site 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 4 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 23 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Travis D Gibbons, PhD (778.583.6976, travis.gibbons@ubc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilation (time frame: Data collected during steady-state breathing in the last minute of exercise). 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 NCT05619887, which also lists 2 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 23 Nov 2022.