Muscle Reflex Inhibition in Hypoxic Exercise

November 19, 2022 updated by: Phil Ainslie, University of British Columbia

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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1V1V7
        • University of British Columbia - Okanagan Campus
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Sea level control
Sea level exercise will be completed after the administration of 1 mL of isotonic saline into the intrathecal (spinal) space between L3-L4.
Other: Saline
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.
Experimental: Sea level experimental (muscle reflex suppression)
Sea level exercise will be completed after the administration of 0.25 mL of fentanyl into the intrathecal (spinal) space between L3-L4.
Drug: Fentanyl
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.
Other Names:
  • fentaNYL Citrate
Placebo Comparator: High altitude control
High altitude exercise will be completed after the administration of 1 mL of isotonic saline into the intrathecal (spinal) space between L3-L4.
Other: Saline
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.
Experimental: High altitude experimental (muscle reflex suppression)
High altitude exercise will be completed after the administration of 0.25 mL of fentanyl into the intrathecal (spinal) space between L3-L4.
Drug: Fentanyl
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.
Other Names:
  • fentaNYL Citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilation
Time Frame: Data collected during steady-state breathing in the last minute of exercise
Ventilation, in liters per minute.
Data collected during steady-state breathing in the last minute of exercise

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean arterial blood pressure (entire pressure wave)
Time Frame: Data collected during steady-state breathing in the last minute of exercise
Blood pressure, in millimeters of mercury
Data collected during steady-state breathing in the last minute of exercise

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exercise performance
Time Frame: The duration, i.e., however long it takes to complete the exercise; this is typically 7-14 minutes
Time, in seconds, to complete 7 kilometers of cycling, i.e. a time-trial
The duration, i.e., however long it takes to complete the exercise; this is typically 7-14 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Investigators

  • Principal Investigator: Philip N Ainslie, PhD, University of British Columbia- Okanagan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2023

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

November 9, 2022

First Submitted That Met QC Criteria

November 9, 2022

First Posted (Actual)

November 17, 2022

Study Record Updates

Last Update Posted (Actual)

November 23, 2022

Last Update Submitted That Met QC Criteria

November 19, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Muscle_reflex_hypoxia

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No personal data will be made available publicly or to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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