Muscle Reflex Inhibition in Hypoxic Exercise

NCT05619887 | Unknown

• 1 other identifier: Muscle_reflex_hypoxia
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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). 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).

Conditions

Dyspnea; Muscle Strain

Keywords

Dyspnea; Exercise; Muscle reflex; Type III/IV afferents

Outcome Measures

Primary Outcomes (1)

• Ventilation

  Ventilation, in liters per minute.

  Data collected during steady-state breathing in the last minute of exercise

Secondary Outcomes (1)

• Mean arterial blood pressure (entire pressure wave)

  Data collected during steady-state breathing in the last minute of exercise

Other Outcomes (1)

• Exercise performance

  The duration, i.e., however long it takes to complete the exercise; this is typically 7-14 minutes

Study Arms (4)

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.

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.

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.

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.

Drug: Fentanyl

Interventions

Fentanyl DRUG

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.

Also known as: fentaNYL Citrate

High altitude experimental (muscle reflex suppression); Sea level experimental (muscle reflex suppression)

Saline OTHER

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.

High altitude control; Sea level control

Eligibility Criteria

• Age: 19 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia - Okanagan Campus

Kelowna, British Columbia, V1V1V7, Canada

Location

Related Publications (2)

• 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.

  PMID: 19015193 RESULT

• Wan 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.

  PMID: 32816637 RESULT

MeSH Terms

Conditions

Dyspnea; Sprains and Strains; Motor Activity

Interventions

Fentanyl; Sodium Chloride

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Behavior

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Philip N Ainslie, PhD

  University of British Columbia- Okanagan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Travis D Gibbons, PhD

CONTACT

778.583.6976; travis.gibbons@ubc.ca

Philip N Ainslie, PhD

CONTACT

250.807.8089; philip.ainlie@ubc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The participant will not know whether they are receiving placebo or fentanyl. The primary investigator will also no know if the participant is receiving placebo or fentanyl.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will complete all interventions (control and experimental) following drug washout.

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 17, 2022
• Study Start: June 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: June 1, 2024
• Last Updated: November 23, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)