Clinical trial NCT03071393: Intermittent Hypoxia to Enhance Motor Function After Spinal Cord Injury
Official title: Acute Intermittent Hypoxia to Enhance Motor Function After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: acute intermittent hypoxia
breathing
spinal cord injury
motor function
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2017-03-06
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will examine if acute intermittent hypoxia (brief episodes of breathing lower oxygen), which has been shown to enhance plasticity and motor output, can enhance functional outcomes and muscle activation in individuals with spinal cord injury. Our aim is to assess breathing, sitting, standing and walking functional ability before and after acute intermittent hypoxia, compared to a sham treatment. This information may be useful in advancing rehabilitation for people with spinal cord injuries.

Detailed description: Recent evidence has shown that acute intermittent hypoxia can strengthen motor pathways after spinal cord injury, and enhance walking outcomes after walking rehabilitation compared to walking rehabilitation alone. A single session of acute intermittent hypoxia has also been shown to temporarily enhance breathing and limb strength in people with spinal cord injury. Further evidence supports the hypothesis that acute intermittent hypoxia acts on all motor pathways, and thus can enhance the strength of most muscles in the body.

Spinal cord injury affects the muscles that control respiration. Decreased respiratory muscle function can lead to diseases of the respiratory system, which are the primary cause of death and significant cause of re-hospitalization after spinal cord injury. Deficits in postural muscle function affect one's ability to balance, safely maintain a seated position, or ambulate after spinal cord injury, severely impacting daily activities such as self-care and feeding skills.

This study will test the hypothesis that a single session of acute intermittent hypoxia will increase strength and activation of the muscles that control respiration and posture, leading to improved scores on functional assessments in individuals with chronic spinal cord injury. Our long term goal is to better understand the therapeutic potential of acute intermittent hypoxia combined with physical rehabilitation for individuals with chronic spinal cord injury.

Eligibility criteria: Inclusion criteria:

1. Male or female, ages 18-65
2. Greater than 6 months post-spinal cord injury
3. Spinal cord injury affecting segments between C4-T12
4. No other known neurological disorders
5. Able to provide informed consent
6. no severe musculoskeletal impairments, open wounds, or skin lesions that would limit participation in functional assessments.

Exclusion criteria:

1. Presence of a self-reported uncontrolled medical condition including, but not limited to: cardiovascular disease; sleep apnea; obstructive lung disease; severe neuropathic or chronic pain; severe recurrent autonomic dysreflexia
2. Severe, untreated bladder or urinary tract infection
3. Presence of severe musculoskeletal impairments, open wounds, or skin lesions that would limit participation in functional assessments
4. Women who report being pregnant or test positive on a pregnancy test

Primary outcomes:
measure: Change in Maximal Inspiratory Pressure
timeFrame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
measure: Change in Maximal Expiratory Pressure
timeFrame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
measure: Change in Forced Vital Capacity
timeFrame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
measure: Change in Mouth Occlusion Pressure (P0.1)
timeFrame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Brooks Rehabilitation
state: Florida
Study officials:
affiliation: University of Florida
name: Emily J Fox, MHS, DPT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gonzalez-Rothi EJ, Lee KZ, Dale EA, Reier PJ, Mitchell GS, Fuller DD. Intermittent hypoxia and neurorehabilitation. J Appl Physiol (1985). 2015 Dec 15;119(12):1455-65. doi: 10.1152/japplphysiol.00235.2015. Epub 2015 May 21.
citation: Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27.
citation: Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5.
citation: Tester NJ, Fuller DD, Fromm JS, Spiess MR, Behrman AL, Mateika JH. Long-term facilitation of ventilation in humans with chronic spinal cord injury. Am J Respir Crit Care Med. 2014 Jan 1;189(1):57-65. doi: 10.1164/rccm.201305-0848OC.
citation: Satriotomo I, Nichols NL, Dale EA, Emery AT, Dahlberg JM, Mitchell GS. Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons. Neuroscience. 2016 May 13;322:479-88. doi: 10.1016/j.neuroscience.2016.02.060. Epub 2016 Mar 2.
citation: Sutor T, Cavka K, Vose AK, Welch JF, Davenport P, Fuller DD, Mitchell GS, Fox EJ. Single-session effects of acute intermittent hypoxia on breathing function after human spinal cord injury. Exp Neurol. 2021 Aug;342:113735. doi: 10.1016/j.expneurol.2021.113735. Epub 2021 May 2.