Clinical trial NCT02632422: AIH-induced Walking Recovery After Subacute SCI
Official title: Intermittent Hypoxia-Induced Recovery of Overground Walking in Persons With Subacute SCI
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Spinal Cord Injury
Keywords: walk
rehabilitation
strength
movement
spinal cord trauma
spinal cord injury
Lead sponsor: Spaulding Rehabilitation Hospital
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2015-12-16
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine how mild breathing bouts of low oxygen may restore walking and leg strength in persons who have sustained a spinal cord injury.

Detailed description: The goal of the study is to determine whether repeatedly breathing mild bouts of low oxygen for brief periods (termed acute intermittent hypoxia (AIH)) improves recovery of walking and strength after spinal cord injury. This idea stems from animal studies on respiration, in which investigators showed that mild AIH improves breathing in rats with spinal injuries. These studies showed that AIH induces plasticity, strengthening neural connections by increasing the production of key proteins and improving the sensitivity of spinal cord circuitry. The ultimate goal of this research is to assess the potential of mild AIH as a therapeutic approach not only in persons with chronic spinal cord injury but also in persons with subacute injury. By applying AIH during early stages of recovery, the investigators hope to expand the potential benefits of AIH to a broader range of persons with spinal injury, thereby improving functional independence and quality of life for servicemen and civilians.

Eligibility criteria: Inclusion Criteria:

* 18 to 70 years old
* medically stable with medical clearance from physician to participate
* spinal cord injury (SCI) at or below C3 (phrenic sparing) and above L5 with at least motor function preserved below the neurologic level
* non-progressive etiology of spinal injury
* American Spinal Injury Association Impairment Scale (AIS) grade A-D
* 2-12 months post-injury (subacute)

Exclusion Criteria:

* severe concurrent illness or pain, including unhealed decubiti, severe neuropathic or chronic pain syndrome, infection (e.g. bladder), hypertension, cardiovascular disease, pulmonary disease, severe osteoporosis (history of fractures), active heterotopic ossification in the lower extremities, or history of peripheral nerve injury in the legs
* score less than 24 on Mini-Mental Exam
* severe autonomic dysreflexia
* history of cardiovascular/pulmonary complications
* pregnancy
* severe obstructive sleep apnea (OSA), characterized by uncontrolled hypoxia and sleep fractionation

Specific inclusion/exclusion criteria for recruiting non-ambulatory subjects:

Participation in this group requires all of the above inclusion/exclusion criteria, as well as being unable to complete any of the below measures:

* timed up-and-go (TUG) test
* 10-meter walk test (10MWT)
* 6-minute walk test (6MWT)

Specific inclusion/exclusion criteria for recruiting ambulatory subjects:

Participation in this group requires all of the above criteria, as well as successful completion of at least one below measure:

* timed up-and-go (TUG) test
* 10-meter walk test (10MWT)
* 6-minute walk test (6MWT)

Primary outcomes:
measure: Change in walking recovery, assessed by timed up-and-go (TUG) test
timeFrame: Baseline, Post-session 10 (up to two weeks)
measure: Change in walking recovery, assessed by 6 minute walk test (6MWT)
timeFrame: Baseline, Post-session 10 (up to two weeks)
measure: Change in walking recovery, assessed by 10 meter walk test (10MWT)
timeFrame: Baseline, Post-session 10 (up to two weeks)
Secondary outcomes:
measure: Change in pain severity
timeFrame: Baseline, Post-session 10 (up to two weeks)
measure: Change in spasticity
timeFrame: Baseline, Post-session 10 (up to two weeks)
measure: Systemic hypertension incidence rate
timeFrame: Post-session 10 (up to two weeks)
measure: Autonomic dysreflexia incidence rate
timeFrame: Post-session 10 (up to two weeks)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Shepherd Center
state: Georgia
city: Cambridge
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
Study officials:
affiliation: Harvard Medical School (HMS and HSDM)
name: Randy Trumbower, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Trumbower RD, Hayes HB, Mitchell GS, Wolf SL, Stahl VA. Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. Neurology. 2017 Oct 31;89(18):1904-1907. doi: 10.1212/WNL.0000000000004596. Epub 2017 Sep 29.
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: Hayes HB, Chvatal SA, French MA, Ting LH, Trumbower RD. Neuromuscular constraints on muscle coordination during overground walking in persons with chronic incomplete spinal cord injury. Clin Neurophysiol. 2014 Oct;125(10):2024-35. doi: 10.1016/j.clinph.2014.02.001. Epub 2014 Feb 14.
citation: Peters DM, Thibaudier Y, Deffeyes JE, Baer GT, Hayes HB, Trumbower RD. Constraints on Stance-Phase Force Production during Overground Walking in Persons with Chronic Incomplete Spinal Cord Injury. J Neurotrauma. 2018 Feb 1;35(3):467-477. doi: 10.1089/neu.2017.5146. Epub 2017 Oct 27.
citation: Sohn WJ, Tan AQ, Hayes HB, Pochiraju S, Deffeyes J, Trumbower RD. Variability of Leg Kinematics during Overground Walking in Persons with Chronic Incomplete Spinal Cord Injury. J Neurotrauma. 2018 Nov 1;35(21):2519-2529. doi: 10.1089/neu.2017.5538. Epub 2018 Jun 5.
citation: Naidu A, Peters DM, Tan AQ, Barth S, Crane A, Link A, Balakrishnan S, Hayes HB, Slocum C, Zafonte RD, Trumbower RD. Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol. BMC Neurol. 2020 Jul 8;20(1):273. doi: 10.1186/s12883-020-01851-9.
citation: Tan AQ, Papadopoulos JM, Corsten AN, Trumbower RD. An automated pressure-swing absorption system to administer low oxygen therapy for persons with spinal cord injury. Exp Neurol. 2020 Nov;333:113408. doi: 10.1016/j.expneurol.2020.113408. Epub 2020 Jul 17.