Back to resultsAIH-induced Walking Recovery After Subacute SCI
Primary Purpose
Spinal Cord Injury
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Daily acute intermittent hypoxia (dAIH)
dSHAM
Walking
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Cord Injury focused on measuring walk, rehabilitation, strength, movement, spinal cord trauma, spinal cord injury
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)
Sites / Locations
- Shepherd Center
- Spaulding Rehabilitation Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Sham Comparator
Experimental
Sham Comparator
Other
Arm Label
Non-ambulatory - dAIH
Non-ambulatory - dSHAM
Ambulatory - dAIH+Walk
Ambulatory - dSHAM+Walk
Ambulatory-Walk
Arm Description
Non-ambulatory subjects will be randomly assigned to receive 10 sessions of daily acute intermittent hypoxia (dAIH) 10 treatment visits at a frequency of 5 days each week for 2 weeks.
Non-ambulatory subjects will be randomly assigned to receive 10 sessions of daily room air (dSHAM) 10 treatment visits at a frequency of 5 days each week for 2 weeks.
Ambulatory subjects will be randomly assigned to receive 10 sessions of daily acute intermittent hypoxia (dAIH) coupled with 60 minutes of walking practice at a frequency of 5 days each week for 2 weeks.
Ambulatory subjects will be randomly assigned to receive 10 sessions of daily room air (dSHAM) coupled with 60 minutes of walking practice at a frequency of 5 days each week for 2 weeks.
Ambulatory subjects will be randomly assigned to 10 sessions of walking practice only for 5 consecutive sessions/week x 2 weeks.
Outcomes
Primary Outcome Measures
Change in walking recovery, assessed by timed up-and-go (TUG) test
The TUG test is used to assess the dynamic balance of an individual. It measures the amount of time (recorded in seconds) it takes for the individual to rise from a standard arm chair, walk a distance of 3 meters and return to the initial position resting against the back of the chair. Participants will perform up to three trials of the TUG test. Average speed across TUG trials will be used for analysis. Change is the difference between the end of session 10 and baseline.
Change in walking recovery, assessed by 6 minute walk test (6MWT)
Participants perform the 6MWT at their fastest, most comfortable walking speed sustainable for 6 minutes. Distances will be recorded at 2 and 6 minutes. The test will be based upon the participant's ability to finish each assessment without human assistance. Change is the difference between the end of session 10 and baseline.
Change in walking recovery, assessed by 10 meter walk test (10MWT)
Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Change is the difference between the end of session 10 and baseline.
Secondary Outcome Measures
Change in pain severity
Participants will report their pain level using the Wong-Baker FACES scale. The scale is from 0 to 5; 0 being no pain and 5 being extreme pain. Change is the difference between the end of session 10 and baseline.
Change in spasticity
Spasticity will be assessed using the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS). The study team will quantify the total lower extremity spasticity score using the cumulative sum of 3 SCATS subscales: clonus (0=no spasticity; 3=severe), flexor (0=no spasticity; 3=severe), and extensor (0=no spasticity; 3=severe). Change is the difference between the end of session 10 and baseline.
Systemic hypertension incidence rate
Participants will have their systolic and diastolic blood pressure measured. A systemic hypertensive event is quantified as a systolic pressure exceeding 140mmHg and/or diastolic pressure exceeding 90mmHg. A hypertension incident rate is the number of hypertensive events divided by the total person-time. Person-time is in units of person-measures (the sum of the total number of BP measurements) taken for each person. Person-measures accounts for the total number of chances for detecting a hypertensive event and accounts for measurements not made due to drop-out or a disqualifying adverse event
Autonomic dysreflexia incidence rate
The occurrence of autonomic dysreflexia will be assessed. An autonomic dysreflexia event will constitute a participant having a systolic blood pressure (SBP) increase from baseline of 20mmHg or SBP greater than 150mmHg with complaints of headache, diaphoresis, and/or blurred vision and will be diagnosed by the study team clinicians.
Full Information
NCT ID
NCT02632422
First Posted
December 14, 2015
Last Updated
February 6, 2023
Sponsor
Spaulding Rehabilitation Hospital
Collaborators
United States Department of Defense
1. Study Identification
Unique Protocol Identification Number
NCT02632422
Brief Title
AIH-induced Walking Recovery After Subacute SCI
Official Title
Intermittent Hypoxia-Induced Recovery of Overground Walking in Persons With Subacute SCI
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2015 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Spaulding Rehabilitation Hospital
Collaborators
United States Department of Defense
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury
Keywords
walk, rehabilitation, strength, movement, spinal cord trauma, spinal cord injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
125 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Non-ambulatory - dAIH
Arm Type
Experimental
Arm Description
Non-ambulatory subjects will be randomly assigned to receive 10 sessions of daily acute intermittent hypoxia (dAIH) 10 treatment visits at a frequency of 5 days each week for 2 weeks.
Arm Title
Non-ambulatory - dSHAM
Arm Type
Sham Comparator
Arm Description
Non-ambulatory subjects will be randomly assigned to receive 10 sessions of daily room air (dSHAM) 10 treatment visits at a frequency of 5 days each week for 2 weeks.
Arm Title
Ambulatory - dAIH+Walk
Arm Type
Experimental
Arm Description
Ambulatory subjects will be randomly assigned to receive 10 sessions of daily acute intermittent hypoxia (dAIH) coupled with 60 minutes of walking practice at a frequency of 5 days each week for 2 weeks.
Arm Title
Ambulatory - dSHAM+Walk
Arm Type
Sham Comparator
Arm Description
Ambulatory subjects will be randomly assigned to receive 10 sessions of daily room air (dSHAM) coupled with 60 minutes of walking practice at a frequency of 5 days each week for 2 weeks.
Arm Title
Ambulatory-Walk
Arm Type
Other
Arm Description
Ambulatory subjects will be randomly assigned to 10 sessions of walking practice only for 5 consecutive sessions/week x 2 weeks.
Intervention Type
Other
Intervention Name(s)
Daily acute intermittent hypoxia (dAIH)
Intervention Description
Each participant will be exposed to 10 sessions of daily acute intermittent hypoxia (dAIH) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes which include intervals of 1.5 minute hypoxia (FIO2=0.10±0.02, i.e. 10% O2) and 1 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily acute intermittent hypoxia (dAIH).
Intervention Type
Other
Intervention Name(s)
dSHAM
Intervention Description
Each participant will be exposed to 10 sessions of daily room air (dSHAM) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes of 1.5 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily room air (dSHAM).
Intervention Type
Other
Intervention Name(s)
Walking
Intervention Description
Participants will participate in 10 days of walking practice sessions. Walking practice sessions will immediately follow (within 60 minutes) the breathing intervention during training visits and will last for 60 minutes.
Walking practice will incorporate 5 walking-related tasks:
walking balance (e.g., walking with turns)
skilled walking tasks (e.g., negotiating obstacles)
walking with secondary task (e.g., walking and talking)
endurance
speed
Primary Outcome Measure Information:
Title
Change in walking recovery, assessed by timed up-and-go (TUG) test
Description
The TUG test is used to assess the dynamic balance of an individual. It measures the amount of time (recorded in seconds) it takes for the individual to rise from a standard arm chair, walk a distance of 3 meters and return to the initial position resting against the back of the chair. Participants will perform up to three trials of the TUG test. Average speed across TUG trials will be used for analysis. Change is the difference between the end of session 10 and baseline.
Time Frame
Baseline, Post-session 10 (up to two weeks)
Title
Change in walking recovery, assessed by 6 minute walk test (6MWT)
Description
Participants perform the 6MWT at their fastest, most comfortable walking speed sustainable for 6 minutes. Distances will be recorded at 2 and 6 minutes. The test will be based upon the participant's ability to finish each assessment without human assistance. Change is the difference between the end of session 10 and baseline.
Time Frame
Baseline, Post-session 10 (up to two weeks)
Title
Change in walking recovery, assessed by 10 meter walk test (10MWT)
Description
Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Change is the difference between the end of session 10 and baseline.
Time Frame
Baseline, Post-session 10 (up to two weeks)
Secondary Outcome Measure Information:
Title
Change in pain severity
Description
Participants will report their pain level using the Wong-Baker FACES scale. The scale is from 0 to 5; 0 being no pain and 5 being extreme pain. Change is the difference between the end of session 10 and baseline.
Time Frame
Baseline, Post-session 10 (up to two weeks)
Title
Change in spasticity
Description
Spasticity will be assessed using the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS). The study team will quantify the total lower extremity spasticity score using the cumulative sum of 3 SCATS subscales: clonus (0=no spasticity; 3=severe), flexor (0=no spasticity; 3=severe), and extensor (0=no spasticity; 3=severe). Change is the difference between the end of session 10 and baseline.
Time Frame
Baseline, Post-session 10 (up to two weeks)
Title
Systemic hypertension incidence rate
Description
Participants will have their systolic and diastolic blood pressure measured. A systemic hypertensive event is quantified as a systolic pressure exceeding 140mmHg and/or diastolic pressure exceeding 90mmHg. A hypertension incident rate is the number of hypertensive events divided by the total person-time. Person-time is in units of person-measures (the sum of the total number of BP measurements) taken for each person. Person-measures accounts for the total number of chances for detecting a hypertensive event and accounts for measurements not made due to drop-out or a disqualifying adverse event
Time Frame
Post-session 10 (up to two weeks)
Title
Autonomic dysreflexia incidence rate
Description
The occurrence of autonomic dysreflexia will be assessed. An autonomic dysreflexia event will constitute a participant having a systolic blood pressure (SBP) increase from baseline of 20mmHg or SBP greater than 150mmHg with complaints of headache, diaphoresis, and/or blurred vision and will be diagnosed by the study team clinicians.
Time Frame
Post-session 10 (up to two weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Randy Trumbower, PT, PhD
Organizational Affiliation
Harvard Medical School (HMS and HSDM)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shepherd Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Spaulding Rehabilitation Hospital
City
Cambridge
State/Province
Massachusetts
ZIP/Postal Code
02138
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
28972191
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.
Results Reference
background
PubMed Identifier
24285617
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.
Results Reference
background
PubMed Identifier
21821826
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.
Results Reference
background
PubMed Identifier
24618214
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.
Results Reference
background
PubMed Identifier
28762876
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.
Results Reference
background
PubMed Identifier
29648987
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.
Results Reference
background
PubMed Identifier
32641012
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.
Results Reference
background
PubMed Identifier
32682613
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.
Results Reference
result
Links:
URL
http://inspire-lab.org
Description
INSPIRE Lab - mission is to inspire persons with paralysis to move again
Available IPD and Supporting Information:
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.inspire-lab.org/contact-us
Available IPD/Information Comments
Requests for study informed consent may be made using the lab's contact form.
Learn more about this trial
AIH-induced Walking Recovery After Subacute SCI
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