AIH-induced Walking Recovery After Subacute SCI

Spinal Cord Injury Clinical Trial

Official title:

Intermittent Hypoxia-Induced Recovery of Overground Walking in Persons With Subacute SCI

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02632422
• Other study ID #: 2017P001941
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 2015
• Est. completion date: December 30, 2024

Study information

• Verified date: May 2024
• Source: Spaulding Rehabilitation Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 125
• Est. completion date: December 30, 2024
• Est. primary completion date: July 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Other:
• Daily acute intermittent hypoxia (dAIH)
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).
• dSHAM
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).
• Walking
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

Locations

Country	Name	City	State
United States	Shepherd Center	Atlanta	Georgia
United States	Spaulding Rehabilitation Hospital	Cambridge	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Spaulding Rehabilitation Hospital	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Post-session 10 (up to two weeks)
Primary	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.	Baseline, Post-session 10 (up to two weeks)
Primary	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.	Baseline, Post-session 10 (up to two weeks)
Secondary	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.	Baseline, Post-session 10 (up to two weeks)
Secondary	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.	Baseline, Post-session 10 (up to two weeks)
Secondary	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	Post-session 10 (up to two weeks)
Secondary	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.	Post-session 10 (up to two weeks)

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