Acute Intermittent Hypoxia on Leg Function Following Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title:

Repetitive Exposure of Intermittent Hypoxia to Enhance Walking Recovery in Persons With Chronic Spinal Cord Injury

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02274116
• Other study ID #: 2017P001940c
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 2014
• Est. completion date: August 2024

Study information

• Verified date: November 2023
• 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 the nervous system controlling leg muscles is altered following spinal cord injury and how they may be affected by brief periods of low oxygen inhalation over time.

The investigators hypothesize:

• Acute intermittent hypoxia (AIH) exposure will increase maximum voluntary leg strength in persons with incomplete cervical spinal cord injury (SCI)

• AIH exposure will increase multijoint reflex excitability of leg muscles in persons with incomplete cervical SCI

• AIH exposure will increase walking performance in persons with incomplete cervical SCI

Description:

Accumulating evidence suggests that repeatedly breathing low oxygen levels for brief periods (termed intermittent hypoxia) is a safe and effective treatment strategy to promote meaningful functional recovery in persons with chronic spinal cord injury. Repetitive exposure to mild hypoxia triggers a cascade of events in the spinal cord, including new protein synthesis and increased sensitivity in the circuitry necessary for breathing and walking. Recently, the investigators demonstrated that daily (5 consecutive days) of intermittent hypoxia stimulated walking enhancement in persons with chronic spinal cord injury.

Despite these exciting findings, important clinical questions remain. For example, the investigators do not know if prolonged, but less intense intermittent hypoxia induces longer-lasting motor recovery as has been shown in rat models. The investigators hypothesize that repetitive exposures to modest bouts of low oxygen will enhance and prolong walking recovery in persons with chronic spinal cord injury. The investigators anticipate intermittent hypoxia-induced improvements in overground walking ability, likely due to greater balance in excitatory and inhibitory neural transmission. Whereas excitatory inputs drive walking, inhibitory inputs sculpt and coordinate muscle activity; yet so often remain compromised after chronic injury. Thus, the investigators also predict that repetitive exposures to intermittent hypoxia will result in improved inhibition and subsequently enhance muscle coordination during walking. The investigators will use multiple experimental approaches, including muscle electromyography, measurements of walking dynamics and stretch reflexes. Finally, it is critical to assure that repetitive exposures to intermittent hypoxia do not elicit pathologies characteristic of more severe, chronic hypoxia experienced by individuals with obstructive sleep apnea. The investigators will confirm that repetitive exposure to mild bouts of intermittent hypoxia is safe.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: August 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18 to 75 years old (the latter to reduce likelihood of heart disease);

• medically stable with clearance from physician to participate;

• motor---incomplete SCI at C2---L5 with non---progressive etiology;

• >6 months since SCI to ensure minimal confounds of spontaneous neurological recovery;

• those classified as ambulatory must have the ability to advance one step overground without human assistance.

Exclusion Criteria:

• concurrent illness, including unhealed decubiti, severe neuropathic or chronic pain syndrome, infection, cardiovascular disease, osteoporosis (history of fractures), active heterotopic ossification, or known history of peripheral nerve injury to legs;

• less than 24 on the Mini-mental Exam;

• recurrent autonomic dysreflexia

• cardiopulmonary complications

• concurrent physical therapy

• pregnancy because of unknown effects of AIH on a fetus, although women will not otherwise be excluded

Related Conditions & MeSH terms

• Hypoxia
• Spinal Cord Injuries
• Wounds and Injuries

Intervention

Other:
• SHAM - Intermittent Room Air - room air mixture
Participants will breathe intermittent room air via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.21±0.02 (normoxia). Participants will receive treatment 5 times per week for 2 weeks.
• AIH - Intermittent Hypoxia - hypoxia air mixture
Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.10±0.02 (hypoxia). Participants will receive treatment 5 times per week for 2 weeks.

Locations

Country	Name	City	State
United States	Spaulding Rehabilitation Hospital	Cambridge	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Spaulding Rehabilitation Hospital	Foundation Wings For Life

Country where clinical trial is conducted

United States, 

References & Publications (4)

Dale-Nagle EA, Hoffman MS, MacFarlane PM, Satriotomo I, Lovett-Barr MR, Vinit S, Mitchell GS. Spinal plasticity following intermittent hypoxia: implications for spinal injury. Ann N Y Acad Sci. 2010 Jun;1198:252-9. doi: 10.1111/j.1749-6632.2010.05499.x. — 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

Lovett-Barr MR, Satriotomo I, Muir GD, Wilkerson JE, Hoffman MS, Vinit S, Mitchell GS. Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. J Neurosci. 2012 Mar 14;32(11):3591-600. doi: 10.1523/JNEUROSCI.2908-11.2012. — 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 overground walking endurance	walking endurance (6 minute walk test - how far one can walk in 6 minutes)	Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks
Secondary	Change in overground walking speed	walking speed (10 meter walk test - how fast one can walk in 10 meters)	Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks