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Effects of Breathing Mild Bouts of Low Oxygen on Limb Mobility After Spinal Injury

Mechanisms of Intermittent Hypoxia-induced Motor Recovery in Persons With SCI

Status
Recruiting
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02323945
Enrollment
44
Registered
2014-12-24
Start date
2014-10-01
Completion date
2027-11-01
Last updated
2026-03-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Spinal Cord Injuries

Keywords

acute intermittent hypoxia, incomplete spinal cord injury, strength, walking, breathing

Brief summary

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 (SCI). The goal of the study is to understand the mechanisms by which intermittent hypoxia enhances motor function and spinal plasticity (ability of the nervous system to strengthen neural pathways based on new experiences) following SCI.

Detailed 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 questions remain. First, does intermittent hypoxia improve walking recovery by increasing strength or muscle coordination or both? Understanding its mechanisms will allow us to best apply intermittent hypoxia in the clinic. Second, initial studies indicate that the beneficial effects of intermittent hypoxia are greatest when intermittent hypoxia is used just prior to task training and that the benefits are greatest for the practiced task. The investigators will explore this possibility by examining the effects of intermittent hypoxia on walking ability and force production when applied alone and when applied in combination with walking training or strength training. The investigators expect to observe the greatest improvements in walking ability in those individuals receiving intermittent hypoxia with walking training and the greatest improvements in strength in response to intermittent hypoxia with strength training. Third, studies suggest that intermittent hypoxia induces spinal plasticity by increasing the expression of a key plasticity-promoting protein, brain-derived neurotrophic factor (BDNF). Mutations in the BDNF gene have been shown to impair BDNF functionality. Thus, the investigators will also explore the impact of BDNF polymorphisms on responsiveness to intermittent hypoxia therapy.

Interventions

OTHERAIH

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 on 5 consecutive days.

OTHERWalk

30 minutes of walking practice consisting of 5 repetitions of 6-minute walks

OTHERStrength

30 minutes of isometric ankle plantar flexion torque practice broken into 3 sets of 10 repetitions

Sponsors

Spaulding Rehabilitation Hospital
Lead SponsorOTHER
Foundation Wings For Life
CollaboratorOTHER
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
CollaboratorNIH

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes

Inclusion criteria

* Age 18 and 75 years (the latter to reduce likelihood of heart disease) * Medical clearance to participate * Lesion at or below C2 and above T12 with non-progressive etiology * Classified as motor-incomplete with visible volitional leg movement * Injury greater than 1 year

Exclusion criteria

* Concurrent severe medical illness (i.e., infection, cardiovascular disease, ossification, recurrent autonomic dysreflexia, unhealed decubiti, and history of pulmonary complications) * Pregnant women because of the unknown affects of AIH on pregnant women and fetus * History of seizures, brain injury, and/or epilepsy * Undergoing concurrent physical therapy * Diabetes * Cirrhosis * Caffeine and/or NSAID allergies or intolerances

Design outcomes

Primary

MeasureTime frameDescription
Change in overground walking enduranceBaseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)Endurance will be measured as the distance walked during 2 min and 6 min (6MWT).
Change in muscle strengthBaseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)Strength will be assessed as the maximum isometric torque produced by the ankle and measured by a 6 degrees-of-freedom (DOF) load cell.

Secondary

MeasureTime frameDescription
Change in overground walking speedBaseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)Speed will be assessed by the time required to walk 10 meters (10MWT).

Countries

United States

Contacts

CONTACTRandy D Trumbower, PT, PhD
randy.trumbower@mgh.harvard.edu617-952-6951
CONTACTStella Barth, BA
sbarth@partners.org617-952-6822
PRINCIPAL_INVESTIGATORRandy D Trumbower, PT, PhD

Harvard Medical School (HMS and HSDM)

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 21, 2026