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

Mass General Brigham

Status: Enrolling

Conditions: Spinal Cord Injuries

Treatments: Other: Strength; Other: AIH; Other: Walk

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02323945

1R01HD081274-01 (U.S. NIH Grant/Contract)

2017P001940a

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups

AIH/Walk

Active Comparator group

Description:

Subjects with chronic, motor-incomplete SCI receive acute intermittent hypoxia (AIH) with walking practice, then AIH with strength practice and compare their efficacy on enhancing strength and/or walking performance.

Treatment:

Other: Walk

Other: AIH

AIH/Strength

Active Comparator group

Description:

Subjects with chronic, motor-incomplete SCI receive AIH with strength practice, then AIH with walking practice and compare their efficacy on enhancing strength and/or walking performance.

Treatment:

Other: AIH

Other: Strength