Hypoxia Pathways for Early Recovery After Spinal Cord Injury

Description

Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, diminishing breathing capacity and airway defense (e.g., cough). Indeed, respiratory impairment is a leading cause of infection, re-hospitalization and death after SCI. There is a critical need for new strategies to restore breathing ability and airway defense in people with SCI. Acute intermittent hypoxia (AIH) - repetitive exposure to brief episodes of low inspired oxygen - is a promising strategy to restore breathing capacity by promoting spinal neuroplasticity. Exciting outcomes in \>12 SCI trials completed to date demonstrate that AIH improves human respiratory and limb function. Unfortunately, \~40% of individuals exhibit minimal response to AIH, making it essential to 1) optimize AIH protocols to maximize functional benefits; and 2) identify genetic biomarkers distinguishing those most/least likely to benefit from AIH-based treatments. The purpose of the pilot study, to be conducted in a small sample of participants with sub-acute SCI (1 to 6 months post injury), is to preliminarily compare the immediate effects of two intermittent hypoxia protocols. Since AIH-induced plasticity may be induced via serotonin or adenosine-driven mechanisms and these pathways compete and inhibit each other, each protocol favors a distinct mechanistic pathway. The long-term objective is to test the hypothesis that a longer duration (i.e., augmented) hypoxia protocol, favoring adenosine mechanisms, enhances respiratory motor plasticity more than an AIH protocol targeting serotonin mechanisms (low O2 + CO2) in people with sub-acute SCI. Since an individual's genetics can influence the response to rehabilitation, investigators are also preliminarily investigating how certain genes are related to breathing changes after these treatments. Data acquired through this pilot study will be used to inform a larger, more definitive clinical trial and will contribute to estimations of the magnitude and direction of effects.

Conditions

Spinal Cord Injuries (SCI)

Study Overview

Study Details

Study overview

Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, diminishing breathing capacity and airway defense (e.g., cough). Indeed, respiratory impairment is a leading cause of infection, re-hospitalization and death after SCI. There is a critical need for new strategies to restore breathing ability and airway defense in people with SCI. Acute intermittent hypoxia (AIH) - repetitive exposure to brief episodes of low inspired oxygen - is a promising strategy to restore breathing capacity by promoting spinal neuroplasticity. Exciting outcomes in \>12 SCI trials completed to date demonstrate that AIH improves human respiratory and limb function. Unfortunately, \~40% of individuals exhibit minimal response to AIH, making it essential to 1) optimize AIH protocols to maximize functional benefits; and 2) identify genetic biomarkers distinguishing those most/least likely to benefit from AIH-based treatments. The purpose of the pilot study, to be conducted in a small sample of participants with sub-acute SCI (1 to 6 months post injury), is to preliminarily compare the immediate effects of two intermittent hypoxia protocols. Since AIH-induced plasticity may be induced via serotonin or adenosine-driven mechanisms and these pathways compete and inhibit each other, each protocol favors a distinct mechanistic pathway. The long-term objective is to test the hypothesis that a longer duration (i.e., augmented) hypoxia protocol, favoring adenosine mechanisms, enhances respiratory motor plasticity more than an AIH protocol targeting serotonin mechanisms (low O2 + CO2) in people with sub-acute SCI. Since an individual's genetics can influence the response to rehabilitation, investigators are also preliminarily investigating how certain genes are related to breathing changes after these treatments. Data acquired through this pilot study will be used to inform a larger, more definitive clinical trial and will contribute to estimations of the magnitude and direction of effects.

Intermittent Hypoxia-Induced Motor Plasticity in Sub-Acute Spinal Cord Injury

Hypoxia Pathways for Early Recovery After Spinal Cord Injury

Condition
Spinal Cord Injuries (SCI)
Intervention / Treatment

-

Contacts and Locations

Jacksonville

Brooks Rehabilitation Clinical Research Center, Jacksonville, Florida, United States, 32216

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. Adults 18-70 years of age
  • 2. Sub-acute incomplete SCI 1 to 6 months after injury, at or below C1-T6 Incomplete SCI based on residual sensory and motor function below the level of the injury or injury classification of B, C, D at initial screening according to the American Spinal Injury Association Impairment Classification and the International Standards for the Neurological Classification of SCI.
  • 3. Medically stable with physician clearance
  • 4. SCI due to non-progressive etiology
  • 1. Current diagnosis of an additional neurologic condition such as Multiple Sclerosis, Parkinson disease, stroke, or brain injury
  • 2. Severe illness or infection, including non-healing decubitus ulcers, untreated bladder or urinary tract infections, cardiovascular disease, lung disease, active heterotopic ossification, or uncontrolled hypertension
  • 3. Severe neuropathic pain
  • 4. Known pregnancy
  • 5. Severe uncontrolled autonomic dysreflexia
  • 6. Currently hospitalized in an acute care or inpatient rehabilitation hospital

Ages Eligible for Study

18 Years to 70 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Florida,

Emily J Fox, PT, DPT, MHS, PhD, PRINCIPAL_INVESTIGATOR, University of Florida & Brooks Rehabilitation

Study Record Dates

2026-12