Recruiting

AIH Protocols

Sponsor:

University of Florida

Code:

NCT07002437

Conditions

Spinal Cord Injuries (SCI)

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Augmented Acute Intermittent Hypoxia (aAIH)

Acute Intermittent Hypercapnic-Hypoxia (AIHH)

Sham AIH

Study Details

Brief summary:

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 (2 weeks to 6 months post injury), is to preliminarily compare the 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. Our 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, we are also 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 ID

NCT07002437

Start date

Nov 20, 2025

Status verified date

Nov, 2025

Completion date

Jul, 2027

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Adults 18-70 years of age
2. Sub-acute incomplete SCI 2 weeks 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.

-OR- Sub-acute complete SCI 2 weeks to 6 months after injury at or below C4-T6 Complete SCI based on the absence of residual sensory or motor function below the level of injury or injury classification of A 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

Exclusion Criteria:

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 hospital

Study Design

Enrollment

18 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

sham comparator: Sham

Participants will complete a baseline testing session, 6 sessions of sham intervention (5, 3-minute episodes of 21% O2, 2-minute intervals), and post-test assessments 1-day and 1-week after the last intervention.

experimental: AIHH

Participants will complete a baseline testing session, 6 sessions of acute intermittent hypercapnic hypoxia (AIHH) intervention (15, 1-minute episodes of 9-13% O2 + 4-5% CO2, 1.5-minute intervals), and post-test assessments 1-day and 1-week after the last intervention.

experimental: aAIH

Participants will complete a baseline testing session, 6 sessions of augmented acute intermittent hypoxia (aAIH) intervention (3, 5-minute episodes of 9-13% O2, 3-minute intervals), and post-test assessments 1-day and 1-week after the last intervention.

Interventions

Augmented Acute Intermittent Hypoxia (aAIH)

aAIH (augmented acute intermittent hypoxia) consists of 3, 5-minute episodes of low oxygen (9-13% O2), interspersed with 3-min room air intervals.

Each study participant will complete 6 sessions of augmented AIH (aAIH), which consists of 3, 5-minute exposures. Each exposure involves a 5-minute hypoxic episode (9-13% inspired O2), with a 3-min interval of room air breathing (21% O2). Gas mixtures will be delivered via Douglas bags (pre-filled with desired gas mixture) that are coupled to a non-rebreathing valve and facemask. A manual-control valve allows seamless gas mixture switching. Participant safety will be continuously monitored in real-time using non-invasive sensors and LabChart software. For instance, inspired and expired concentrations of O2 will be monitored by continuous recordings of arterial O2 saturation and end-tidal gas, respectively. Furthermore, vital signs (respiratory rate, tidal volume, heart rate, and blood pressure) will be continuously monitored.

Acute Intermittent Hypercapnic-Hypoxia (AIHH)

AIHH consists of 1-min episodes of low oxygen (9% O2) and elevated carbon dioxide (5% CO2), interspersed with 1.5 min room air.

Each participant will complete 6 sessions of AIHH exposure, which consists of 15, 1-minute hypercapnic hypoxic episodes (4-5% inspired CO2, 9-13% inspired O2), with 1.5-minute intervals of room air breathing (21% O2). Gas mixtures will be delivered in the same manner described for AIH intervention. Participant safety will be continuously monitored in real-time using LabChart software. For instance, inspired and expired concentrations of CO2 and O2 will be monitored by continuous recordings of arterial O2 saturation and end-tidal gas, respectively. Furthermore, vital signs (respiratory rate, heart rate, and blood pressure) will be monitored.

Sham AIH

Six sessions of sham AIH with episodes of normal room air (21% O2).

Sham experiments will use methods identical to AIH/AIHH protocols except that normoxic gas (21% inspired O2) will be delivered. Since the timing and intervals vary with each protocol, the sham will use a distinct protocol involving 5, 3-min episodes with 2 min intervals between each episode. The valve on the non-rebreathing mask will be turned to deliver these episodes, but 21% O2 will be delivered throughout.

Primary outcome measure

  • Change in Maximal Inspiratory Pressure [ Time Frame: Baseline, 1-day, and 1-week following intervention ]
  • Change in Maximal Expiratory Pressure [ Time Frame: Baseline, 1-day, and 1-week following intervention ]
  • Change in Cough Function [ Time Frame: Baseline, 1-day, and 1-week following intervention ]

Central Contacts and Locations

Central contacts

Emily J Fox, PT, DPT, MHS, PhD

904-742-2500ejfox@phhp.ufl.edu

Hannah J Snyder, M.S.

904-345-6910Hannah.Snyder@brooksrehab.org

Locations

Brooks Rehabilitation

Recruiting

Jacksonville, Florida, United States, 32216

Contacts

Hannah J Snyder

904-345-6910Hannah.Snyder@brooksrehab.org

Principal Investigator:

Emily J Fox, PT, DPT, MHS, PhD

More Information

Sponsor

University of Florida

Last update posted

Dec 3, 2025

Last verified

Nov, 2025

Keywords

  • Spinal Cord Injury
  • Intermittent Hypoxia
  • breathing
  • subacute
  • respiratory
  • acute intermittent hypoxia
  • hypoxia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Florida on 2025-12-03.