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Spinal Cord Injuries (SCI)HyPER-FLONCT07002437

Hypoxia Pathways for Early Recovery After Spinal Cord Injury

A study testing Augmented Acute Intermittent Hypoxia (aAIH) and Acute Intermittent Hypercapnic-Hypoxia (AIHH) in people with Spinal Cord Injuries (SCI), run by University of Florida at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Spinal Cord Injuries (SCI)
What is being tested?
Augmented Acute Intermittent Hypoxia (aAIH) and Acute Intermittent Hypercapnic-Hypoxia (AIHH)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
18 participants
Where
1 siteUnited States
Study dates
20 Nov 2025to Jul 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults 18-70 years of age
  • 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.
  • Medically stable with physician clearance
  • SCI due to non-progressive etiology

Who cannot join

  • Current diagnosis of an additional neurologic condition such as Multiple Sclerosis, Parkinson disease, stroke, or brain injury
  • 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
  • Severe neuropathic pain
  • Known pregnancy
  • Severe uncontrolled autonomic dysreflexia
  • Currently hospitalized in an acute care hospital

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Emily J Fox, PT, DPT, MHS, PhD contact

904-742-2500

ejfox@phhp.ufl.edu

Hannah J Snyder, M.S. contact

904-345-6910

Hannah.Snyder@brooksrehab.org

United States1 site, 1 recruiting
  • Brooks Rehabilitation

    Jacksonville, Florida, 32216

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

    Emily J Fox, PT, DPT, MHS, PhD

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

The specific focus of this pilot study is to obtain preliminary data to inform a larger, more definitive clinical trial. The long-term objective of this line of work is to test the hypothesis that an acute intermittent hypoxia protocol (3, 5 min episodes, 9-13% FiO2; augmented AIH (aAIH)) favoring adenosine mechanisms, enhances respiratory motor plasticity more than an AIH protocol targeting serotonin mechanisms (1 min 9% FiO2 + CO2) in people with sub-acute SCI. Since an individual's genetics can influence the response to rehabilitation, investigators are also collecting preliminary data regarding how certain genes are related to breathing changes after these treatments.

Data acquired through this pilot study will be used to estimate the magnitude and direction of effects.

This line of research will inform AIH protocol optimization to enhance the clinical effects of AIH treatments designed to improve rehabilitation outcomes.

The following Aims will be addressed:

Aim 1: To preliminarily test the hypothesis that augmented acute intermittent hypoxia (aAIH) is a more potent stimulus to induce respiratory motor plasticity than AIHH (low oxygen with hypercapnia) in people with sub-acute SCI.

The investigators predict that 6 sessions of aAIH (3, 5-minute episodes of 9-13% O2; 3-minute intervals) will elicit greater respiratory motor plasticity than AIHH (15, 1-minute episodes of 9-13% O2 with 4-5% CO2; 1.5-minute intervals) or Sham (5, 3-minute episodes of 21% O2) in individuals with SCI, 2 weeks to 6 months post injury.

The primary outcomes include maximum pressure generation and cough function 1-day and 1-week post-intervention. Secondary, exploratory outcomes will be biceps (elbow flexion) force output.

Aim 2: To obtain preliminary data regarding the association between dysfunctional genetic variants, linked with molecules necessary for AIH-induced respiratory motor plasticity, and the magnitude of response (change in primary outcomes) in response to aAIH or AIHH in individuals with sub-acute SCI.

The investigators predict that individuals with dysfunctional single nucleotide polymorphisms (SNPs) associated with pro-plasticity genes have blunted responses to aAIH and/or AIHH treatments.

  • Augmented Acute intermittent hypoxia (aAIH): This intervention will involve breathing low-oxygen air through a facemask that covers the nose and mouth. Participants will be asked to breathe the low-oxygen air for 3 periods (about 5 minutes each period). A mask will be secured and adjusted to the face and the participant will be able to breathe naturally and normally. Between the ~ 5 minute periods of lower oxygen, the participant will breathe higher oxygen levels that are 'normal' or consistent with room air for about 3 minutes. Heart rate, blood oxygen saturation, and blood pressure will be monitored. The gas mixture will be adjusted if a participant's blood oxygen saturation drops below 80%.
  • Acute intermittent hypercapnic hypoxia, lower oxygen with CO2 (AIHH): This intervention delivery using the facemask will be identical to the aAIH described above, except that lower oxygen will be combined with higher carbon dioxide air. For this intervention, the participant will be asked to breathe the low oxygen air with higher carbon dioxide air for 15 periods (~1 minute each). Between periods of breathing this gas mixture through the facemask, the participant will breathe higher oxygen levels that are normal for ~1.5 minutes. Heart rate, blood oxygen saturation, and blood pressure will be monitored. The gas mixture will be adjusted if a participant's blood oxygen saturation drops below 80%.
  • Sham/Placebo: This intervention will be identical to the two procedures described above, except that normal-oxygen, normal-carbon dioxide air (same as room air) will be delivered through the facemask for 5 periods (~3 minutes each). Heart rate, blood oxygen saturation, and blood pressure will be monitored.
Being tested
Augmented Acute Intermittent Hypoxia (aAIH), Acute Intermittent Hypercapnic-Hypoxia (AIHH), Sham AIH
Keywords
Spinal Cord Injury, Intermittent Hypoxia, breathing, subacute, respiratory, acute intermittent hypoxia, hypoxia
Medical subject headings
Spinal Cord Injuries, Respiratory Aspiration, Hypoxia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Augmented Acute Intermittent Hypoxia (aAIH)Other

    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)Other

    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 AIHOther

    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.

Study groups in NCT07002437
Study groupRoleWhat they receive
ShamSham comparatorParticipants 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.
Receives: Other: Sham AIH
AIHHExperimentalParticipants 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.
Receives: Other: Acute Intermittent Hypercapnic-Hypoxia (AIHH)
aAIHExperimentalParticipants 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.
Receives: Other: Augmented Acute Intermittent Hypoxia (aAIH)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Maximal Inspiratory Pressure

    Maximal inspiratory pressure is a non-invasive measure of the maximal force achieved when breathing in against an occluded airway.

    Measured: Baseline, 1-day, and 1-week following intervention

  2. Change in Maximal Expiratory Pressure

    Maximal expiratory pressure is a non-invasive measure of the maximal force achieved when breathing out against an occluded airway.

    Measured: Baseline, 1-day, and 1-week following intervention

  3. Change in Cough Function

    Cough function will be measured by non-invasive tests of cough volume acceleration during a maximal cough.

    Measured: Baseline, 1-day, and 1-week following intervention

Secondary outcomes (1)
  1. Change in Muscle Strength

    Change in muscle strength will be measured using a non-invasive force dynamometer.

    Measured: Baseline, 1-day, and 1-week following intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2025
  2. Study start20 Nov 2025
  3. Primary completionDec 2026 (estimated)
  4. Study completionJul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07002437
Sponsor's protocol ID
IRB202500467
Acronym
HyPER-FLO
Status last verified
Nov 2025
First submitted
2 May 2025
Last updated
3 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Augmented Acute Intermittent Hypoxia (aAIH) and Acute Intermittent Hypercapnic-Hypoxia (AIHH) in people with Spinal Cord Injuries (SCI), run by University of Florida at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Emily J Fox, PT, DPT, MHS, PhD (904-742-2500, ejfox@phhp.ufl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Maximal Inspiratory Pressure (time frame: Baseline, 1-day, and 1-week following intervention). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025.

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