Hypoxia Pathways for Spinal Cord Injury

(HyPER-FLO Trial)

Overseen By Hannah J Snyder, M.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Disqualifiers: Multiple sclerosis, Stroke, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to help people with spinal cord injuries improve breathing and airway defense. It tests two breathing treatments, Acute Intermittent Hypercapnic-Hypoxia (AIHH) and Augmented Acute Intermittent Hypoxia (aAIH), by exposing participants to low oxygen levels to determine which better enhances breathing ability. The trial also examines how genetics might influence a person's response to these treatments. Suitable candidates have had a spinal cord injury from 1 to 6 months ago and are medically stable. Participants will try each treatment on separate days to assess their response. As an unphased trial, this study offers participants the chance to contribute to pioneering research that could lead to new treatments for spinal cord injuries.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that treatments like those in this trial, which involve brief exposure to low oxygen levels, are generally well-tolerated. Research indicates these treatments can safely enhance nerve pathways in people with spinal cord injuries. Controlled exposure to low oxygen levels encourages recovery without significant risks.

This trial tests two specific treatments: acute intermittent hypercapnic-hypoxia (AIHH) and augmented acute intermittent hypoxia (aAIH). Promising data supports both. AIHH has increased blood pressure and nerve activity, potentially aiding recovery, and studies suggest it effectively and safely improves breathing. Similarly, aAIH shows potential for enhancing breathing and movement, with evidence indicating safety when used alone or with other therapies.

While no major safety concerns have been reported, about 40% of people may not respond strongly to these treatments. However, studies have not highlighted any significant adverse effects, suggesting these treatments are generally safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring Hypoxia Pathways for Spinal Cord Injury because these techniques could offer a fresh approach to treatment. Unlike standard treatments that often focus on surgery or medication to manage symptoms, Acute Intermittent Hypercapnic-Hypoxia (AIHH) and Augmented Acute Intermittent Hypoxia (aAIH) involve controlled exposure to low oxygen levels and carbon dioxide variations to potentially trigger pathways that boost recovery. This non-invasive method could promote neural plasticity, which is the ability of the brain and spinal cord to adapt and repair itself. If successful, these methods might provide quicker or more effective recovery options for spinal cord injury patients by tapping into the body's natural repair mechanisms.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

Research has shown that a treatment called acute intermittent hypoxia (AIH) can improve movement in people with spinal cord injuries by making the spinal cord more adaptable. Studies have found that AIH enhances breathing and limb movement in these individuals. However, about 40% of people might not experience significant improvement with AIH, highlighting the need to optimize its use.

This trial will test different versions of AIH, including augmented acute intermittent hypoxia (aAIH) and acute intermittent hypercapnic-hypoxia (AIHH). Early research suggests that aAIH might improve breathing control even more effectively than regular AIH. In one study, a single AIH session increased grip and pinch strength, with the best results observed about three hours after treatment. Both AIH and aAIH aim to improve breathing by encouraging changes in the spinal cord, but their effectiveness can vary among individuals. Participants in this trial will receive interventions in different sequences, including Sham, AIHH, and aAIH, to evaluate their effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Emily J Fox, PT, DPT, MHS, PhD

Principal Investigator

University of Florida & Brooks Rehabilitation

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with sub-acute incomplete or complete spinal cord injury (SCI) at or below C1-T6, occurring 1 to 6 months prior. Participants must be medically stable with physician clearance and have SCI from a non-progressive cause. Excluded are those with other neurological conditions, severe illness/infection, uncontrolled issues like hypertension, neuropathic pain, pregnancy, or current acute care hospitalization.

Inclusion Criteria

Medically stable with physician clearance

SCI due to non-progressive etiology

I am between 18 and 70 years old.

Exclusion Criteria

Known pregnancy

I have a neurologic condition like MS, Parkinson's, stroke, or brain injury.

I do not have severe illness or uncontrolled conditions like heart disease, lung disease, or high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Testing

Baseline testing will be performed before each intervention day

1 day

1 visit (in-person)

Intervention

Participants will receive interventions in the order of Sham, AIHH, and aAIH on separate days

3 days

3 visits (in-person)

Post-Intervention Testing

Post-testing will occur after each intervention to measure primary and secondary outcomes

1 hour after each intervention

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acute Intermittent Hypercapnic-Hypoxia (AIHH)
• Augmented Acute Intermittent Hypoxia (aAIH)
• Sham AIH

Trial Overview The study tests two hypoxia protocols on individuals with recent SCI: Augmented Acute Intermittent Hypoxia (aAIH), which may enhance respiratory function via adenosine mechanisms; and Acute Intermittent Hypercapnic-Hypoxia (AIHH), targeting serotonin pathways. A sham procedure serves as control. The goal is to determine the best approach for promoting respiratory motor plasticity and identify genetic markers predicting treatment response.

How Is the Trial Designed?

Group I: Sham, aAIH, AIHH Experimental Treatment 3 Interventions

Participants will complete three separate single-session testing days. Baseline testing will be performed, then on each day, participants will receive interventions in the following order: Sham, aAIH, and AIHH. Post-testing will occur after each intervention.

Group II: Sham, AIHH, aAIH Experimental Treatment 3 Interventions

Participants will complete three separate single-session testing days. Baseline testing will be performed, then on each day, participants will receive interventions in the following order: Sham, AIHH, and aAIH. Post-testing will occur after each intervention.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Brooks Rehabilitation

Collaborator

Trials

16

Recruited

1,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12232992/

Acute intermittent hypercapnic-hypoxia elicits central neural ... The results indicate that moderate AIHH elicits a central neural mechanism of respiratory motor plasticity and increases resting respiratory drive in awake ...

2. journals.physiology.org journals.physiology.org/doi/10.1152/physiol.2024.39.S1.1340

Combined therapeutic acute intermittent hypercapnic ... Unfortunately, tAIH effects on breathing function are less effective with chronic injury. On the other hand, tAIH restores non-respiratory (limb) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07002437

Hypoxia Pathways for Early Recovery After Spinal Cord Injury 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% ...

4. jefferson.edu jefferson.edu/academics/colleges-schools-institutes/rehabilitation-sciences/departments/outcomes-measurement/current-projects.html

Current Projects The outcomes from the current study establish the psychometric data to support the claim that assessing remotely is a valid and reliable way to measure physical ...

5. withpower.com withpower.com/trial/acute-intermittent-hypoxia-for-spinal-cord-injury-d78b4

Acute Intermittent Hypoxia for Spinal Cord Injury Research shows that Acute Intermittent Hypoxia (AIH) can improve motor function in individuals with chronic spinal cord injury by enhancing spinal plasticity, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12056581/

Cardiorespiratory Responses to Acute Intermittent Hypoxia in ... After spinal cord injury (SCI), cardiorespiratory control is impaired, threatening the regulation of arterial O2 and CO2 partial pressures and the transport of ...

7. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP288115

Acute intermittent hypercapnic hypoxia augments left ... Acute intermittent hypercapnic hypoxia (IHH) evokes persistent increases in vascular sympathetic activity and blood pressure.

8. reporter.nih.gov reporter.nih.gov/project-details/11218663

Project Details Identifying predictive biomarkers for acute intermittent hypoxia induced motor recovery in persons with incomplete spinal cord injury. 494, 1R03HD115657-01 ...