BioFLO for Respiratory Recovery in SCI

Genetic Biomarkers of Intermittent Hypoxia-Induced Respiratory Motor Plasticity in Chronic SCI

Acute intermittent hypoxia (AIH) involves brief (1 min), repeated episodes (~15) of breathing low oxygen air to stimulate spinal neuroplasticity. Animal and human studies show that AIH improves motor function after spinal cord injury, particularly with slightly increased carbon dioxide (hypercapnic AIH; AIHH) and task-specific training. Using a double blind cross-over design, the study will test whether AIHH improves breathing more than AIH and whether specific genetic variations are related to individuals' intervention responses.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Other: Acute Intermittent Hypoxia (AIH); Other: Acute Intermittent Hypercapnic-Hypoxia (AIHH); Other: Sham AIH

Detailed Description

This study will consist of two parts - single-session testing days, and respiratory strength training blocks. If a participant is not eligible to enroll in single-day testing, they will be asked to enroll in only the respiratory strength training blocks.

On single-session testing days, participants will be asked to come in on three separate days they will complete a battery of tests, then be given one of three interventions, and then complete the same battery of tests. The three interventions are acute intermittent hypoxia (AIH), acute intermittent hypercapnic-hypoxia (AIHH), or sham acute intermittent hypoxia (sham AIH). These interventions are explained in more detail below.

During respiratory strength training blocks, participants will receive five days of AIH, AIHH, or sham AIH in combination with respiratory strength training, which uses small hand-held devices to strengthen the muscles used for breathing. Participants will be asked to complete all three blocks to receive all three interventions. In addition to 5 days of interventions and respiratory strength training, the respiratory strength training blocks include testing 1 day, 3 days, and 7 days after the 5 days of respiratory strength training.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emily J Fox, PT, MHS, PhD; Phone Number: 904-742-2500; Email: ejfox@phhp.ufl.edu
• Study Contact Backup: Name: Hannah Snyder, M.S.; Phone Number: 904-345-6910; Email: Hannah.snyder@brooksrehab.org

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Recruiting
      • Brooks Rehabilitation
      • Contact: Emily J. Fox, MHS, DPT, PhD; Phone Number: (904) 742-2500; Email: ejfox@phhp.ufl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults 18-70 years of age

2. Chronic incomplete SCI ≥ 1 year at or below C1-T12

   • 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- Chronic complete SCI ≥1 year at or below C4-T12

   • 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
5. 20% impairment in maximal inspiratory, maximal expiratory pressure generation, or both relative to normative values

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 recurrent autonomic dysreflexia

Exclusion for involvement in TMS - History of seizure disorder, uncontrolled migraines, presence of cardiac pacemaker, metal implants in skull, medications that lower seizure threshold.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-session testing days; Participants will complete three separate single-session testing days. Baseline testing will be performed, then on each day, participants will receive AIH, AIHH, and sham AIH in random order. Post-testing will occur after each intervention.	Other: Acute Intermittent Hypoxia (AIH); AIH (acute intermittent hypoxia) consists of short episodes of low oxygen (9% O2).; Other: Acute Intermittent Hypercapnic-Hypoxia (AIHH); AIHH consists of short episodes of low oxygen (9% O2) and elevated carbon dioxide (4% CO2).; Other: Sham AIH; A single session of sham AIH with episodes of normal room air (21% O2).
Experimental: Respiratory strength training blocks; Participants will complete three separate respiratory strength training blocks. In each block, participants will receive 5 days of AIH, 5 days of AIHH, and 5 days of sham AIH in random order, followed by respiratory strength training. Each block will include 5 days of intervention and training, and post-testing 1, 3, and 7 days after intervention and training has concluded.	Other: Acute Intermittent Hypoxia (AIH); AIH (acute intermittent hypoxia) consists of short episodes of low oxygen (9% O2).; Other: Acute Intermittent Hypercapnic-Hypoxia (AIHH); AIHH consists of short episodes of low oxygen (9% O2) and elevated carbon dioxide (4% CO2).; Other: Sham AIH; A single session of sham AIH with episodes of normal room air (21% O2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in motor evoked potential	The change in peak-to-peak amplitude of the motor evoked potential of the diaphragm will be tested using transcranial magnetic stimulation.	Baseline, and 45-60 minutes after intervention on AIH day, AIHH day, and Sham AIH day
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.	Baseline, 1 day, 3 days, and 7 days after intervention blocks (daily AIH + respiratory strength training, daily AIHH + respiratory strength training, daily sham AIH + respiratory strength training.)
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.	Baseline, 1 day, 3 days, and 7 days after intervention blocks (daily AIH + respiratory strength training, daily AIHH + respiratory strength training, daily sham AIH + respiratory strength training.)

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: U.S. Army Medical Research Acquisition Activity
• Investigators: Principal Investigator: Emily Fox, DPT, MHS, PhD, University of Florida & Brooks Rehabilitation

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Estimated): November 5, 2025
• Last Update Submitted That Met QC Criteria: November 3, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: breathing; spinal cord injury; acute intermittent hypoxia; motor function
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Trauma, Nervous System; Spinal Cord Diseases; Pathological Conditions, Signs and Symptoms; Respiratory Aspiration; Spinal Cord Injuries
• Other Study ID Numbers: IRB202202891; W81XWH2210478 (Other Grant/Funding Number: US ARMY MED RES ACQUISITION)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No