FLO2 for Recovery After SCI

Acute Intermittent Hypoxia and Respiratory Strength Training to Improve Breathing Function After Spinal Cord Injury

Acute intermittent hypoxia (AIH) involves short (~1-2min) bouts of breathing low oxygen air to stimulate spinal neuroplasticity. Studies in rodents and humans indicate that AIH improves motor function after spinal cord injury (SCI). This study will use a double blind, cross-over design to test if the combination of AIH and respiratory strength training improves breathing function more than either approach alone in adults with chronic SCI.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injury (SCI)
• Intervention / Treatment: Other: Daily AIH Block; Other: Sham dAIH Block; Other: Respiratory Strength Training Block; Other: AIH + Strength Training Block

Detailed Description

Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, causing muscle paralysis and decreased breathing capacity. Since respiratory impairment is the major cause of illness and death with SCI, it is critical to devise new strategies to restore breathing function.

Repetitive exposure to brief episodes of low oxygen (acute intermittent hypoxia or AIH) has demonstrated to increase respiratory function in humans with chronic SCI. Additionally pre-clinical studies demonstrate that AIH-induced functional benefits are enhanced by combining AIH with task-specific training. The investigator's central hypothesis is that combined daily AIH (dAIH) and respiratory strength training will elicit greater and more sustained gains in respiratory function than either treatment alone in people with chronic SCI.

This study is a double-blind, randomized, cross-over design where participants will complete 4 random-ordered blocks, consisting of a 5-day intervention followed by a 3-week washout period, during which 1-day, 3-day, and 1-week post-tests will be conducted. Participants will include 53 adults with chronic, incomplete SCI with >20% respiratory impairment based on maximal inspiratory or expiratory pressure generation.

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alicia Vose, MA CCC-SLP; Phone Number: 860-912-8156; Email: avose1@ufl.edu
• Study Contact Backup: Name: Emily J Fox, DPT, PhD; Email: ejfox@ufl.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Recruiting
      • Brooks Rehabilitation Hospital
      • Contact: Lou DeMark, DPT; Phone Number: 904-345-8968; Email: lou.demark@brooksrehab.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chronic incomplete SCI for ≥ 1 year at or below C-1 to T-12
• 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 for ≥ 1 year at or below C-4 to T-12

• 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 clearance from physician
• SCI due to non-progressive etiology
• >20% impairment in maximal inspiratory or expiratory pressure generation, relative to established normative values.

Exclusion Criteria:

• Current diagnosis of an additional neurologic condition such as multiple sclerosis, Parkinson's disease, stroke, or brain injury
• Presence of unstable or uncontrolled medical conditions such as cardiovascular disease, myocardial infarction, <1 year lung disease, infections, hypertension, heterotopic ossification.
• Severe neuropathic pain
• Known pregnancy
• Severe recurrent autonomic dysreflexia
• History of seizure disorder < 1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adults with incomplete SCI; Adults with chronic, incomplete SCI who have >20% impairment in respiratory function, who will complete a battery of clinical assessments and 4 randomly ordered intervention and testing blocks (Daily AIH Block, Sham dAIH Block, Respiratory Strength Training Block and AIH + Strength Training Block).

Other: Daily AIH Block; Daily sessions of AIH (dAIH) with use of short episodes of low oxygen (9% O2); Other Names: dAIH Block; Other: Sham dAIH Block; Daily sessions of sham dAIH which includes breathing room air (21% O2); Other: Respiratory Strength Training Block; Respiratory strength training using a hand-held device that resists inspiration or expiration.; Other: AIH + Strength Training Block; AIH followed by respiratory strength training.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, Day 1, Day 6, Day 8, Day 15
Change in maximal expiratory pressure	Maximal expiratory pressure is a non-invasive measure of the maximal force generated when breathing out against an occluded airway.	Baseline, Day 1, Day 6, Day 8, Day 15

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: United States Department of Defense; Brooks Rehabilitation
• Investigators: Principal Investigator: Emily Fox, PT, PhD, University of Florida; Principal Investigator: Gordon Mitchell, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2020
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: February 6, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 7, 2019

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: breathing; respiration; motor function; plasticity; acute intermittent hypoxia (AIH); spinal neuroplasticity; respiratory strength training
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: IRB201802672; W81XWH-18-1-0718 (Other Grant/Funding Number: US Deptartment of Defense)

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