Effect of a Novel Intervention Using Daily Intermittent Hypoxia and High Intensity Training on Upper Limb Function in Individuals With Spinal Cord Injury

Currently, there are a variety of approaches utilized in attempts to improve upper extremity function, including: traditional therapy, neuroprostheses, botulinum toxin injections, or surgical interventions. In addition, regenerative and restorative therapies, such as: epidural stimulation, functional electrical stimulation, and stem cell therapies, show promise in animal models, but are not ready for clinical translation. Subsequently, there is a clear need to develop new strategies that can stimulate spinal plasticity and strengthen existing synaptic connections in order to maximize the benefits of training paradigms.

This study proposes the examine the effects of Acute Intermittent Hypoxia (AIH) in combination with upper extremity training, over the course of a month, to evaluate changes in upper extremity function, dexterity, and ability to complete activities of daily living. The use of acute intermittent hypoxia (AIH) has been demonstrated, through human and animal studies, to be an effective way of increasing spinal motor excitability and strengthening residual synaptic connectivity. AIH utilizes short duration (<2 min) exposures to reduced oxygen levels (~10% inspired oxygen), with alternating exposures to air with normal oxygen levels (~21% inspired oxygen).

Previous publications demonstrate that AIH is a safe and effective intervention to modify motor function in individual with chronic incomplete spinal cord injuries. The use of AIH has been shown to influence the activation in musculature, within 60-120 minutes of administration. In addition, when coupling AIH with overground gait training, an increase in functional endurance, as evaluated through the 6 minute walk test, and gait speed, as evaluated through the 10 meter walk test, were demonstrated. In addition, the use of hypoxic training has been studied in healthy individuals and athletes; however, literature examining the effect of a single bout of AIH on performance is limited.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Combination product: Upper extremity training/Armeo Spring

Detailed Description

This study proposes the examine the effects of Acute Intermittent Hypoxia (AIH) in combination with upper extremity training, over the course of a month, to evaluate changes in upper extremity function, dexterity, and ability to complete activities of daily living. The use of acute intermittent hypoxia (AIH) has been demonstrated, through human and animal studies, to be an effective way of increasing spinal motor excitability and strengthening residual synaptic connectivity. AIH utilizes short duration (<2 min) exposures to reduced oxygen levels (~10% inspired oxygen), with alternating exposures to air with normal oxygen levels (~21% inspired oxygen).

Previous publications demonstrate that AIH is a safe and effective intervention to modify motor function in individual with chronic incomplete spinal cord injuries. The use of AIH has been shown to influence the activation in musculature, within 60-120 minutes of administration. In addition, when coupling AIH with overground gait training, an increase in functional endurance, as evaluated through the 6 minute walk test, and gait speed, as evaluated through the 10 meter walk test, were demonstrated. In addition, the use of hypoxic training has been studied in healthy individuals and athletes; however, literature examining the effect of a single bout of AIH on performance is limited.

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Alexander Barrry; Phone Number: 312-238-1435; Email: abarry@sralab.org
• Study Contact Backup: Name: Zev Rymer, MD; Email: zrymer@sralab.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Shirley Ryan AbilityLab
      • Contact: Alexander Barry, MS, CCRC; Phone Number: 312-238-1435; Email: abarry@sralab.org
      • Principal Investigator: William Z Rymer, MD/PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• History of a non-progressive spinal cord injury, inclusive of levels of C1-T1.
• Etiology of spinal cord injury is non-progressive in nature
• Be able to demonstrate some hand muscle activation, or use of a tenodesis grasp (wrist extension)
• At least 6 months post injury
• Participants do NOT have to stop taking antispasticity medications to participate in the study.
• Must be tested for anemia with a value of at least 10g/dl (for both men and women).
• Patients will be recommended to their primary care physician to correct anemia if low levels are detected
• Blood pressure must fall within this range- high: 160/110mmHg low: 85/55 mmHg
• Must be asymptomatic (no dizziness, lightheadedness, etc)

Exclusion Criteria:

• Medical conditions, including: congestive heart failure, cardiac arrhythmias, uncontrolled hypertension, uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, emphysema, severe asthma, previous myocardial infraction, or known carotid/intracerebral artery stenosis.
• Women who are currently pregnant or planning on becoming pregnant
• Current tracheostomy placement
• Utilization of mechanical ventilator for breathing
• Current diagnosis of obstructive sleep apnea
• Orthopedic injuries or surgeries that would limit participation
• Concurrent participation in another research study or therapy services
• Comorbid traumatic brain injury or other neurologic injuries that would impact cognition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Acute Intermittent Hypoxia (AIH) treatment; The mask will first provide a normoxic air (room air) mixture (FiO2 = 0.21) via the mask. The mask is designed to couple with a universal mask circuit connecting to the air mixture system. The purpose of the mask will be to minimize room air entrainment.
Active Comparator: AIH in combination with upper extremity training; The mask will first provide a normoxic air (room air) mixture (FiO2 = 0.21) via the mask. The mask is designed to couple with a universal mask circuit connecting to the air mixture system. The purpose of the mask will be to minimize room air entrainment. In addition to this upper extremity training will be given using an upper-limb robotic rehabilitation device.	Combination product: Upper extremity training/Armeo Spring; Armeo Spring is a gravity support system based on an ergonomic arm exoskeleton with integrated springs.
Active Comparator: Sham AIH therapy in combination with upper extremity training; Sham hypoxia followed by upper extremity training will be given using an upper-limb robotic rehabilitation device (Armeo Spring®, Hocoma AG, Switzerland). Armeo Spring is a gravity support system based on an ergonomic arm exoskeleton with integrated springs.	Combination product: Upper extremity training/Armeo Spring; Armeo Spring is a gravity support system based on an ergonomic arm exoskeleton with integrated springs.
No Intervention: Sham AIH therapy; Sham hypoxia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GRASSP	Graded Redefined Assessment of Strength, Sensation and Prehension	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
9-hole peg test	coordination	4 weeks
grip strength	hand strength	4 weeks

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2018
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 23, 2018

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: hypoxia
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Signs and Symptoms, Respiratory; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries; Hypoxia
• Other Study ID Numbers: STU 00206035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No