Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair

Our goal is to enhance repeated exposure to acute intermittent hypoxia (rAIH)/training-induced aftereffects on upper and lower limb function recovery in humans with chronic spinal cord injury (SCI).

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Other: Repeated exposure to acute Intermittent Hypoxia (rAIH); Other: Upper-limb Training by Research Staff; Other: Lower-limb Training by Research Staff; Other: Normal Room Air

Detailed Description

The experiments in this study will test the following: Hypothesis 1.1(Experiment 1) that rAIH will enhance corticospinal excitability and upper and lower limb function in humans with incomplete SCI. Hypothesis 1.2 (Experiment 2) that enhancing the aftereffects of rAIH with exercise training will further enhance upper and lower limb motor function in humans with incomplete SCI. Measurements of corticospinal, cortical, and motoneuron excitability will be tested to further understand the mechanisms of this induced-plasticity. Persons with chronic (>6 months) spinal cord injury between the levels of C2 and T2. SCI subjects must possess either the ability to produce a visible precision grip force with one hand, and/or the ability to perform some small wrist flexion and extension. Additionally, subject must possess the ability to perform a small visible contraction with dorsiflexion and hip flexor muscles. Controls must be right handed due to potential differences in the organization of the brain in right handed and left handed individuals.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Monica Perez, PhD; Phone Number: 312-238-2886; Email: mperez04@sralab.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Shirley Ryan AbilityLab
      • Contact: Monica Perez, PhD, PT; Phone Number: 312-238-2886; Email: mperez04@sralab.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria for SCI:

1. Males and females between 18-85 years
2. Chronic SCI (≥ 6 months post injury)
3. SCI at or above L2
4. ASIA A, B, C, or D, complete or incomplete
5. Possess the following: The ability to produce a visible precision grip force with one hand, and/or the ability to perform some small wrist flexion and extension. The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles.

Inclusion criteria for controls:

1. Males and females between 18-85 years
2. Right-handed (Only right-handed individuals will be accepted into this group because of the potential differences in the organization of the brain in right handed and left handed individuals)

Exclusion criteria for SCI and for controls:

1. Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
2. Any debilitating disease prior to the SCI that caused exercise intolerance
3. Premorbid, ongoing major depression or psychosis, altered cognitive status
4. History of head injury or stroke
5. Metal plate in skull
6. History of seizures
7. Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressant
8. Pregnant females
9. Ongoing cord compression or a syrinx in the spinal cord or a spinal cord disease as spinal stenosis, spina bifida or herniated cervical disk.

AIH exclusion criteria (in addition to the above listed exclusion criteria)

1. Resting heart rate ≥120 BPM
2. Resting systolic blood pressure >180 mm Hg
3. Resting diastolic Blood Pressure >100 mmHg
4. Self-reported history of unstable angina or myocardial infarction within the previous month
5. Resting SpO2 ≥ 95%
6. Cardiopulmonary complications such as COPD

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rAIH + training by research staff; Participants will receive repeated exposure to acute Intermittent Hypoxia (rAIH) and training by research staff.	Other: Repeated exposure to acute Intermittent Hypoxia (rAIH); Participants will be fitted with a mask that will be placed over mouth and nose. Tubing will be attached to the front of the mask. The session will last approximately 30-45 minutes with 60-90 seconds of lower oxygen (tubing attached, 9-10% oxygen level), alternating with 60-90 sec of normal room air (no tubing attached).; Other: Upper-limb Training by Research Staff; Training sessions will last for approximately 30 minutes, with additional time for set up. During these sessions, participants will be asked to complete a variety of tasks related to general arm/hand movement, gross grasping, fine grasping, and hand cycle using an arm ergometer. The number of repetitions will be monitored and adjust the difficulty to ensure appropriate task difficulty.; Other: Lower-limb Training by Research Staff; Training sessions will last for approximately 30 minutes, with additional time for set up. During these sessions, participants will be asked to complete a variety of tasks related to general leg/foot movement, over-ground walking, treadmill walking, stair climbing training, leg cycling, standing frame, and NuStep. The number of repetitions will be monitored and adjust the difficulty to ensure appropriate task difficulty.
Sham Comparator: sham rAIH + training; Participants will sham receive repeated exposure to acute Intermittent Hypoxia (rAIH) and training by the research staff.	Other: Upper-limb Training by Research Staff; Training sessions will last for approximately 30 minutes, with additional time for set up. During these sessions, participants will be asked to complete a variety of tasks related to general arm/hand movement, gross grasping, fine grasping, and hand cycle using an arm ergometer. The number of repetitions will be monitored and adjust the difficulty to ensure appropriate task difficulty.; Other: Lower-limb Training by Research Staff; Training sessions will last for approximately 30 minutes, with additional time for set up. During these sessions, participants will be asked to complete a variety of tasks related to general leg/foot movement, over-ground walking, treadmill walking, stair climbing training, leg cycling, standing frame, and NuStep. The number of repetitions will be monitored and adjust the difficulty to ensure appropriate task difficulty.; Other: Normal Room Air; Participants will be fitted with a mask that will be placed over mouth and nose. Tubing will be attached to the front of the mask. The session will last approximately 30-45 minutes with 60-90 seconds of normal room air (with tubing attached to the mask) and 60-90 sec of normal room air (without the tubing attached to the mask).; Other Names: Sham repeated exposure to acute Intermittent Hypoxia (rAIH)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper limb functional measurement	The Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) will be used to assess sensation, strength, and prehension.	45 minutes to 1 hour
Lower limb functional measurement	10-meter walk test will be used to assess walking speed	5-10 minutes
MEP/CMEP recruitment curves using TMS	Ten Transcranial magnetic stimuli (TMS) will be delivered to plot the mean peak-to-peak amplitude of the motor and cervicomedullary evoked potentials (MEPs and CMEPs, respectively) from the non-rectified response against the TMS intensity in each subject (MEP/CMEP recruitment curves).	30 minutes to 1 hour
EMG and force voluntary output	EMG surface electrodes will be placed over target muscles (deltoid, biceps brachii, first dorsal interosseous, abductor pollicis brevis, quadriceps femoris, tibialis anterior and/or soleus) to measure maximum voluntary contraction (MVC)	30 minutes to 1 hour

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab
• Collaborators: U.S. Department of Education
• Investigators: Principal Investigator: Monica A Perez, PhD, Shirley Ryan AbilityLab

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2020
• Primary Completion (Anticipated): December 28, 2024
• Study Completion (Anticipated): December 28, 2025

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 14, 2018

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Acute Intermittent Hypoxia
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Signs and Symptoms, Respiratory; Spinal Cord Diseases; Spinal Cord Injuries; Hypoxia
• Other Study ID Numbers: STU00212000

Drug and device information, study documents

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