The Effect of Acute Intermittent Hypoxia on Motor Learning

Examining the Relationship Between Changes in Corticospinal Excitability and Motor Learning After Acute Intermittent Hypoxia in Able-bodied Individuals for Subsequent Study in Individuals With Incomplete Spinal Cord Injury.

The goal of this study is to examine the effect of repetitive acute intermittent hypoxia on motor learning abilities in able-bodied individuals for subsequent study in individuals with incomplete spinal cord injury.

Study Overview

• Status: Completed
• Conditions: Incomplete Spinal Cord Injury
• Intervention / Treatment: Other: Acute Intermittent Hypoxia; Other: SHAM Acute Intermittent Hypoxia

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Anschutz Medical Campus
    • Boulder, Colorado, United States, 80309
      • University of Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 to 70 years old (the latter to reduce likelihood of heart disease);
• Medically stable with medical clearance from physician to participate;
• Motor-incomplete spinal cord injuries at or below C2 and at or above L5;
• AIS A-D at initial screen, or other non-traumatic spinal cord injury disorders (e.g. multiple sclerosis, ALS, tumors, acute transverse myelitis, etc.);
• More than 1 year since iSCI to minimize confounds of spontaneous neurological recovery;
• Ability to advance one step overground with or without assistive devices;

Exclusion Criteria:

• Severe concurrent illness or pain;
• Recurrent autonomic dysreflexia;
• History of cardiovascular/pulmonary complications;
• Concurrent physical therapy;
• Pregnant at time of enrollment or planning to become pregnant;
• Untreated painful musculoskeletal dysfunction, fracture or pressure sore;
• History of seizures or epilepsy;
• Recurring headaches;
• Concussion within the last six months;
• Depression or manic disorders
• Metal implants in the head, or pacemaker.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Repetitive Acute Intermittent Hypoxia; 5 consecutive days of 15, 1.5 min episodes at 9% O2 (AIH) alternating with 21% O2 at 1 min intervals	Other: Acute Intermittent Hypoxia; 5 consecutive days of 15, 1.5 min episodes at 9% O2 (AIH) alternating with 21% O2 at 1 min intervals
Sham Comparator: SHAM Acute Intermittent Hypoxia; 5 consecutive days of 15, 1.5 min episodes at 21% O2 (SHAM AIH) alternating with 21% O2 at 1 min intervals	Other: SHAM Acute Intermittent Hypoxia; 5 consecutive days of 15, 1.5 min episodes at 21% O2 (SHAM AIH) alternating with 21% O2 at 1 min intervals
No Intervention: Control; The control group received no AIH exposure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Corticospinal Excitability	Transcranial magnetic stimulation (TMS) can be applied over the primary motor cortex to examine changes in corticospinal excitability. The downstream muscle activation can be recorded with surface EMG as a motor-evoked potential (MEP). The peak-to-peak MEP amplitude (mV) is as an index of corticospinal excitability. A randomized sequence of TMS intensities can be applied over the primary motor cortex, ranging from 90-140% of the participants' resting motor threshold (RMT). The mean MEP amplitude will be plotted against the corresponding stimulation intensity to produce the recruitment curve. The area under the recruitment curve is an additional index of corticospinal excitability (mV/% RMT).	We will measure TMS before the start of 5 consecutive days of AIH or SHAM treatment. We will measure TMS within 24 hours of the final treatment.
Step Length Asymmetry	Step length asymmetry will be quantified as the ratio of the normalized difference in step lengths between the fast and slow legs during split-belt motor adaptation: (Fast leg - Slow leg step length) / (Fast leg + Slow leg step length).	We will compare asymmetry 15 minutes after the final AIH treatment to asymmetry following no treatment (control group).
Step Time Asymmetry	Step time asymmetry will be quantified as the ratio of the normalized difference in step times between the fast and slow legs during split-belt motor adaptation: (Fast leg - Slow leg step time) / (Fast leg + Slow leg step time).	We will compare asymmetry 15 minutes after the final AIH treatment to asymmetry following no treatment (control group).
Net Metabolic Power	Using expired gas analyses, we will calculate net metabolic power by inputting steady-state values for V̇O₂ and V̇CO₂ into standard regression equations (W), subtracting resting values, and normalizing the result to each participant's body weight (kg).	We will compare net metabolic power 15 minutes after the final AIH treatment to asymmetry following no treatment (control group).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Muscle Surface Electromyography	Muscle activation will be recording using surface EMG, and quantified as the activation amplitude and activation timing of the leg muscles during walking assessments. EMG amplitude will be normalized to maximum contraction during walking and activation will be normalized to the gait cycle. We will record EMG's of the muscles that contribute to ankle and knee joint torque production.	We will measure EMG during a baseline walking assessment before the start of 5 consecutive days of AIH treatment. We will measure EMG during a post walking assesment within 24 hours after the final AIH treatment.
Change in Leg Kinematics	The relative ankle, knee, and hip joint angle excursions throughout the gait cycle will be quantified during walking assessments.	We will measure kinematics during a baseline walking assessment before the start of 5 consecutive days of AIH treatment. We will measure kinematics during a post walking assesment within 24 hours after the final AIH treatment.

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Collaborators: Medical University of South Carolina; University of Colorado, Denver; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

General Publications

• Bogard AT, Hembree TG, Pollet AK, Smith AC, Ryder SC, Marzloff GE, Tan AQ. Intermittent hypoxia-induced enhancements in corticospinal excitability predict gains in motor learning and metabolic efficiency. Sci Rep. 2025 Feb 24;15(1):6614. doi: 10.1038/s41598-025-90890-8.
• Bogard AT, Hemmerle MR, Smith AC, Tan AQ. Enhanced motor learning and motor savings after acute intermittent hypoxia are associated with a reduction in metabolic cost. J Physiol. 2024 Nov;602(21):5879-5899. doi: 10.1113/JP285425. Epub 2023 Nov 20.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): February 24, 2025

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: April 15, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Spinal Cord Injury; Acute Intermittent Hypoxia; Motor Adaptation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Signs and Symptoms, Respiratory; Trauma, Nervous System; Spinal Cord Diseases; Hypoxia; Spinal Cord Injuries
• Other Study ID Numbers: 21-3980; P2CHD086844 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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