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NCT Number: NCT07631923

Acute Intermittent Hypoxia Combined With Gait Training in Multiple Sclerosis

This interventional, randomized, sham-controlled study will examine whether Acute Intermittent Hypoxia (AIH) delivered immediately before Myoelectric Interface Neurorehabilitation Training (MINT)-based locomotor training improves gait in people with Multiple Sclerosis. The primary objectives are to evaluate changes in gait speed and endurance, with secondary objectives assessing spatiotemporal gait parameters, fatigue, and safety. Participants will receive AIH or sham priming followed by standardized treadmill and/or overground gait training, with outcome measures collected before and after the intervention across multiple sessions.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Chronic Disease Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Disease Attributes Hypoxia Immune System Diseases Multiple Sclerosis (MS) - Relapsing-remitting Multiple Sclerosis (MS) Primary Progressive Multiple Sclerosis (MS) Secondary Progressive Multiple Sclerosis, Chronic Progressive Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Respiratory

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

The study tests whether a brief breathing treatment, acute intermittent hypoxia (AIH), can make a computer-based muscle training program (MINT) more effective for people with MS who have difficulty walking. AIH involves breathing short alternating periods of low-oxygen air (about 9% oxygen versus the roughly 21% in room air) and normal room air. The premise, drawn from work in other neurological conditions like spinal cord injury, is that AIH delivered before movement training may improve strength and walking. Whether this benefits people with MS is not yet known, which is the gap the study addresses.

MINT itself uses surface EMG sensors on the leg muscles to capture muscle activity, which then controls game-like tasks on a screen. Participants practice activating the correct muscles for walking while suppressing unwanted activity.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of clinically definite multiple sclerosis
  • Patient-Determined Disease Steps (PDDS) score between 3 and 6
  • Relapse-free for at least 6 months prior to enrollment
  • Age ≥ 18 years and ≤ 75 years
  • Resting oxygen saturation (SpO₂) ≥ 95% on room air
  • Systolic blood pressure between 85-140 mmHg and diastolic blood pressure between 55-90 mmHg
  • Modified Ashworth Scale (MAS) score ≤ 3 at the ankle and knee
  • Mini-Mental State Examination (MMSE) score ≥ 24
  • Ability to walk at least 10 meters with or without an assistive device
  • Ability to perform active ankle dorsiflexion and plantarflexion

Exclusion criteria

  • Uncontrolled hypertension or hypotension outside the required ranges
  • History of epilepsy or seizures
  • Uncontrolled pulmonary, cardiovascular, or orthopedic disease
  • Premorbid or ongoing major psychiatric illness (e.g., major depression, psychosis)
  • Other neurological disease (e.g., stroke, traumatic brain injury, peripheral neuropathy)
  • Illnesses with potential to cause brain injury
  • Frequent or severe unexplained headaches
  • Pregnancy
  • Implanted medical devices (e.g., pacemakers, intrathecal pumps, brain stimulators)

Treatment and study plan

Acute Intermittent Hypoxia (AIH)

Other

During AIH, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The AIH intervention involves alternating breathing cycles. One cycle involves breathing air with lower oxygen concentration (9-10% oxygen) for 30 and 90 seconds, followed by breathing normal room air (21% oxygen) for a similar duration. This cycle is repeated 15 times in one session. Blood oxygen and heart rate are monitored throughout.

Sham Acute Intermittent Hypoxia (AIH)

Other

During Sham AIH, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The Sham AIH intervention involves alternating breathing cycles. One cycle involves breathing air closely resembling room air (~21% oxygen) for 30 and 90 seconds, followed by breathing normal room air (21% oxygen) for a similar duration. This cycle is repeated 15 times in one session. Blood oxygen and heart rate are monitored throughout.

Myoelectric Interface Neurorehabilitation Training (MINT)

Other

MINT is a gamified rehabilitation paradigm that uses surface electromyography (sEMG) biofeedback to retrain lower-limb muscle activation patterns. The intervention is designed to reduce abnormal coactivation of agonist-antagonist muscle pairs and facilitate more efficient torque generation during functional movements.

sEMG electrodes will be placed bilaterally over the tibialis anterior, gastrocnemius, and quadriceps muscles. EMG signals will be acquired in real time, processed, and used to control on-screen tasks within a custom Unity-based software environment. Participants will engage in interactive tasks where selective activation of target muscles allows them to move a virtual avatar, align a gauge, or achieve movement goals while minimizing antagonist activity.

Each MINT session will last approximately 60 minutes and will be delivered immediately following AIH or sham exposure. Sessions will include calibration of EMG channels, a brief familiarization period, and four to five tra

Primary outcomes

  1. Six-Minute Walk Test (6MWT)

    Time frame: Change in distance (meters) from pre-training assessment (Day 1, before the first intervention) to Immediate Post (Day 5, after the final intervention), 1-week follow-up (Day 14-21), and 1-month follow-up (Day 36-41).

    Participants walk as far as they safely can in six minutes along a marked course, and total distance (meters) is recorded.

Secondary outcomes

  1. Ten-Meter Walk Test (10MWT)

    Time frame: Baseline/pre-training (Day 1) to immediately post-intervention (Day 5), with retention assessed at the 1-week (Day 14 to 21) and 1-month (Day 36 to 41)

    Measures gait speed over 10 meters at a self-selected comfortable pace, averaged across two trials.

  2. Stair Climb Test (SCT)

    Time frame: Baseline/pre-training (Day 1) to immediately post-intervention (Day 5), then 1-week (Day 14 to 21) and 1-month (Day 36 to 41) follow-ups

    Assesses functional mobility and lower-limb power. Participants ascend a standardized 12-step staircase (17 cm per step, 2.04 m total) as quickly and safely as possible across three trials, with ascent time recorded and handrail use documented.

  3. Maximal Voluntary Contraction (MVC) Testing

    Time frame: Baseline/pre-training (Day 1) to immediately post-intervention (Day 5), then 1-week (Day 14 to 21) and 1-month (Day 36 to 41) follow-ups

    Measures maximal strength of the trained leg on a Biodex dynamometer across ankle plantarflexion, dorsiflexion, knee flexion, and knee extension. Participants perform 3 to 5 maximal isometric contractions (10 seconds each) per movement while surface EMG quantifies agonist activation and antagonist coactivation.

  4. Fatigability Testing

    Time frame: Baseline/pre-training (Day 1) to immediately post-intervention (Day 5), then 1-week (Day 14 to 21) and 1-month (Day 36 to 41) follow-ups

    Quantifies muscle fatigue as the percent decline in torque across 20 consecutive maximal isometric plantarflexion contractions (5 to 10 seconds each) on the Biodex, with surface EMG monitoring changes in activation and coactivation through the series.

  5. Ankle Proprioception Testing

    Time frame: aseline/pre-training (Day 1) to immediately post-intervention (Day 5), then 1-week (Day 14 to 21) and 1-month (Day 36 to 41) follow-ups

    Assesses joint sense on the trained leg via the Biodex while the participant is blindfolded with noise-cancelling headphones. It includes a movement detection threshold (trigger press when slow passive rotation is first felt, 5 to 6 trials) and joint position matching (reproducing a passively set target angle, 6 to 8 trials), with surface EMG confirming no compensatory activity.

Study contacts

Contact information is provided by the study sponsor or research team.

Rachel A Kalvakota, OTD, OTR/L

CONTACT

[email protected]

1-312-238-3947

Sponsors and collaborators

Lead sponsor

Shirley Ryan AbilityLab

Other

Registry information

Official study title

Acute Intermittent Hypoxia (AIH) Primed Myoelectric Interface Neurorehabilitation Training (MINT) for Gait Recovery in Multiple Sclerosis

Acronym: MINT

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jun 8, 2026
Registry last updated
Jun 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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