Acute Intermittent Hypoxia Combined With Gait Training in Multiple Sclerosis

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorShirley Ryan AbilityLab

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Acute Intermittent Hypoxia (AIH)

    Other intervention

    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 intervention

    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 intervention

    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

Treatment groups

35 Participants
are divided into 2 treatment groups
Group A: AIH + MINTActive comparator 2 interventions
Group B: SHAM AIH + MINTSham comparator 2 interventions

Trial outcomes

Primary outcomes

1

Six-Minute Walk Test (6MWT)

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

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).

Secondary outcomes

1

Ten-Meter Walk Test (10MWT)

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

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)
2

Stair Climb Test (SCT)

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.

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
3

Maximal Voluntary Contraction (MVC) Testing

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.

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
4

Fatigability Testing

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.

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

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

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