Acute Intermittent Hypoxia Combined With Gait Training in Multiple Sclerosis

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Other Acute Intermittent Hypoxia (AIH)
  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.
• Other Sham Acute Intermittent Hypoxia (AIH)
  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.
• Other Myoelectric Interface Neurorehabilitation Training (MINT)
  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 con

Primary outcome measures

• 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).]

Secondary outcome measures (5)

• 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)]
• 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]
• 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]
• 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]
• 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]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07631923 · STU00225287

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗