Acute Intermittent Hypoxia Combined With Gait Training in Multiple Sclerosis

NCT07631923 | Not Yet Recruiting

• 1 other identifier: STU00225287
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Multiple Sclerosis; Multiple Sclerosis (MS) Secondary Progressive; Multiple Sclerosis (MS) - Relapsing-remitting; Multiple Sclerosis (MS) Primary Progressive

Keywords

hypoxia; neuroplasticity; rehabilitation; gait; recovery; walking; walk; lower extremities; strength; AIH

Outcome Measures

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.

  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 (5)

• Ten-Meter Walk Test (10MWT)

  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)

  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

  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

  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

  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

Study Arms (2)

AIH + MINT

ACTIVE COMPARATOR

Other: Acute Intermittent Hypoxia (AIH); Other: Myoelectric Interface Neurorehabilitation Training (MINT)

SHAM AIH + MINT

SHAM COMPARATOR

Other: Sham Acute Intermittent Hypoxia (AIH); Other: Myoelectric Interface Neurorehabilitation Training (MINT)

Interventions

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.

AIH + MINT

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.

SHAM AIH + MINT

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

AIH + MINT; SHAM AIH + MINT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Shirley Ryan AbilityLab: lead

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Hypoxia

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Study Officials

• Milap Sandhu, PT, PhD

  Shirley Ryan AbilityLab

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel A Kalvakota, OTD, OTR/L

CONTACT

1-312-238-3947; rkalvakota@sralab.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 8, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share