AIH + NMES for Multiple Sclerosis

Overseen By Rachel A Kravitt, OTD, OTR/L

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shirley Ryan AbilityLab

Must not be taking: Antipsychotics, Tricyclic antidepressants

Disqualifiers: Epilepsy, Stroke, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two treatments—acute intermittent hypoxia (short bursts of low oxygen) and neuromuscular electrical stimulation (NMES, which uses electrical impulses to stimulate muscles)—might work together to help people with a relapsing form of multiple sclerosis (MS). Researchers aim to determine if these treatments can enhance brain and spinal cord activity, potentially leading to more effective MS therapies in the future. The study will compare the effects of using each treatment alone and in combination. Individuals diagnosed with relapsing MS, who have had no flare-ups for at least a year and experience significant mobility challenges, may be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research that could shape future MS therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking drugs that affect the central nervous system and lower the seizure threshold, like certain antipsychotics or tricyclic antidepressants.

What prior data suggests that this protocol is safe for people with multiple sclerosis?

Research shows that both acute intermittent hypoxia (AIH) and neuromuscular electrical stimulation (NMES) are generally well-tolerated by people with multiple sclerosis (MS). Studies have found that AIH can safely increase ankle strength in MS patients without affecting their thinking or brain blood flow. Participants in AIH studies completed the sessions without major problems.

For NMES, research confirms it is safe for people with moderate-to-severe MS, even if they cannot walk. NMES helps maintain muscle strength and does not seem to cause serious side effects.

Although researchers are testing AIH and NMES together for potential benefits, previous research on each treatment alone suggests they are safe to use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring Acute Intermittent Hypoxia (AIH) and Neuromuscular Electrical Stimulation (NMES) for multiple sclerosis (MS) because these treatments offer unique approaches compared to standard medications like interferons or monoclonal antibodies. AIH involves brief exposure to low oxygen levels, which might enhance nerve repair and function. Meanwhile, NMES delivers electrical impulses to stimulate nerves and muscles, potentially improving movement and strength. Combining AIH and NMES could amplify these benefits, offering a non-drug alternative that directly targets nerve and muscle function, providing a fresh approach to managing MS symptoms.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that neuromuscular electrical stimulation (NMES), one of the treatments in this trial, can help people with multiple sclerosis (MS) by strengthening muscles and improving their function. Studies have found that NMES can increase muscle size and enhance mobility. Another treatment in this trial, acute intermittent hypoxia (AIH), has been shown to strengthen ankles and help the brain form new connections. This trial will also test the combination of AIH and NMES, which might provide even greater benefits, potentially enhancing brain activity and muscle function more than using each treatment alone. This combination aims to improve the coordination between the brain and spinal cord, which is crucial for controlling movement. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with relapsing multiple sclerosis. Participants should be able to perform the required physical tasks and have no other health conditions that could interfere with the study.

Inclusion Criteria

My Dalfampridine dose has been stable for at least 2 months.

I have been free from cancer relapse for at least 1 year.

My condition is a relapsing form of multiple sclerosis.

Exclusion Criteria

I have a neurological condition not related to MS.

I often have severe or unexplained headaches.

Pregnancy in females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo NMES, AIH, or combined AIH and NMES interventions to enhance corticospinal excitability

1 day per session

1 visit (in-person) per session

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acute Intermittent Hypoxia
• Neuromuscular Electrical Stimulation

Trial Overview The study is testing how well neuromuscular electrical stimulation (NMES) works when combined with acute intermittent hypoxia (AIH). It's looking at muscle strength and nerve responses in people with MS, comparing NMES alone, AIH alone, and both together.

How Is the Trial Designed?

Group I: NMES alone Experimental Treatment 1 Intervention

Participants will undergo repetitive common peroneal nerve stimulation for up to 30 minutes.

Group II: Combined AIH and NMES Experimental Treatment 2 Interventions

Participants will undergo 30 minutes of AIH. Immediately following, participants will undergo NMES for up to 30 minutes.

Group III: AIH alone Experimental Treatment 1 Intervention

Participants will undergo 30 minutes of AIH.

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

Therapeutic acute intermittent hypoxia (tAIH) shows promise in improving both respiratory and non-respiratory motor functions in individuals with neuromuscular disorders, particularly those with chronic spinal cord injuries, as highlighted in recent workshops aimed at clinical translation.

Key recommendations for advancing tAIH include enhancing our understanding of its mechanisms, optimizing treatment protocols, identifying effective combinatorial therapies, and ensuring long-term safety, which are essential for its potential routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. Vose, AK., Welch, JF., Nair, J., et al.[2023]

Acute intermittent hypoxia (AIH) is a safe treatment that involves alternating between low and normal oxygen levels, but in this study, it did not significantly change the excitability of the primary motor cortex in healthy participants.

Despite a notable drop in arterial oxygen saturation during AIH, there were no measurable effects on corticospinal excitability or intracortical circuits, suggesting that AIH may need to be adjusted in severity or tailored to individuals for potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex. Radia, S., Vallence, AM., Fujiyama, H., et al.[2022]

Acute intermittent hypoxia (AIH) significantly improved functional recovery and reduced inflammation in a mouse model of Multiple Sclerosis (EAE), indicating its potential as a non-invasive therapy for CNS repair.

AIH enhanced myelination and recruited oligodendrocyte precursor cells to demyelinated areas, suggesting it could alter the disease course and promote neuroregeneration in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute intermittent hypoxia alters disease course and promotes CNS repair including resolution of inflammation and remyelination in the experimental autoimmune encephalomyelitis model of MS. Tokarska, N., Naniong, JMA., Johnston, JM., et al.[2023]

Neuromuscular electrical stimulation (NMES) is a safe and effective method for enhancing muscle function, capable of inducing physiological adaptations like muscle hypertrophy and angiogenesis, even in populations unable to perform rigorous exercise.

The study outlines a protocol for using NMES in a murine model, which allows for precise control and feedback in muscle stimulation, demonstrating its applicability in both clinical and research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A murine model of muscle training by neuromuscular electrical stimulation. Ambrosio, F., Fitzgerald, GK., Ferrari, R., et al.[2021]

The neuromuscular electrical stimulation (NMES) protocol applied to critical ill patients was found to be safe, with no significant changes in muscle damage markers (creatine phosphokinase) or other safety indicators (central venous oxygen saturation and serum lactate) over the study period.

The NMES protocol was also feasible, with patients completing 85% of the planned sessions in an average time of 107 minutes, indicating that this treatment can be effectively integrated into the care of critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of a neuromuscular electrical stimulation chronaxie-based protocol in critical ill patients: A prospective observational study. Silva, PE., Babault, N., Mazullo, JB., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11090437/

Unraveling the potential of acute intermittent hypoxia as a ... With respect to efficient remyelination of the nerve, AIH therapy resulted in decreased numbers of degenerating myelin profiles and an improved G-ratio, a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06390930

Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS Research has found AIH to be a safe and effective intervention resulting in increased ankle strength in people with MS. Here, the study examines ...

3. medrxiv.org medrxiv.org/content/10.1101/2024.02.17.24302733v1

Acute Intermittent Hypoxia Induces Motor and Cognitive ... This study explores acute intermittent hypoxia (AIH) as a novel intervention for enhancing neuroplasticity and functional improvement in individuals with MS.

4. msard-journal.com msard-journal.com/article/S2211-0348(23)00151-7/fulltext

Acute Intermittent Hypoxia and UE Strength and Function ... AIH treatment was well tolerated by our participant and a single bout of AIH resulted in positive changes in UE strength and function on her more involved side.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12146665/

Hypoxia in multiple sclerosis - PMC - PubMed Central - NIH However, therapeutic acute intermittent hypoxia is thought to act primarily via improving synaptic plasticity thereby contributing to improved ...

6. medrxiv.org medrxiv.org/content/10.1101/2025.09.24.25336487v1

Safety and potential benefits of acute intermittent hypoxia ... Results All participants tolerated the AIH sessions well and were able to complete the entire protocol. No significant improvement in cognition ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1569904824001514

Safety and effectiveness of acute intermittent hypoxia ... AIH is generally safe and effective for inducing neural plastic responses. · AIH does not impact cognition or cerebral perfusion rates. · AIH acutely results in a ...