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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine how neuromuscular electrical stimulation (NMES), may synergistically enhance corticospinal excitability in people with relapsing form multiple sclerosis (MS). This is an important intermediate step to evaluate the potential of AIH + NMES as a plasticity-priming strategy for more efficacious interventions for persons with MS. This study will measure ankle torque generation and amplitude of motor evoked potentials (MEPs) using a repeated measures study design in order to better understand the effects of AIH combined with NMES, as compared to only receiving NMES, and only receiving AIH.

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 data supports the effectiveness of the treatment AIH + NMES for Multiple Sclerosis?

The research suggests that neuromuscular electrical stimulation (NMES) can help reduce muscle fatigue in some people, although it may increase fatigue in others. However, there is no clear evidence from the studies that NMES leads to long-term strength improvements in people with multiple sclerosis. ^{1 2 3 4 5}

Is neuromuscular electrical stimulation (NMES) safe for humans?

NMES is generally considered safe for humans, even for those who are ill or bedridden, although it may cause discomfort and is not recommended for people with certain conditions like peripheral venous disorders or malignancy. It has been used safely in various settings, including sports medicine and rehabilitation, and studies have shown it to be feasible in critically ill patients. ^{1 3 6 7 8}

How does the AIH + NMES treatment for Multiple Sclerosis differ from other treatments?

The AIH + NMES treatment is unique because it combines acute intermittent hypoxia (AIH), which involves brief periods of breathing low-oxygen air, with neuromuscular electrical stimulation (NMES) to enhance nerve repair and reduce inflammation in Multiple Sclerosis. This non-invasive approach aims to promote remyelination and improve motor function, offering a novel strategy compared to traditional treatments. ^{9 10 11 12 13}

Eligibility Criteria

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.

My condition is a relapsing form of multiple sclerosis.

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

Exclusion Criteria

I have a neurological condition not related to MS.

I often have severe or unexplained headaches.

Pregnancy in females

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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) 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]

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Contraction fatigue, strength adaptations, and discomfort during conventional versus wide-pulse, high-frequency, neuromuscular electrical stimulation: a systematic review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Torque, Current, and Discomfort During 3 Types of Neuromuscular Electrical Stimulation of Tibialis Anterior. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and feasibility of a neuromuscular electrical stimulation chronaxie-based protocol in critical ill patients: A prospective observational study. [2018]

4. Canada pubmed.ncbi.nlm.nih.gov

Decreased excitability of motor axons contributes substantially to contraction fatigability during neuromuscular electrical stimulation. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of neuromuscular electrical stimulation on arterial hemodynamic properties and body composition in paretic upper extremities of patients with subacute stroke. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

A murine model of muscle training by neuromuscular electrical stimulation. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Effects of electrode size and placement on comfort and efficiency during low-intensity neuromuscular electrical stimulation of quadriceps, hamstrings and gluteal muscles. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Neuromuscular electrical stimulation. An overview and its application in the treatment of sports injuries. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of acute intermittent hypoxia on cortico-diaphragmatic conduction in healthy humans. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Autophagy-associated atrophy and metabolic remodeling of the mouse diaphragm after short-term intermittent hypoxia. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. [2023]

12. United States 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. [2023]

13. Germany pubmed.ncbi.nlm.nih.gov

Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex. [2022]