Acute Intermittent Hypoxia for Multiple Sclerosis

Overseen By rachel Kravitt, OTD, OTR/L

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shirley Ryan AbilityLab

Must be taking: Disease modifying therapies

Disqualifiers: Peripheral neuropathies, Epilepsy, COPD, others

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a unique breathing technique, called Acute Intermittent Hypoxia (AIH), affects arm and hand function in people with multiple sclerosis (MS). AIH involves breathing in short bursts of low oxygen. Past research has shown it can boost ankle strength in those with MS. Researchers aim to determine if AIH can also improve arm function and how the brain and spinal cord respond to it. Individuals with relapsing-remitting MS, who haven't experienced a relapse in at least six months and have some difficulty with finger or hand tasks, might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance MS treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have stable disease-modifying therapies for at least 6 months, and if you're taking dalfampridine, it should be the same dose for at least 2 months before screening.

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

Research has shown that Acute Intermittent Hypoxia (AIH), a breathing exercise, is generally safe for people with multiple sclerosis (MS). Studies have found that participants handle AIH easily, with no major problems during the sessions. No significant side effects have been reported, and it does not harm brain function or blood flow. In fact, AIH has been linked to benefits like stronger ankle muscles, indicating it can safely help build muscle strength. Overall, AIH appears to be a safe choice for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Acute Intermittent Hypoxia (AIH) for multiple sclerosis (MS) because it introduces a novel approach compared to standard treatments like disease-modifying therapies and immunosuppressants. AIH involves exposing patients to short bursts of low oxygen levels, which could stimulate the body's natural repair processes and enhance neural plasticity. Unlike existing treatments that primarily focus on slowing disease progression, AIH has the potential to improve nerve function and repair, offering a promising new avenue for managing MS symptoms.

What evidence suggests that Acute Intermittent Hypoxia is effective for improving arm function in multiple sclerosis?

Research has shown that a treatment called Acute Intermittent Hypoxia (AIH) might benefit people with multiple sclerosis (MS). AIH involves breathing in low oxygen for short periods. Studies have found that this can strengthen ankles in people with MS. Early results also suggest that AIH can help the brain adapt and improve, potentially leading to better movement. Additionally, AIH has improved strength and function in the arms, particularly on the more affected side of the body. In this trial, participants will be assigned to different groups to receive either AIH first or Sham AIH first, with sessions separated by washout periods. Overall, while research is ongoing, these early findings are promising for those with MS seeking to enhance their physical abilities. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Multiple Sclerosis (MS) who are interested in a breathing intervention that may improve arm and hand function. Specific eligibility criteria details were not provided, so participants should inquire further to determine if they qualify.

Inclusion Criteria

I have been free from cancer relapse for at least 6 months.

I was diagnosed with relapsing-remitting MS more than 5 years ago.

I can walk with assistance.

Exclusion Criteria

Modified Ashworth Scale score >3 on elbow joint

Pregnancy as confirmed by urine test

I have a condition that affects the use of my arms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 2 sessions of AIH or Sham AIH, each separated by a 1-week washout period

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for changes in neural pathways and arm function after the intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acute Intermittent Hypoxia

Trial Overview The study tests the effects of Acute Intermittent Hypoxia (AIH), which involves breathing low oxygen levels briefly, on neural pathways and arm function in MS patients. It compares AIH with a sham procedure to assess changes in muscle response and brain signals.

How Is the Trial Designed?

Group I: Sham First Experimental Treatment 2 Interventions

Participants in the this arm will undergo 2 sessions of Sham AIH each separated by a 1-week washout period. 1 week later, participants will undergo 2 sessions of AIH also separated by a 1-week washout period.

Group II: AIH first Experimental Treatment 2 Interventions

Participants in the first arm will undergo 2 sessions of AIH each separated by a 1-week washout period. 1 week later, participants will undergo 2 sessions of Sham AIH also separated by a 1-week washout period.

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

National Multiple Sclerosis Society

Collaborator

Trials

100

Recruited

10,600+

Published Research Related to This Trial

The study found that individuals with the APOE 4 genotype showed lower diaphragm motor-evoked potential (MEP) enhancements in response to acute intermittent hypercapnic-hypoxia (AIHH), indicating that genetic factors can influence the effectiveness of this rehabilitation strategy.

Additionally, the research revealed that males had a greater enhancement in diaphragm MEP compared to females, and that age negatively affected respiratory motor plasticity, highlighting the importance of biological factors in individual responses to AIHH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia. Nair, J., Welch, JF., Marciante, AB., et al.[2023]

Intermittent hypoxia (IH) in a rat model led to increased inflammation in the liver and a significant decrease in the expression of cytochrome P450 enzymes, which are crucial for drug metabolism.

The study highlights the potential risk for patients with obstructive sleep apnea (OSA) who are on medications metabolized by the liver, as IH may impair liver function and drug processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia. Shi, LX., Wang, X., Wu, Q., et al.[2021]

Intermittent hypobaric hypoxia (IHH) effectively protects the brain from injury caused by acute severe hypoxia (ASH) in rats, as shown by reduced oxidative stress and apoptosis-related damage.

The neuroprotective effects of IHH are linked to the downregulation of NF-κB and an increase in erythropoietin (EPO) levels, suggesting a mechanism that prevents oxidative injury and promotes cell survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Hypobaric Hypoxic Preconditioning Provides Neuroprotection by Increasing Antioxidant Activity, Erythropoietin Expression and Preventing Apoptosis and Astrogliosis in the Brain of Adult Rats Exposed to Acute Severe Hypoxia. Coimbra-Costa, D., Garzón, F., Alva, N., et al.[2021]

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]

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 ...