Intermittent Hypoxia for Multiple Sclerosis

Overseen By Alexander Barry, MS, CCRC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shirley Ryan AbilityLab

Disqualifiers: Epilepsy, COPD, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: 10

Duration: 4 weeks

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment involving short bursts of breathing low oxygen levels, similar to conditions on a tall mountain, to determine if it can strengthen muscles in people with multiple sclerosis (MS). Researchers aim to understand how this treatment, called Acute Intermittent Hypoxia (AIH), affects brain activity and ankle strength in MS patients. The trial includes two groups: one receives the real AIH treatment first, while the other starts with a placebo before switching to the real treatment. Suitable participants have relapsing forms of MS, have been stable without relapses for at least a year, and face daily challenges like muscle weakness. As an unphased trial, this study provides a unique opportunity to explore a novel treatment approach for MS symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using dalfampridine, you must have been on the same daily dose for at least 2 months before joining the study.

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

Research has shown that Acute Intermittent Hypoxia (AIH), involving short periods of breathing air with reduced oxygen, is generally safe for people with multiple sclerosis (MS). Studies have found that participants handled AIH sessions well and did not experience major side effects. The treatment did not harm cognitive abilities or brain blood flow. Instead, it improved muscle strength and supported nerve health. Participants in these studies completed the entire program without issues. Overall, AIH appears to be a well-tolerated option for those with MS, offering potential benefits without serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Acute Intermittent Hypoxia (AIH) for treating Multiple Sclerosis (MS) because it introduces a novel approach compared to existing treatments. Unlike current options, such as disease-modifying therapies that target the immune system, AIH uses short bursts of low oxygen levels to potentially enhance neural repair and improve motor function. This method is non-invasive and focuses on promoting the body's natural repair mechanisms, offering a new angle in MS management that could complement or enhance existing therapies.

What evidence suggests that Acute Intermittent Hypoxia might be an effective treatment for multiple sclerosis?

This trial will compare the effects of Acute Intermittent Hypoxia (AIH) with Sham-Acute Intermittent Hypoxia in people with multiple sclerosis (MS). Research has shown that AIH can help people with MS become stronger. Studies have found that AIH is safe and can increase ankle strength in those with MS. AIH appears to enhance the brain's ability to adapt and form new connections, potentially improving movement and thinking skills. It might also repair nerve damage by enhancing the protective layer around nerve fibers. These findings suggest AIH could be a promising treatment for people with MS. ^{1 2 5 6 7}

Who Is on the Research Team?

Milap Sandhu, Pt, PhD

Principal Investigator

Shirley Ryan AbilityLab

Are You a Good Fit for This Trial?

This trial is for people with multiple sclerosis (MS) who are interested in a novel intervention that involves breathing low levels of oxygen intermittently, similar to the air on a tall mountain. The study will explore how this affects brain activation and ankle strength.

Inclusion Criteria

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

My motor function is moderately impaired.

My disability level is moderate to severe but I can still walk.

Exclusion Criteria

Uncontrolled hypertension (Systolic between 85 and 140, diastolic between 90 and 55)

Active contrast-enhancing MS lesions, or diffusion positive lesions suggestive of acute cerebrovascular disease on baseline MRI scan

History of epilepsy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 5 days of Acute Intermittent Hypoxia (AIH) or Sham-AIH interventions, followed by a 2-week washout period, and then another 5 days of the alternate intervention

4 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of neural activations and motor performance

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acute Intermittent Hypoxia
• Sham-Acute Intermittent Hypoxia

Trial Overview The study is testing Acute Intermittent Hypoxia (AIH), where participants breathe short bursts of low-oxygen air. It compares AIH's effects on brain function and muscle strength against a sham procedure (a fake treatment that mimics AIH without using actual low oxygen).

How Is the Trial Designed?

Group I: Sham First Experimental Treatment 2 Interventions

Participants in the Sham First arm will undergo 5 days of Sham-Acute Intermittent Hypoxia Interventions. Following the 5 Days of Sham-AIH, after a 2-week washout period, this group will then undergo 5 days of AIH Interventions. The procedures are identical to Sham-AIH but with 9-10% oxygen for the first breath cycle

Group II: AIH First Experimental Treatment 2 Interventions

Participants in the AIH First arm will undergo 5 days of Acute Intermittent Hypoxia Interventions. Following the 5 Days of AIH, after a 2-week washout period, this group will then undergo 5 days of Sham AIH Interventions. The procedures are identical to AIH but with 21% oxygen for both breath cycles

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+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

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]

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]

A 7-day intermittent hypoxia (IH) protocol with 60-minute daily exposures significantly increased the hypoxic ventilatory response (HVR) by 67%, while a protocol with shorter, multiple bouts increased HVR by 49%, indicating both methods can enhance breathing responses to low oxygen levels.

The longer duration intermittent hypoxia (LDIH) also significantly improved the hypercapnic ventilatory response (HCVR) by 44.1%, which remained elevated for a week after the protocol, while the shorter duration intermittent hypoxia (SDIH) showed smaller, non-significant improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of two different intermittent hypoxia protocols on ventilatory responses to hypoxia and carbon dioxide at rest. Koehle, M., Sheel, W., Milsom, W., et al.[2016]

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]

In a study of 17 healthy adults, it was found that individuals with the APOE4 genotype showed lower respiratory motor plasticity in response to acute intermittent hypercapnic-hypoxia (AIHH), suggesting genetic factors can influence the effectiveness of this rehabilitation strategy.

Additionally, males demonstrated greater improvements in diaphragm motor function compared to females, and older age was associated with reduced respiratory response, highlighting the importance of sex and age as biological determinants in AIHH outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

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 ...