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

22 Participants Needed

Trial Summary

What is the purpose of this trial?

This study seeks to explore changes in the neural pathways and arm function following a breathing intervention in the multiple sclerosis (MS) population. The breathing intervention, known as Acute Intermittent Hypoxia (AIH), involves breathing brief bouts of low levels of oxygen. Research has found AIH to be a safe and effective intervention resulting in increased ankle strength in people with MS. Here, the study examines arm and hand function before and after AIH. In order to better understand the brain and spinal cord response to AIH, the investigators will measure muscle response, and signals sent from the brain to the arm muscles before and after AIH.

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 data supports the effectiveness of the treatment Acute Intermittent Hypoxia for Multiple Sclerosis?

Research shows that acute intermittent hypoxia (AIH) can improve nerve repair and reduce inflammation in a mouse model of Multiple Sclerosis (MS), suggesting it may help repair the nervous system and alter the disease course in MS. ^{1 2 3 4 5}

How does the treatment Acute Intermittent Hypoxia (AIH) for multiple sclerosis differ from other treatments?

Acute Intermittent Hypoxia (AIH) is unique because it involves controlled exposure to low oxygen levels for short periods, which may stimulate the body's adaptive responses, unlike traditional treatments that often focus on reducing inflammation with drugs like corticosteroids. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. China pubmed.ncbi.nlm.nih.gov

Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia. [2021]

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

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia. [2023]

3. Switzerland 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. [2021]

4. 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]

5. Germany pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Fatigue in multiple sclerosis is not due to sleep apnoea. [2015]

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

Fulminant demyelinating diseases. [2021]

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

Fulminant Demyelinating Diseases of the Central Nervous System. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Characteristics of hypersomnia due to inflammatory demyelinating diseases of the central nervous system. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Sleep disorders and fatigue in multiple sclerosis: evidence for association and interaction. [2015]