Intermittent Hypoxia for Multiple Sclerosis

Recruiting in Palo Alto (17 mi)

Overseen by Milap Sandhu, Pt, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Shirley Ryan AbilityLab

Disqualifiers: Epilepsy, COPD, Uncontrolled hypertension, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study aims to understand the mechanisms of a novel intervention involving breathing short durations of low levels of oxygen for persons with multiple sclerosis (MS). This intervention with low levels of oxygen is called Acute Intermittent Hypoxia (AIH), the levels of oxygen experienced are similar to breathing the air on a tall mountain, for less than 1 minute at a time. Previous studies have shown that AIH is a safe and effective way to increase strength in persons with MS. Here the investigators aim to look at brain activation and ankle strength before and after AIH to gain a better understanding of how the AIH may improve strength in those persons with MS.

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 data supports the effectiveness of the treatment 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 is the treatment Acute Intermittent Hypoxia (AIH) unique for Multiple Sclerosis (MS)?

Acute Intermittent Hypoxia (AIH) is a novel, non-invasive treatment that involves brief periods of breathing low-oxygen air, which can enhance the body's ability to repair nerve damage and reduce inflammation in Multiple Sclerosis (MS). Unlike other treatments, AIH promotes remyelination (repair of nerve coverings) and alters the disease course by improving functional recovery and reducing inflammation. ^{1 2 5 6 7}

Research Team

Milap Sandhu, Pt, PhD

Principal Investigator

Shirley Ryan AbilityLab

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Acute Intermittent Hypoxia (Behavioural Intervention)
• Sham-Acute Intermittent Hypoxia (Other)

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).

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Shirley Ryan AbilityLab Chicago, IL

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Patients Recruited

17,900+

Northwestern University

Collaborator

Trials

1674

Patients Recruited

989,000+

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

Collaborator

Trials

2103

Patients Recruited

2,760,000+

References

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

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia. [2023] Acute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials report considerable inter-individual response variability.

2. 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] Remyelination and neurodegeneration prevention mitigate disability in Multiple Sclerosis (MS). We have shown acute intermittent hypoxia (AIH) is a novel, non-invasive and effective therapy for peripheral nerve repair, including remyelination. Thus, we posited AIH would improve repair following CNS demyelination and address the paucity of MS repair treatments. AIH's capacity to enhance intrinsic repair, functional recovery and alter disease course in the experimental autoimmune encephalomyelitis (EAE) model of MS was assessed. EAE was induced by MOG35-55 immunization in C57BL/6 female mice. EAE mice received either AIH (10 cycles-5 min 11% oxygen alternating with 5 min 21% oxygen) or Normoxia (control; 21% oxygen for same duration) once daily for 7d beginning at near peak EAE disease score of 2.5. Mice were followed post-treatment for an additional 7d before assessing histopathology or 14d to examine maintenance of AIH effects. Alterations in histopathological correlates of multiple repair indices were analyzed quantitatively in focally demyelinated ventral lumbar spinal cord areas to assess AIH impacts. AIH begun at near peak disease significantly improved daily clinical scores/functional recovery and associated histopathology relative to Normoxia controls and the former were maintained for at least 14d post-treatment. AIH enhanced correlates of myelination, axon protection and oligodendrocyte precursor cell recruitment to demyelinated areas. AIH also effected a dramatic reduction in inflammation, while polarizing remaining macrophages/microglia toward a pro-repair state. Collectively, this supports a role for AIH as a novel non-invasive therapy to enhance CNS repair and alter disease course following demyelination and holds promise as a neuroregenerative MS strategy.

3. China pubmed.ncbi.nlm.nih.gov

Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia. [2021] Intermittent hypoxia (IH) is a key element of obstructive sleep apnea (OSA) that can lead to disorders in the liver. In this study, IH was established in a rat model to examine its effects on the expression of hepatic cytochrome P450 (CYP) and CYP regulators, including nuclear receptors.

4. 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] Exposure to intermittent hypoxia has been demonstrated to be an efficient tool for hypoxic preconditioning, preventing damage to cells and demonstrating therapeutic benefits. We aimed to evaluate the effects of respiratory intermittent hypobaric hypoxia (IHH) to avoid brain injury caused by exposure to acute severe hypoxia (ASH).

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

Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex. [2022] Acute intermittent hypoxia (AIH) is a safe and non-invasive treatment approach that uses brief, repetitive periods of breathing reduced oxygen air alternated with normoxia. While AIH is known to affect spinal circuit excitability, the effects of AIH on cortical excitability remain largely unknown. We investigated the effects of AIH on cortical excitability within the primary motor cortex.

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

The effect of two different intermittent hypoxia protocols on ventilatory responses to hypoxia and carbon dioxide at rest. [2016] Intermittent hypoxia (IH) consists of bouts of hypoxic exposure interspersed with normoxic intervals. The optimal IH regime for increasing the ventilatory response in humans is unknown, although in animals there is evidence that multiple short duration bouts of intermittent hypoxia (SDIH) provoke larger changes in chemosensitivity than longer duration bouts of intermittent hypoxia (LDIH). The purpose of this study was to compare responses to both hypercapnia and hypoxia between the two protocols.

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

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia. [2023] Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.