Intermittent Hypoxia in Persons With Multiple Sclerosis

NCT ID: NCT06276634

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-30
• Study Completion Date: 2027-01-31

Brief Summary

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.

Detailed Description

Recent research has shown that AIH, characterized by brief episodes of reduced oxygen levels in the inspired air, has the potential to induce neural adaptations. These adaptations are suspected to influence several aspects of neuroplasticity, including the modulation of neurotransmitters and neurotrophic factors. Persons with MS typically exhibit greater cortical activation to achieve a given motor task compared to healthy controls, suggesting compensatory activations in motor cortices and the recruitment of additional non-motor regions for successful motor control. Therefore, interventions that promote adaptive neuroplasticity in motor control systems may induce a reduction in fMRI activation during motor tasks as well as an increase in functional connectivity between somatomotor cortices. This study will explore potential mechanisms of this intervention in MS using motor task performance and advanced neuroimaging techniques.

Conditions

Multiple Sclerosis; Multiple Sclerosis-Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

AIH First

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

Group Type: EXPERIMENTAL

Acute Intermittent Hypoxia

Intervention Type: OTHER

During each AIH session, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The AIH intervention involves alternating breathing cycles: one with lower oxygen concentration (9-10% Oxygen) than that at sea level (\~21% Oxygen) lasting between 30 and 60 seconds, followed by a similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.

Sham-Acute Intermittent Hypoxia

Intervention Type: OTHER

During each Sham-AIH session, the participant will be equipped with a non-rebreathing face mask, and provided with the Sham-AIH intervention. The Sham-AIH intervention involves alternating breathing cycles: both with oxygen concentrations of \~21% Oxygen lasting between 30 and 60 seconds, followed by another similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.

Sham First

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 Type: EXPERIMENTAL

Acute Intermittent Hypoxia

Intervention Type: OTHER

During each AIH session, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The AIH intervention involves alternating breathing cycles: one with lower oxygen concentration (9-10% Oxygen) than that at sea level (\~21% Oxygen) lasting between 30 and 60 seconds, followed by a similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.

Sham-Acute Intermittent Hypoxia

Intervention Type: OTHER

During each Sham-AIH session, the participant will be equipped with a non-rebreathing face mask, and provided with the Sham-AIH intervention. The Sham-AIH intervention involves alternating breathing cycles: both with oxygen concentrations of \~21% Oxygen lasting between 30 and 60 seconds, followed by another similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.

Interventions

Acute Intermittent Hypoxia

During each AIH session, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The AIH intervention involves alternating breathing cycles: one with lower oxygen concentration (9-10% Oxygen) than that at sea level (\~21% Oxygen) lasting between 30 and 60 seconds, followed by a similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.

Intervention Type: OTHER

Sham-Acute Intermittent Hypoxia

During each Sham-AIH session, the participant will be equipped with a non-rebreathing face mask, and provided with the Sham-AIH intervention. The Sham-AIH intervention involves alternating breathing cycles: both with oxygen concentrations of \~21% Oxygen lasting between 30 and 60 seconds, followed by another similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.

Intervention Type: OTHER

Other Intervention Names

AIH

Eligibility Criteria

Inclusion Criteria

• Diagnoses of relapsing form of MS (including relapsing-remitting MS and secondary-progressive MS)
• Expanded Disability Status Scale (EDSS) score of at least 3 and no more than 6.5
• Motor Functional System Scale (FSS) between 2-4
• Relapse free for at least 1 year
• Age ≥ 18 years and ≤ 75 years
• Safe to be scanned based on MRI questionnaire
• Participants using dalfampridine will be eligible if taking the same daily dose for at least 2 months prior to screening

Exclusion Criteria

• Active contrast-enhancing MS lesions, or diffusion positive lesions suggestive of acute cerebrovascular disease on baseline MRI scan
• Uncontrolled hypertension (Systolic between 85 and 140, diastolic between 90 and 55)
• History of epilepsy
• Chronic obstructive pulmonary disease
• Uncontrolled Sleep apnea
• Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

Shirley Ryan AbilityLab

OTHER

Sponsor Role: lead

Responsible Party

Milap Sandhu

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Milap Sandhu, Pt, PhD

Role: PRINCIPAL_INVESTIGATOR

Shirley Ryan AbilityLab

Locations

Shirley Ryan AbilityLab

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Alexander Barry, MS, CCRC

Role: CONTACT

abarry@sralab.org

3122381435

Facility Contacts

Alexander Barry, MS, CCRC

Role: primary

abarry@sralab.org

3122381435

Other Identifiers

R21HD108587

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU00219535

Identifier Type: -

Identifier Source: org_study_id