Multiple SclerosisNCT06390930
Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS
A study testing Acute Intermittent Hypoxia in people with Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, run by Shirley Ryan AbilityLab at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
- What is being tested?
- Acute Intermittent Hypoxia
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2025to Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of relapsing-remitting MS according to the McDonald criteria, over 5 years ago
- Relapse free for at least 6 months
- Expanded Disability Status Scale (EDSS) ≤7
- Index finger abduction strength <5 according to Medical Research Council Scale, or 9-Hole Peg Test score >20 seconds in at least one hand
- Stable disease modifying therapies for at least 6 months
- Individuals taking dalfampridine will be eligible if taking the same daily dose for at least 2 months prior to screening
Who cannot join
- Another diagnosis (e.g., peripheral neuropathies or orthopedic) affecting upper limb function
- Mini-Mental State Examination (MMSE) score <24
- Modified Ashworth Scale score >3 on elbow joint
- Uncontrolled hypertension or hypotension (outside 140/90 and 85/55 mmHg)
- History of epilepsy, chronic obstructive pulmonary disease, or sleep apnea
- Unstable medical conditions, ongoing upper limb therapy, or musculoskeletal pain
- Pregnancy as confirmed by urine test
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Shirley Ryan AbilityLab
Chicago, Illinois, 60611
Rachel Kravitt, OTD, OTR/L, (312)238-3947, rkravitt@sralab.org
Milap Sandhu, PT, PhD
About this study
Official title: Investigating the Effects of Acute Intermittent Hypoxia on Neuroplasticity in Persons With Multiple Sclerosis
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.
Read the detailed description
While AIH has shown potential in enhancing neuroplasticity in people with spinal cord injury (SCI), it has yet to be studied extensively in MS. Preliminary research in the MS population demonstrates that a single session of AIH enhances motor output, increasing voluntary muscle strength by as much as 15-20% within 60 minutes. This study will explore potential mechanisms of AIH in MS using measurements of arm function, as well as examination of corticospinal and spinal motoneuron excitability.
Over the past decade, studies have found that brief episodes of modest oxygen reduction (termed AIH) can rapidly enhance neural plasticity in persons with incomplete SCI. AIH activates the serotonergic pathway, leading to increased activity of serotonin receptors and the synthesis of plasticity-related proteins. This plasticity is manifested by a rapid increase in voluntary muscle strength, emerging within 60-90 minutes, in both lower- and upper-limb muscles. The actions of AIH appear to be biologically linked to systems designed to preserve breathing systems that are impaired by damage to the central nervous system (CNS).
- Conditions
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
- Being tested
- Acute Intermittent Hypoxia, Sham Acute Intermittent Hypoxia
- Keywords
- multiple sclerosis, plasticity, neuroplasticity, motoneuron, aih, hypoxia, Acute Intermittent Hypoxia, arm, upper extremity
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute Intermittent HypoxiaOther
Also called AIH
During AIH, 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 cycle involves breathing air with lower oxygen concentration (9-10% oxygen) for 30 and 90 seconds, followed by breathing normal room air (21% oxygen) for a similar duration. This cycle is repeated 15 times in one session. Blood oxygen and heart rate are monitored throughout.
Sham Acute Intermittent HypoxiaOther
Also called Sham AIH
During Sham AIH, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The Sham AIH intervention involves alternating breathing cycles. One cycle involves breathing air closely resembling room air (~21% oxygen) for 30 and 90 seconds, followed by breathing normal room air (21% oxygen) for a similar duration. This cycle is repeated 15 times in one session. Blood oxygen and heart rate are monitored throughout.
| Study group | Role | What they receive |
|---|---|---|
| AIH first | Experimental | 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. Receives: Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia |
| Sham First | Experimental | 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. Receives: Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motor Evoked Potentials (MEPs) in First Dorsal Interosseous (FDI)
The MEPs will be elicited by Transcranial Magnetic Stimulation (TMS), a procedure that uses magnetic fields to stimulate nerve cells in the brain.
Measured: Immediately before, immediately after, and 60 minutes after the intervention.
Changes in Spinal Reflex Threshold
Spinal reflect threshold will be measured by calculating the average change in threshold length recorded from the biceps tendon's indentation. A linear motor will be used to impose precise tendon indentations of the biceps brachii.
Measured: Immediately before the intervention and immediately after the intervention.
Threshold For Detecting Passive Joint Movement
An assisted movement with enhanced sensation (AMES) will be used to rotate the participant's joint. The difference between the reference and matching joint angles is used to measure joint position sense. The investigators will present three target positions, and subjects will perform ipsilateral matching for each target 5 times.
Measured: Immediately before the intervention and immediately after the intervention.
Accuracy of Direction Estimation of Passive Joint Movement
An AMES will be used to rotate the participant's joint. The difference between the reference and matching joint angles is used to measure joint position sense. The investigators will present three target positions, and subjects will perform ipsilateral matching for each target 5 times.
Measured: Immediately before the intervention and immediately after the intervention.
Secondary outcomes (9)
Grip Strength
The participant will squeeze a calibrated dynamometer to measure grip strength.
Measured: Immediately before the intervention and immediately after the intervention.
Pinch Strength
The participant will pinch a calibrated pinch gauge to measure pinch strength.
Measured: Immediately before the intervention and immediately after the intervention.
Index Finger Abduction Force
Index finger abduction force will be measured using a load cell. We will also record surface EMG activity from the FDI muscle.
Measured: Immediately before the intervention and immediately after the intervention.
Nine-Hole Peg Test
A dexterity measurement involving placing 9 pegs in corresponding holes. Time to complete is measured.
Measured: Immediately before the intervention and immediately after the intervention.
Symbol Digit Modalities Test
A cognition assessment. Using a key, the participant has 90 seconds to match numbers to given geometric figures.
Measured: Immediately before the intervention and immediately after the intervention.
Box and Block Test
A 60 second dexterity measurement involving translating small wooden blocks from one box to another box separated by a partition.
Measured: Immediately before the intervention and immediately after the intervention.
Modified Ashworth Scale
A grading system is applied to the amount of tone felt during a rapid high velocity stretch. The minimal value is 0, and the maximum value is 4. A higher score indicates a higher degree of spasticity.
Measured: Immediately before the intervention and immediately after the intervention.
Ipsilateral Joint Position Matching Task
The participant's hand will be passively moved to a target joint position and then returned to a base position. Participants are then asked to recreate the target joint angle with the same hand. The difference between the reference and matching joint angles is used to measure joint position sense.
Measured: Immediately before the intervention and immediately after the intervention.
Visual Analog Pain Scale
This is used to measure any changes in pain. It is a one-dimensional scale where the patient marks their pain on a 10-cm ruler. The minimal value is 0, and the maximum value is 10. The higher the score, the greater the pain is.
Measured: Immediately before the intervention and immediately after the intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2024
- Study start1 Feb 2025
- Primary completionJul 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Shirley Ryan AbilityLabThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- randomized, blinded, placebo-controlled, cross-over with repeated measures
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shirley Ryan AbilityLab
- Sponsor type
- University, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Responsible party
- Principal investigator, Milap Sandhu, Shirley Ryan AbilityLab
- Investigators
- Milap Sandhu, Principal investigator, Shirley Ryan Ability Lab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06390930
- Sponsor's protocol ID
- STU00221436
- Status last verified
- Feb 2026
- First submitted
- 24 Apr 2024
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We do not currently have a plan to share IPD.
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Effects of Acute Intermittent Hypoxia on Neuroplasticity in Persons With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT06390930
- Acronym / sponsor ID
- STU00221436
- Conditions
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
- Keywords
- multiple sclerosis, plasticity, neuroplasticity, motoneuron, aih, hypoxia, Acute Intermittent Hypoxia, arm
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Shirley Ryan AbilityLabUniversity, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Study start
- 1 Feb 2025 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 30 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
While AIH has shown potential in enhancing neuroplasticity in people with spinal cord injury (SCI), it has yet to be studied extensively in MS. Preliminary research in the MS population demonstrates that a single session of AIH enhances motor output, increasing voluntary muscle strength by as much as 15-20% within 60 minutes. This study will explore potential mechanisms of AIH in MS using measurements of arm function, as well as examination of corticospinal and spinal motoneuron excitability.
Over the past decade, studies have found that brief episodes of modest oxygen reduction (termed AIH) can rapidly enhance neural plasticity in persons with incomplete SCI. AIH activates the serotonergic pathway, leading to increased activity of serotonin receptors and the synthesis of plasticity-related proteins. This plasticity is manifested by a rapid increase in voluntary muscle strength, emerging within 60-90 minutes, in both lower- and upper-limb muscles. The actions of AIH appear to be biologically linked to systems designed to preserve breathing systems that are impaired by damage to the central nervous system (CNS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- randomized, blinded, placebo-controlled, cross-over with repeated measures
| Arm | Type | Receives |
|---|---|---|
| AIH first | Experimental | Other: Acute Intermittent Hypoxia, Other: Sham Acute Intermittent HypoxiaParticipants 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. |
| Sham First | Experimental | Other: Acute Intermittent Hypoxia, Other: Sham Acute Intermittent HypoxiaParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of relapsing-remitting MS according to the McDonald criteria, over 5 years ago
- Relapse free for at least 6 months
- Expanded Disability Status Scale (EDSS) ≤7
- Index finger abduction strength <5 according to Medical Research Council Scale, or 9-Hole Peg Test score >20 seconds in at least one hand
- Stable disease modifying therapies for at least 6 months
Key exclusion criteria (7 listed)
- Another diagnosis (e.g., peripheral neuropathies or orthopedic) affecting upper limb function
- Mini-Mental State Examination (MMSE) score <24
- Modified Ashworth Scale score >3 on elbow joint
- Uncontrolled hypertension or hypotension (outside 140/90 and 85/55 mmHg)
- History of epilepsy, chronic obstructive pulmonary disease, or sleep apnea
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute Intermittent HypoxiaAlso: AIHDuring AIH, 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 cycle involves breathing air with lower oxygen concentration (9-10% oxygen) for 30 and 90 seconds, followed by breathing normal room air (21% oxygen) for a similar duration. This cycle is repeated 15 times in one session. Blood oxygen and heart rate are monitored throughout. | Other | AIH first, Sham First |
| Sham Acute Intermittent HypoxiaAlso: Sham AIHDuring Sham AIH, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The Sham AIH intervention involves alternating breathing cycles. One cycle involves breathing air closely resembling room air (~21% oxygen) for 30 and 90 seconds, followed by breathing normal room air (21% oxygen) for a similar duration. This cycle is repeated 15 times in one session. Blood oxygen and heart rate are monitored throughout. | Other | AIH first, Sham First |
Primary outcome
Motor Evoked Potentials (MEPs) in First Dorsal Interosseous (FDI)
Time frame: Immediately before, immediately after, and 60 minutes after the intervention.
The MEPs will be elicited by Transcranial Magnetic Stimulation (TMS), a procedure that uses magnetic fields to stimulate nerve cells in the brain.
Changes in Spinal Reflex Threshold
Time frame: Immediately before the intervention and immediately after the intervention.
Spinal reflect threshold will be measured by calculating the average change in threshold length recorded from the biceps tendon's indentation. A linear motor will be used to impose precise tendon indentations of the biceps brachii.
Threshold For Detecting Passive Joint Movement
Time frame: Immediately before the intervention and immediately after the intervention.
An assisted movement with enhanced sensation (AMES) will be used to rotate the participant's joint. The difference between the reference and matching joint angles is used to measure joint position sense. The investigators will present three target positions, and subjects will perform ipsilateral matching for each target 5 times.
Accuracy of Direction Estimation of Passive Joint Movement
Time frame: Immediately before the intervention and immediately after the intervention.
An AMES will be used to rotate the participant's joint. The difference between the reference and matching joint angles is used to measure joint position sense. The investigators will present three target positions, and subjects will perform ipsilateral matching for each target 5 times.
9 secondary outcomes
Grip Strength
Time frame: Immediately before the intervention and immediately after the intervention.
Pinch Strength
Time frame: Immediately before the intervention and immediately after the intervention.
Index Finger Abduction Force
Time frame: Immediately before the intervention and immediately after the intervention.
Nine-Hole Peg Test
Time frame: Immediately before the intervention and immediately after the intervention.
Symbol Digit Modalities Test
Time frame: Immediately before the intervention and immediately after the intervention.
Box and Block Test
Time frame: Immediately before the intervention and immediately after the intervention.
Modified Ashworth Scale
Time frame: Immediately before the intervention and immediately after the intervention.
Ipsilateral Joint Position Matching Task
Time frame: Immediately before the intervention and immediately after the intervention.
Visual Analog Pain Scale
Time frame: Immediately before the intervention and immediately after the intervention.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
- Individual participant dataSharing planned: No. We do not currently have a plan to share IPD.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Milap Sandhu principal investigator
Shirley Ryan Ability Lab
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acute Intermittent Hypoxia in people with Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, run by Shirley Ryan AbilityLab at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rachel Kalvakota, OTD, OTR/L (3122383947, rkalvakota@sralab.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motor Evoked Potentials (MEPs) in First Dorsal Interosseous (FDI) (time frame: Immediately before, immediately after, and 60 minutes after the intervention.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.