Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS

NCT06390930 | Recruiting

• 1 other identifier: STU00221436
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

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

Keywords

multiple sclerosis; plasticity; neuroplasticity; motoneuron; aih; hypoxia; Acute Intermittent Hypoxia; arm; upper extremity

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Immediately before the intervention and immediately after the intervention.

Secondary Outcomes (9)

• Grip Strength

  Immediately before the intervention and immediately after the intervention.

• Pinch Strength

  Immediately before the intervention and immediately after the intervention.

• Index Finger Abduction Force

  Immediately before the intervention and immediately after the intervention.

• Nine-Hole Peg Test

  Immediately before the intervention and immediately after the intervention.

• Symbol Digit Modalities Test

  Immediately before the intervention and immediately after the intervention.

Study Arms (2)

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.

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.

Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia

Interventions

Acute Intermittent Hypoxia OTHER

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.

Also known as: AIH

AIH first; Sham First

Sham Acute Intermittent Hypoxia OTHER

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.

Also known as: Sham AIH

AIH first; Sham First

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Multiple Sclerosis Society: collaborator
• Shirley Ryan AbilityLab: lead

Study Sites (1)

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Hypoxia

Interventions

Insemination, Artificial, Homologous

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Insemination, Artificial; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques; Insemination; Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Milap Sandhu

  Shirley Ryan Ability Lab

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Kalvakota, OTD, OTR/L

CONTACT

3122383947; rkalvakota@sralab.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: randomized, blinded, placebo-controlled, cross-over with repeated measures

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 30, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)