Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS

N/ANot Yet RecruitingNCT06390930

Shirley Ryan AbilityLab22 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Interventions

Acute Intermittent HypoxiaOTHER

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

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Outcomes

Primary Outcomes

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.

Time frame: 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.