Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS

Shirley Ryan AbilityLab

Status: Not yet enrolling

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

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06390930

STU00221436

Details and patient eligibility

About

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.

Full 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).

Enrollment: 22 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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22 participants in 2 patient groups

AIH first

Experimental group

Description:

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.

Treatment:

Other: Sham Acute Intermittent Hypoxia

Other: Acute Intermittent Hypoxia

Sham First

Experimental group

Description:

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.

Treatment:

Other: Sham Acute Intermittent Hypoxia

Other: Acute Intermittent Hypoxia