Clinical trial NCT06390930: Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS
Official title: Investigating the Effects of Acute Intermittent Hypoxia on Neuroplasticity in Persons With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
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
Lead sponsor: Shirley Ryan AbilityLab
Sponsor class: OTHER
Collaborators: name: National Multiple Sclerosis Society
First posted: 2024-04-30
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: randomized, blinded, placebo-controlled, cross-over with repeated measures
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Motor Evoked Potentials (MEPs) in First Dorsal Interosseous (FDI)
timeFrame: Immediately before, immediately after, and 60 minutes after the intervention.
measure: Changes in Spinal Reflex Threshold
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Threshold For Detecting Passive Joint Movement
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Accuracy of Direction Estimation of Passive Joint Movement
timeFrame: Immediately before the intervention and immediately after the intervention.
Secondary outcomes:
measure: Grip Strength
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Pinch Strength
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Index Finger Abduction Force
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Nine-Hole Peg Test
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Symbol Digit Modalities Test
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Box and Block Test
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Modified Ashworth Scale
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Ipsilateral Joint Position Matching Task
timeFrame: Immediately before the intervention and immediately after the intervention.
measure: Visual Analog Pain Scale
timeFrame: Immediately before the intervention and immediately after the intervention.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Shirley Ryan AbilityLab
state: Illinois
Study officials:
References: