Multiple Sclerosis, Multiple Sclerosis-Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
Conditions
Keywords
multiple sclerosis, AIH, Hypoxia
Brief summary
This study aims to understand the mechanisms of a novel intervention involving breathing short durations of low levels of oxygen for persons with multiple sclerosis (MS). This intervention with low levels of oxygen is called Acute Intermittent Hypoxia (AIH), the levels of oxygen experienced are similar to breathing the air on a tall mountain, for less than 1 minute at a time. Previous studies have shown that AIH is a safe and effective way to increase strength in persons with MS. Here the investigators aim to look at brain activation and ankle strength before and after AIH to gain a better understanding of how the AIH may improve strength in those persons with MS.
Detailed description
Recent research has shown that AIH, characterized by brief episodes of reduced oxygen levels in the inspired air, has the potential to induce neural adaptations. These adaptations are suspected to influence several aspects of neuroplasticity, including the modulation of neurotransmitters and neurotrophic factors. Persons with MS typically exhibit greater cortical activation to achieve a given motor task compared to healthy controls, suggesting compensatory activations in motor cortices and the recruitment of additional non-motor regions for successful motor control. Therefore, interventions that promote adaptive neuroplasticity in motor control systems may induce a reduction in fMRI activation during motor tasks as well as an increase in functional connectivity between somatomotor cortices. This study will explore potential mechanisms of this intervention in MS using motor task performance and advanced neuroimaging techniques.
Interventions
During each AIH session, 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 with lower oxygen concentration (9-10% Oxygen) than that at sea level (\~21% Oxygen) lasting between 30 and 60 seconds, followed by a similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.
OTHERSham-Acute Intermittent Hypoxia
During each Sham-AIH session, the participant will be equipped with a non-rebreathing face mask, and provided with the Sham-AIH intervention. The Sham-AIH intervention involves alternating breathing cycles: both with oxygen concentrations of \~21% Oxygen lasting between 30 and 60 seconds, followed by another similar duration of normal room air (21% Oxygen). This cycle will be repeated 15 times in one session, continuous blood oxygen levels and heart rate will be monitored.
Sponsors
Shirley Ryan AbilityLab
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Randomized, double-blind, placebo-controlled, cross-over, repeated measures study design
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnoses of relapsing form of MS (including relapsing-remitting MS and secondary-progressive MS) * Expanded Disability Status Scale (EDSS) score of at least 3 and no more than 6.5 * Motor Functional System Scale (FSS) between 2-4 * Relapse free for at least 1 year * Age ≥ 18 years and ≤ 75 years * Safe to be scanned based on MRI questionnaire * Participants using dalfampridine will be eligible if taking the same daily dose for at least 2 months prior to screening
Exclusion criteria
* Active contrast-enhancing MS lesions, or diffusion positive lesions suggestive of acute cerebrovascular disease on baseline MRI scan * Uncontrolled hypertension (Systolic between 85 and 140, diastolic between 90 and 55) * History of epilepsy * Chronic obstructive pulmonary disease * Uncontrolled Sleep apnea * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ankle Plantarflexion Strength | Before and following each 5-day intervention block | Participants will be seated in an adjustable chair with tested foot secured to a foot plate with the ankle in line with a rotational load cell. Participants will be asked to produce maximal ankle plantarflexion contractions, Electromyographic signals of the gastrocnemius, tibialis anterior, and soleus will be recorded simultaneously |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Task fMRI | Before and following each 5-day intervention block | This outcome observes neural activations during voluntary muscle activations |
Countries
United States
Contacts
CONTACTAlexander Barry, MS, CCRC
PRINCIPAL_INVESTIGATORMilap Sandhu, Pt, PhD
Shirley Ryan AbilityLab
Outcome results
None listed