Intermittent Hypoxia in Persons With Multiple Sclerosis

Not Applicable

Recruiting

• Conditions: Multiple Sclerosis-Relapsing-Remitting; Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive
• Interventions: Other: Acute Intermittent Hypoxia; Other: Sham-Acute Intermittent Hypoxia

• Registration Number: NCT06276634
• Lead Sponsor: Shirley Ryan AbilityLab

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.

Study Timeline

• Study First Submitted: 2023-12-11
• Study First Submitted QC: 2024-02-22
• Study First Posted: 2024-02-26
• Status Verified: 2024-04
• Study Start: 2024-04-30
• Last Update Submitted: 2024-04-30
• Last Update Posted: 2024-05-02
• Primary Completion: 2026-01
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
AIH First	Sham-Acute Intermittent Hypoxia	Participants in the AIH First arm will undergo 5 days of Acute Intermittent Hypoxia Interventions. Following the 5 Days of AIH, after a 2-week washout period, this group will then undergo 5 days of Sham AIH Interventions. The procedures are identical to AIH but with 21% oxygen for both breath cycles
AIH First	Acute Intermittent Hypoxia	Participants in the AIH First arm will undergo 5 days of Acute Intermittent Hypoxia Interventions. Following the 5 Days of AIH, after a 2-week washout period, this group will then undergo 5 days of Sham AIH Interventions. The procedures are identical to AIH but with 21% oxygen for both breath cycles
Sham First	Sham-Acute Intermittent Hypoxia	Participants in the Sham First arm will undergo 5 days of Sham-Acute Intermittent Hypoxia Interventions. Following the 5 Days of Sham-AIH, after a 2-week washout period, this group will then undergo 5 days of AIH Interventions. The procedures are identical to Sham-AIH but with 9-10% oxygen for the first breath cycle
Sham First	Acute Intermittent Hypoxia	Participants in the Sham First arm will undergo 5 days of Sham-Acute Intermittent Hypoxia Interventions. Following the 5 Days of Sham-AIH, after a 2-week washout period, this group will then undergo 5 days of AIH Interventions. The procedures are identical to Sham-AIH but with 9-10% oxygen for the first breath cycle

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Task fMRI	Before and following each 5-day intervention block	This outcome observes neural activations during voluntary muscle activations

Trial Locations

Locations (1)

Shirley Ryan AbilityLab; 🇺🇸 Chicago, Illinois, United States