Effects of Acute Intermittent Hypoxia on Neuroplasticity in MS

Multiple Sclerosis Clinical Trial

Official title:

Investigating the Effects of Acute Intermittent Hypoxia on Neuroplasticity in Persons With Multiple Sclerosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06390930
• Other study ID #: STU00221436
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2024
• Est. completion date: July 2027

Study information

• Verified date: April 2024
• Source: Shirley Ryan AbilityLab
• Contact: rachel Kravitt, OTD, OTR/L
• Phone: 3122383947
• Email: rkravitt[@]sralab.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 22
• Est. completion date: July 2027
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypoxia
• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Relapsing-Remitting
• Multiple Sclerosis, Secondary Progressive
• Sclerosis

Intervention

Other:
• Acute Intermittent Hypoxia
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 Hypoxia
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.

Locations

Country	Name	City	State
United States	Shirley Ryan AbilityLab	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Shirley Ryan AbilityLab	National Multiple Sclerosis Society

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Immediately before, immediately after, and 60 minutes after the intervention.
Primary	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.	Immediately before the intervention and immediately after the intervention.
Primary	Threshold For Detecting Passive Joint Movement	An assisted movement with enhanced sensation (AMES) will be used to rotate the participant's joint. The difference between the reference and matching joint angles is used to measure joint position sense. The investigators will present three target positions, and subjects will perform ipsilateral matching for each target 5 times.	Immediately before the intervention and immediately after the intervention.
Primary	Accuracy of Direction Estimation of Passive Joint Movement	An AMES will be used to rotate the participant's joint. The difference between the reference and matching joint angles is used to measure joint position sense. The investigators will present three target positions, and subjects will perform ipsilateral matching for each target 5 times.	Immediately before the intervention and immediately after the intervention.
Secondary	Grip Strength	The participant will squeeze a calibrated dynamometer to measure grip strength.	Immediately before the intervention and immediately after the intervention.
Secondary	Pinch Strength	The participant will pinch a calibrated pinch gauge to measure pinch strength.	Immediately before the intervention and immediately after the intervention.
Secondary	Index Finger Abduction Force	Index finger abduction force will be measured using a load cell. We will also record surface EMG activity from the FDI muscle.	Immediately before the intervention and immediately after the intervention.
Secondary	Nine-Hole Peg Test	A dexterity measurement involving placing 9 pegs in corresponding holes. Time to complete is measured.	Immediately before the intervention and immediately after the intervention.
Secondary	Symbol Digit Modalities Test	A cognition assessment. Using a key, the participant has 90 seconds to match numbers to given geometric figures.	Immediately before the intervention and immediately after the intervention.
Secondary	Box and Block Test	A 60 second dexterity measurement involving translating small wooden blocks from one box to another box separated by a partition.	Immediately before the intervention and immediately after the intervention.
Secondary	Modified Ashworth Scale	A grading system is applied to the amount of tone felt during a rapid high velocity stretch. The minimal value is 0, and the maximum value is 4. A higher score indicates a higher degree of spasticity.	Immediately before the intervention and immediately after the intervention.
Secondary	Ipsilateral Joint Position Matching Task	The participant's hand will be passively moved to a target joint position and then returned to a base position. Participants are then asked to recreate the target joint angle with the same hand. The difference between the reference and matching joint angles is used to measure joint position sense.	Immediately before the intervention and immediately after the intervention.
Secondary	Visual Analog Pain Scale	This is used to measure any changes in pain. It is a one-dimensional scale where the patient marks their pain on a 10-cm ruler. The minimal value is 0, and the maximum value is 10. The higher the score, the greater the pain is.	Immediately before the intervention and immediately after the intervention.