The Synergistic Effects of AIH and FES in Persons With MS

Multiple Sclerosis Clinical Trial

Official title:

Exploring the Synergistic Effects of AIH and FES in Persons With MS

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06413602
• Other study ID #: STU00221027
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2024
• Est. completion date: August 2027

Study information

• Verified date: June 2024
• Source: Shirley Ryan AbilityLab
• Contact: Rachel A Kravitt, OTD, OTR/L
• Phone: (312)238-3947
• Email: rkravitt[@]sralab.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine how neuromuscular electrical stimulation (NMES), may synergistically enhance corticospinal excitability in people with relapsing form multiple sclerosis (MS). This is an important intermediate step to evaluate the potential of AIH + NMES as a plasticity-priming strategy for more efficacious interventions for persons with MS. This study will measure ankle torque generation and amplitude of motor evoked potentials (MEPs) using a repeated measures study design in order to better understand the effects of AIH combined with NMES, as compared to only receiving NMES, and only receiving AIH.

Description:

NMES: NMES refers to the application of mild electrical stimulation and is often used as an assistive technology for foot drop in MS and other neurologic conditions. The NMES-induced improvement in motor performance appears to be mediated primarily by an increase in corticomotoneuronal excitability. A single session of NMES applied over a peripheral nerve, has been shown to transiently increase net corticospinal excitability (increased MEP amplitude) in both able-bodied individuals and in people with neurological conditions.

AIH: 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. 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. Over the past decade, studies have found 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 this study, the investigators will examine how NMES, which has been shown to affect cortical excitability, and AIH, which has been shown to affect corticospinal plasticity, may synergistically enhance corticospinal excitability in people with relapsing form of MS. Foot drop is a common symptom in the diagnosis of MS where the inability to maintain active dorsiflexion during the swing phase of the gait cycle affects walking efficiency, instability, and falls. Seminal studies show that individuals with MS retain the ability to express plasticity even at higher levels of disease burden. This indicates that strategies targeting neuroplasticity can be used to enhance functional recovery and limit the impact of MS disability. The investigators will conduct a randomized, blinded, placebo-controlled, cross-over study in 20 MS patients with established motor deficits and controlled relapse activity.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: August 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosis of relapsing form of MS

• Expanded Disability Status Scale (EDSS) score of at least 3 and no more than 6.5

• Motor Functional Systems Score (FSS) between 2-4

• Relapse free for at least 1 year

• Age =18 years and =75 years

• Safe to participate in MRI (as indicated via the SRALab MRI questionnaire)

• No change in Dalfampridine dose at least 2 months prior to enrollment

Exclusion Criteria:

• Uncontrolled hypertension or hypotension (outside 140/90 and 90/60 mmHg)

• History of epilepsy or seizures

• Uncontrolled medical problems affecting the lungs (pulmonary diseases including chronic obstructive pulmonary disease), the heart (cardiovascular diseases) or the musculoskeletal system (orthopedic diseases)

• Premorbid, ongoing major depression or psychosis, altered cognitive status

• History of stroke

• Metal in head (e.g., surgical clips, shrapnel)

• Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants

• Surgery to the head

• Any non-MS related neurological diseases

• Illnesses that may have caused brain injury

• Unexplained frequent or severe headaches

• Pregnancy in females

• Implanted devices (e.g., pacemakers, medical pumps, brain stimulators)

Related Conditions & MeSH terms

• 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.
• Neuromuscular Electrical Stimulation
During NMES, participants will receive electrical stimulation to the common peroneal nerve. Stimulation will be done with a 50% duty cycle, duration of 0.5-1ms for each pulse and a frequency 25-40 Hz. The stimulus intensity will be adjusted to produce approximately 50% of the maximum M-wave (compound muscle action potential) for each participant.

Locations

Country	Name	City	State
United States	Shirley Ryan AbilityLab	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Shirley Ryan AbilityLab	Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Motor Evoked Potentials (MEPs) in Ankle Dorsiflexors	The MEPs will be elicited by Transcranial Magnetic Stimulation (TMS), a procedure that uses magnetic fields to stimulate nerve cells in the brain.	Immediately prior to and within 60 minutes after the intervention.
Secondary	Ankle Dorsiflexion Torque	Maximal volitional ankle dorsiflexion flexion torque will be measured using a strength testing dynamometer (Biodex System 4).	Immediately prior to and within 60 minutes after the intervention.
Secondary	Ankle Dorsiflexion EMG	While measuring ankle dorsiflexion torque, the investigators will also record surface electromyography (EMG) from the tibialis anterior muscle during each contraction. Average peak EMG amplitude will be calculated.	Immediately prior to and within 60 minutes after the intervention.
Secondary	Symbol Digit Modalities Test	A neurocognitive test that requires individuals to pair specific numbers with given geometric figures within 90 seconds. Both written and oral format will be administered, and scores will be calculated by totaling the number of correct answers for each section.	Immediately prior to and within 60 minutes after the intervention.