The Synergistic Effects of AIH and FES in Persons With MS

May 9, 2024 updated by: Milap Sandhu, Shirley Ryan AbilityLab

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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, we 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. We will conduct a randomized, blinded, placebo-controlled, cross-over study in 20 MS patients with established motor deficits and controlled relapse activity.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Shirley Ryan AbilityLab

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AIH alone
Participants will undergo 30 minutes of AIH.
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.
Other Names:
  • AIH
Experimental: NMES alone
Participants will undergo repetitive common peroneal nerve stimulation for up to 30 minutes.
Other: 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.
Other Names:
  • NMES
Experimental: Combined AIH and NMES
Participants will undergo 30 minutes of AIH. Immediately following, participants will undergo NMES for up to 30 minutes.
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.
Other Names:
  • AIH
Other: 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.
Other Names:
  • NMES

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Motor Evoked Potentials (MEPs) in Ankle Dorsiflexors
Time Frame: Immediately prior to and within 60 minutes after the intervention.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ankle Dorsiflexion Torque
Time Frame: Immediately prior to and within 60 minutes after the intervention.
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.
Ankle Dorsiflexion EMG
Time Frame: Immediately prior to and within 60 minutes after the intervention.
While measuring ankle dorsiflexion torque, we will also record surface electromyography (EMG) from the tibialis anterior muscle during each contraction.
Immediately prior to and within 60 minutes after the intervention.
Symbol Digit Modalities Test
Time Frame: Immediately prior to and within 60 minutes after the intervention.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shirley Ryan AbilityLab

Collaborators

Northwestern University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2024

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

May 9, 2024

First Submitted That Met QC Criteria

May 9, 2024

First Posted (Actual)

May 14, 2024

Study Record Updates

Last Update Posted (Actual)

May 14, 2024

Last Update Submitted That Met QC Criteria

May 9, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00221027

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We do not currently have a plan to share IPD.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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