The Synergistic Effects of AIH and FES in Persons With MS

NCT06413602 | Active Not Recruiting

• 1 other identifier: STU00221027
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive

Keywords

multiple sclerosis; plasticity; electrical stimulation; NMES; modalities; neuroplasticity; motoneuron; aih; hypoxia; acute intermittent hypoxia; control; control group

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Ankle Dorsiflexion Torque

  Immediately prior to and within 60 minutes after the intervention.

• Ankle Dorsiflexion EMG

  Immediately prior to and within 60 minutes after the intervention.

• Symbol Digit Modalities Test

  Immediately prior to and within 60 minutes after the intervention.

Study Arms (3)

AIH alone

EXPERIMENTAL

Participants will undergo 30 minutes of AIH.

Other: Acute Intermittent Hypoxia

NMES alone

EXPERIMENTAL

Participants will undergo repetitive common peroneal nerve stimulation for up to 30 minutes.

Other: Neuromuscular Electrical Stimulation

Combined AIH and NMES

EXPERIMENTAL

Participants will undergo 30 minutes of AIH. Immediately following, participants will undergo NMES for up to 30 minutes.

Other: Acute Intermittent Hypoxia; Other: Neuromuscular Electrical Stimulation

Interventions

Acute Intermittent Hypoxia OTHER

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.

Also known as: AIH

AIH alone; Combined AIH and NMES

Neuromuscular Electrical Stimulation OTHER

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.

Also known as: NMES

Combined AIH and NMES; NMES alone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of relapsing form of MS
• Expanded Disability Status Scale (EDSS) score of at least 3 and no more than 6.5
• Relapse free for at least 1 year
• Age ≥18 years and ≤75 years
• No change in Dalfampridine dose at least 2 months prior to enrollment

You may not qualify if:

• Uncontrolled hypertension or hypotension (outside 140/90 and 90/60 mmHg)
• History of epilepsy or seizures
• Age ≥18 years and ≤75 years
• Safe to participate in TMS (TMS questionnaire)
• 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)
• History of seizures or epilepsy diagnosis
• 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

Sponsors & Collaborators

• Northwestern University: collaborator
• Shirley Ryan AbilityLab: lead

Study Sites (1)

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Hypoxia

Interventions

Insemination, Artificial, Homologous

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Insemination, Artificial; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques; Insemination; Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: randomized, blinded, cross-over study

Study Record Dates

• First Submitted: May 9, 2024
• First Posted: May 14, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)