Neurophysiological Effects of Transcutaneous Electrical Nerve Stimulation in Persons With MS

Neurophysiological Effects of Transcutaneous Electrical Nerve Stimulation in Persons With MS - a Pilot Study

Transcutaneous Electrical Nerve Stimulation (TENS) is a treatment that could potentially reduce walking problems and fatigue in persons with Multiple Sclerosis. However, extensive use of TENS in a clinical setting is hindered by a lack of neurophysiological understanding of the effects of TENS. The primary objective of this pilot study is therefore to investigate the effects of TENS on brain activity in pwMS measured with fMRI.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis; Fatigue; Walking, Difficulty
• Intervention / Treatment: Device: Transcutaneous Electrical Nerve Stimulation; Behavioral: Movement

Detailed Description

This study is an exploratory study to see if we can detect changes in fMRI activity during TENS in persons with MS. This is a randomized, single-blind crossover design. Subjects will undergo an MRI scan while they receive sham stimulation of the tibialis anterior, active stimulation of the tibialis anterior, stimulation of the quadriceps, perform continuous movements of the foot (plantar & dorsiflexion) and a combination of stimulation of the tibialis anterior and movement of the foot. This study will include 15 subjects with relapsing remitting or progressive MS and 15 healthy controls. Blood-oxygen-level-dependent (BOLD) activation changes and the interaction networks before, during and after active TENS and differences in activation due to stimulation on quadriceps vs. tibialis anterior, stimulation on tibialis anterior vs plantar/dorsiflexion and stimulation on tibialis anterior vs stimulation combined with plantar/dorsiflexion. This will be compared between pwMS and healthy controls. This study can add to the limited knowledge and possibly help to personalize and implement TENS in the clinic.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nikki Dreijer; Phone Number: 0625647172; Email: n.dreijer@umcg.nl
• Study Contact Backup: Name: Inge Zijdewind; Email: c.a.t.zijdewind@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• age: 18-65 years
• EDSS score < 7

Exclusion Criteria:

• metal or electrical implants
• BMI > 40
• claustrophobia
• being pregnant
• having a psychiatric disorder
• having cognitive or communication problems which reduces the capacity to understand instructions
• having a neurological disorder other than MS
• having cardiac arrhythmia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: sham stimulation of the tibialis anterior	Device: Transcutaneous Electrical Nerve Stimulation; Transcutaneous electrical nerve stimulation (TENS) is a safe, relatively cheap, and non-painful stimulation of the peripheral sensory and motor nerves. The stimulator is easy to operate and pwMS can apply the stimulation themselves at home. This makes TENS an interesting tool to augment sensory input. A high frequency and long pulse duration is used.
Experimental: active stimulation of the tibialis anterior	Device: Transcutaneous Electrical Nerve Stimulation; Transcutaneous electrical nerve stimulation (TENS) is a safe, relatively cheap, and non-painful stimulation of the peripheral sensory and motor nerves. The stimulator is easy to operate and pwMS can apply the stimulation themselves at home. This makes TENS an interesting tool to augment sensory input. A high frequency and long pulse duration is used.
Experimental: active stimulation of the quadriceps	Device: Transcutaneous Electrical Nerve Stimulation; Transcutaneous electrical nerve stimulation (TENS) is a safe, relatively cheap, and non-painful stimulation of the peripheral sensory and motor nerves. The stimulator is easy to operate and pwMS can apply the stimulation themselves at home. This makes TENS an interesting tool to augment sensory input. A high frequency and long pulse duration is used.
Active Comparator: continuous movement of the foot (plantar & dorsiflexion)	Behavioral: Movement; Participants are instructed to perform plantar- and dorsi-flexion contraction in a relatively slow tempo. The movement of the ankle is measured by an MRI-compatible potentiometer and participants receive feedback of this movement on the screen inside the scanner.
Sham Comparator: a combination of sham stimulation of the tibialis anterior and movement of the foot	Device: Transcutaneous Electrical Nerve Stimulation; Transcutaneous electrical nerve stimulation (TENS) is a safe, relatively cheap, and non-painful stimulation of the peripheral sensory and motor nerves. The stimulator is easy to operate and pwMS can apply the stimulation themselves at home. This makes TENS an interesting tool to augment sensory input. A high frequency and long pulse duration is used.; Behavioral: Movement; Participants are instructed to perform plantar- and dorsi-flexion contraction in a relatively slow tempo. The movement of the ankle is measured by an MRI-compatible potentiometer and participants receive feedback of this movement on the screen inside the scanner.
Experimental: a combination of active stimulation of the tibialis anterior and movement of the foot	Device: Transcutaneous Electrical Nerve Stimulation; Transcutaneous electrical nerve stimulation (TENS) is a safe, relatively cheap, and non-painful stimulation of the peripheral sensory and motor nerves. The stimulator is easy to operate and pwMS can apply the stimulation themselves at home. This makes TENS an interesting tool to augment sensory input. A high frequency and long pulse duration is used.; Behavioral: Movement; Participants are instructed to perform plantar- and dorsi-flexion contraction in a relatively slow tempo. The movement of the ankle is measured by an MRI-compatible potentiometer and participants receive feedback of this movement on the screen inside the scanner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD activation due to TENS	Blood level detection activation (BOLD) changes and interaction networks before, during and after active TENS and differences in activation due to stimulation on quadriceps vs. tibialis anterior, stimulation on tibialis anterior vs plantar/dorsiflexion and stimulation on tibialis anterior vs stimulation combined with plantar/dorsiflexion. We focus on the thalamus (integration station of sensory input), sensory cortex (sensory awareness) and motor cortices (sensorimotor integration).	1 hour fMRI scan

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 22, 2024
• First Submitted That Met QC Criteria: May 22, 2024
• First Posted (Actual): May 29, 2024

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Multiple Sclerosis; Fatigue; Mobility Limitation; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Physiological Phenomena; Rehabilitation; Anesthesia and Analgesia; Electric Stimulation Therapy; Analgesia; Movement; Transcutaneous Electric Nerve Stimulation
• Other Study ID Numbers: MS-fMRI-TENS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No