## Protocol Section
### Identification Module
**NCT ID:** NCT06432686

**Brief Title:** Neurophysiological Effects of Transcutaneous Electrical Nerve Stimulation in Persons With MS

**Official Title:** Neurophysiological Effects of Transcutaneous Electrical Nerve Stimulation in Persons With MS - a Pilot Study

#### Organization Study ID Info
**ID:** MS-fMRI-TENS
#### Organization
**Class:** OTHER
**Full Name:** University Medical Center Groningen
### Status Module
#### Completion Date
**Date:** 2025-07-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-07-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-22
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Medical Center Groningen

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Walking Difficulties, Fatigue, Transcutaneous Electrical Nerve Stimulation

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** * sham stimulation of the tibialis anterior,
* active stimulation of the tibialis anterior,
* active stimulation of the quadriceps,
* continuous movement of the foot (plantar \& dorsiflexion),
* a combination of sham stimulation of the tibialis anterior and movement of the foot,
* a combination of stimulation of the tibialis anterior and movement of the foot.

The order of these conditions is randomized.

##### Masking Info

**Masking:** SINGLE

**Masking Description:** All participants receive both active and sham TENS. Subjects will be told they will get two types of stimulation but they are not being told that one is 'sham' and the other 'active', to minimalize a placebo effect. Researchers are not blinded, but also interacting minimally with the participant while they are lying in the scanner.

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Device: Transcutaneous Electrical Nerve Stimulation

**Label:** sham stimulation of the tibialis anterior

**Type:** SHAM_COMPARATOR

#### Arm Group 2

**Intervention Names:**

- Device: Transcutaneous Electrical Nerve Stimulation

**Label:** active stimulation of the tibialis anterior

**Type:** EXPERIMENTAL

#### Arm Group 3

**Intervention Names:**

- Device: Transcutaneous Electrical Nerve Stimulation

**Label:** active stimulation of the quadriceps

**Type:** EXPERIMENTAL

#### Arm Group 4

**Intervention Names:**

- Behavioral: Movement

**Label:** continuous movement of the foot (plantar & dorsiflexion)

**Type:** ACTIVE_COMPARATOR

#### Arm Group 5

**Intervention Names:**

- Device: Transcutaneous Electrical Nerve Stimulation

- Behavioral: Movement

**Label:** a combination of sham stimulation of the tibialis anterior and movement of the foot

**Type:** SHAM_COMPARATOR

#### Arm Group 6

**Intervention Names:**

- Device: Transcutaneous Electrical Nerve Stimulation

- Behavioral: Movement

**Label:** a combination of active stimulation of the tibialis anterior and movement of the foot

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- a combination of active stimulation of the tibialis anterior and movement of the foot

- a combination of sham stimulation of the tibialis anterior and movement of the foot

- active stimulation of the quadriceps

- active stimulation of the tibialis anterior

- sham stimulation of the tibialis anterior

**Description:** 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.

**Name:** Transcutaneous Electrical Nerve Stimulation

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- a combination of active stimulation of the tibialis anterior and movement of the foot

- a combination of sham stimulation of the tibialis anterior and movement of the foot

- continuous movement of the foot (plantar & dorsiflexion)

**Description:** 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.

**Name:** Movement

**Type:** BEHAVIORAL

### Outcomes Module

#### Primary Outcomes

**Description:** 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).

**Measure:** BOLD activation due to TENS

**Time Frame:** 1 hour fMRI scan

### Eligibility Module

**Eligibility Criteria:** 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

**Healthy Volunteers:** True

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** n.dreijer@umcg.nl

**Name:** Nikki Dreijer

**Phone:** 0625647172

**Role:** CONTACT

**Contact 2:**

**Email:** c.a.t.zijdewind@umcg.nl

**Name:** Inge Zijdewind

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M8364

- Name: Fatigue

- Relevance: HIGH

- As Found: Fatigue

### Condition Browse Module - Meshes

- ID: D000005221

- Term: Fatigue

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Gast

- Name: Gastrointestinal Agents

### Intervention Browse Module - Browse Leaves

- ID: M251057

- Name: TEMPO

- Relevance: LOW

- As Found: Unknown

- ID: M186190

- Name: Aluminum hydroxide, magnesium hydroxide, simethicone drug combination

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
