Fatigue Alleviation Through Neuromodulating Therapy in Multiple Sclerosis

Summary

The goal of this clinical trial is to learn if repetitive Transcranial Magnetic Stimulation (rTMS) of the left premotor cortex can lessen fatigue in patients with Multiple Sclerosis, and if this is a feasible intervention. It will also give further information on fatigue in Multiple Sclerosis. The main questions it aims to answer is:

* Does premotor rTMS decrease fatigue symptoms in patients with Multiple Sclerosis?
* Is the change in fatigue reflected in an altered balance between brain excitation and inhibition in the targeted premotor cortex?

Researchers will compare real rTMS with sham rTMS (which does not stimulate with a magnetic field), to see if real rTMS works to alleviate fatigue.

Participants will:

* Receive real or sham rTMS for 30 minutes, 5 days in a row
* Visit the clinic before and 6 days after for baseline and follow-up
* Fill out on-line questionnaires 1 day and 4 weeks after the end of intervention
* Undergo a total of 3 brain scans (Magnetic Resonance Imaging at ultra-high field), at baseline, end of intervention, and follow-up
* Undergo lab neurophysiological measurements before and after the first intervention session
* Keep a fatigue diary and wear an activity tracker in the period before and after the intervention

Conditions

• Multiple Sclerosis, Relapsing-Remitting
• Fatigue

Interventions

DEVICE

Real Repetitive Transcranial Magnetic Stimulation

Five sessions of real paired-pulse rTMS at 0.72Hz (inter-pulse interval of 30ms and inter-pair interval of 1381ms), for a total of 1300 pulse-pairs (30 minutes), across 5 sequential days, Monday to Friday. The stimulation is applied with a MagPro XP Orange stimulator (MagVenture A/S, Farum, Denmark), through a B65-Cool-A/P-CO coil (Magventure A/S) with an active and placebo (sham) side. The active side is an actively cooled figure-of-eight coil with an outer diameter of 65mm. Intensity is 80% of resting motor threshold. It is kept the same across all 5 sessions. The target is the left PMd, at MNI coordinates (34, -2, 66), transformed into patient space. Optimal coil placement, with respects to induced e-field at the target coordinates, is simulated with SimNIBS, based on the participants own MR images. The coil positioning is guided and monitored continuously with a neuronavigation system (Localite, Bonn, Germany) and the aid of robotic arm (Axilum Robotics, Schiltigheim, France ).

DEVICE

Sham Repetitive Transcranial Magnetic Stimulation

Five sessions of real paired-pulse rTMS at 0.72Hz (inter-pulse interval of 30ms and inter-pair interval of 1381ms), for a total of 1300 pulse-pairs (30 minutes), across 5 sequential days, Monday to Friday. The stimulation is applied with a MagPro XP Orange stimulator (MagVenture A/S, Farum, Denmark), through a B65-Cool-A/P-CO coil (Magventure A/S) with an active and placebo (sham) side. The sham side does not deliver a magnetic pulse to the participant. The target is the left PMd, at MNI coordinates (34, -2, 66), transformed into patient space. Optimal coil placement, with respects to induced e-field at the target coordinates, is simulated with SimNIBS, based on the participants own MR images. The coil positioning is guided and monitored continuously with a neuronavigation system (Localite, Bonn, Germany) and the aid of robotic arm (Axilum Robotics, Schiltigheim, France ).

Sponsors & Collaborators

• Danish Multiple Sclerosis Center

  collaborator UNKNOWN

• Scleroseforeningen

  collaborator UNKNOWN

• Independent Research Fund Denmark

  collaborator INDUSTRY

• Danish Research Centre for Magnetic Resonance

  lead OTHER

Principal Investigators

• Hartwig R Siebner, MD, DMSc · Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre & University of Copenhagen

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-08-14

Primary Completion

2026-09-01

Completion

2026-11-01

Countries

• Denmark

Study Locations