Intermittent Theta-Burst Stimulation for Lower-Limb Spasticity and Pain in Multiple Sclerosis

ConditionsMultiple Sclerosis Muscle Spasticity Neuropathic Pain

Trial statusNot yet recruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18+

SponsorComenius University

About this trial

Spasticity and neuropathic pain are frequent and disabling symptoms of multiple sclerosis. Intermittent theta-burst stimulation (iTBS) is a non-invasive neuromodulation technique that may modulate cortical and corticospinal excitability and thereby improve motor symptoms and pain. This randomized, parallel-group, sham-controlled, assessor-blinded study will evaluate the clinical efficacy of active iTBS compared with sham stimulation in adults with multiple sclerosis and clinically significant lower-limb spasticity and pain. Participants will receive five stimulation sessions over one week. Spasticity, pain, patient-reported outcomes, and the electrophysiological H/M ratio will be assessed at baseline and at Weeks 2 and 4 after the intervention.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosis of multiple sclerosis according to the 2024 McDonald criteria.

Expanded Disability Status Scale (EDSS) score from 2.5 to 6.0.

Clinically significant spasticity in at least one muscle group of the more affected lower limb, defined as a Modified Tardieu Scale quality of muscle reaction score of at least 2 at velocity V3.

Lower-limb pain intensity of at least 4/10 on a 0-10 Visual Analogue Scale at screening.

Disqualifiers

Epilepsy or another condition associated with an increased risk of seizure.

Metallic implants, implanted electronic devices, or other conditions contraindicating transcranial magnetic stimulation.

Clinical relapse of multiple sclerosis within 30 days before enrolment.

Pregnancy or breastfeeding.

Trial design

Design model

Parallel

Treatments tested in this trial

Active Intermittent Theta-Burst Stimulation (iTBS)
Device
Active iTBS will be delivered using a Neuro-MS/D Advanced Therapeutic magnetic stimulator (Neurosoft) with a figure-of-eight coil. The stimulation target will be the representation of the muscle group corresponding to the dominant spastic pattern of the more affected lower limb in the contralateral primary motor cortex. The target will be identified using motor-evoked potentials and neuronavigation based on the participant's individual MRI. Active motor threshold will be determined from the tibialis anterior muscle. Stimulation intensity will be set at 80% of the active motor threshold. Each burst will consist of 3 pulses at 50 Hz, repeated at 5 Hz. Each 600-pulse block will use a 2-second on/8-second off pattern and last approximately 3 minutes 9 seconds. Two 600-pulse blocks will be delivered per day, separated by a 15-minute interval, for a total of 1,200 pulses per day. Treatment will be administered on five consecutive weekdays, giving 10 stimulation blocks in total.
Sham Intermittent Theta-Burst Stimulation
Device
In both groups, the TMS coil will be positioned over the primary motor cortex representation of the more affected lower limb and sham electrodes will be attached to the forehead. During sham stimulation, surface electrodes placed on the forehead will deliver low-intensity electrical stimulation at 2 mA to reproduce the somatosensory experience of TMS. The TMS device will simultaneously produce the characteristic clicking sound of coil discharge. The software will conceal the assigned mode from the participant and stimulation operator. The visit schedule, positioning, and total procedural duration will match the active condition.

Treatment groups

40 Participants

are divided into 2 treatment groups

Group A: active iTBSExperimental treatment 1 intervention

Group B: sham iTBSSham comparator 1 intervention

Trial outcomes

Primary outcomes

The Modified Tardieu Scale Quality of Muscle Reaction Score

The entire more affected lower limb will be examined using the Modified Tardieu Scale. At baseline, the muscle group corresponding to the dominant spastic pattern will be predefined as the individual target muscle group and the same muscle group will be reassessed at all subsequent visits. The quality of muscle reaction at fast stretch velocity V3 is scored from 0 to 5, where 0 indicates no resistance and higher scores indicate a more pronounced catch or clonus; a lower score indicates less spasticity.

Time frame