aiTBS and rTMS in Neuropathic Pain and Prediction of Response

Summary

This study evaluates the analgesic benefit of two non-invasive brain stimulation techniques: high frequency repetitive transcranial magnetic stimulation (rTMS) and accelerated intermittent theta burst stimulation (aiTBS) - compared to sham stimulation, in patients with chronic neuropathic pain lasting at least 6 months.

Transcranial magnetic stimulation, which is delivered by a coil positioned on the scalp over the motor cortex, generates a low-intensity, submotor-threshold electromagnetic field that noninvasively activates targeted brain regions involved in pain perception. The procedure is painless and non-invasive. Sham stimulation uses the inactive face of the same coil and produces an identical sound, ensuring that neither patients nor investigators know which stimulation is being delivered.

Conventional rTMS has demonstrated moderate analgesic efficacy in neuropathic pain, but its effect is delayed and requires at least 5 treatment sessions. iTBS delivers the same total stimulation dose in a much shorter time (approximately 8 minutes per session versus 30 minutes for conventional rTMS) and enables accelerated protocols with multiple sessions per day, which have shown promising results in depression.

This study compares aiTBS, rTMS and sham by a randomized controlled trial (RCT) with a crossover design: participants are randomized in a 2:1 ratio to receive either active stimulation (both techniques in sequence) or sham stimulation (both techniques in sequence). Each treatment phase consists of either 5 consecutive daily rTMS sessions or 5 aiTBS sessions delivered on a single day (with a 45-min pause between sessions). The cross-over will take place after a 4 to 6-week washout period between the two active or sham treatments. The total study duration per participant is from 10 to 12 weeks, with 11-12 in-person visits.

Assessments include self-reported pain diaries numeric pain rating scale (NPRS), validated pain, psychosocial, and quality-of-life questionnaires, resting-state Electroencephalography (EEG) recordings, and transcranial magnetic stimulation (TMS) based measures of intracortical excitability and inhibition. The exploratory aim is to identify neurophysiological and clinical predictors of treatment response, to better personalize the treatment in chronic pain population.

Conditions

• Chronic Neuropathic Pain

Interventions

DEVICE

Active rTMS, active aiTBS, sham rTMS or sham aiTBS

The active rTMS treatment consists of 5 sessions (1 per day for 5 consecutive days), each lasting 20 minutes. Each session consists of 15 trains of 10-s pulses at 10 Hz with an inter-train interval of 50 s, delivering 1500 pulses per session for a total of 7500 pulses. The active aiTBS treatment consists of 5 sessions delivered in a single day. Each session lasts 8 minutes, with an inter-session interval of 45 minutes and a 110-minute intervel between the third and fourth sessions. Each burst consists of 3 pulses at 50 Hz; bursts are repeated within a train of 10 bursts at 5 Hz. Each cycle consists of 2 s of train stimulation followed by 8 s of pause. One session is composed of 50 cycles, delivering 1500 pulses per session for a total of 7500 pulses. The sham stimulation will follow the same posology and modality of administration but opposite bobine face

Sponsors & Collaborators

• Hospital Ambroise Paré Paris

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-09-30

Primary Completion

2028-09-30

Completion

2028-09-30

Countries

• France

Study Locations