Overview
Repetitive Transcranial Magnetic Stimulation (rTMS) of the motor cortex is a recognized analgesic technique for the treatment of fibromyalgia pain, which represents a largely unmet medical need. However, the effectiveness of motor cortex rTMS is inconsistent, being observed in only about 40% of patients and not always long-lasting. It has been previously shown that predictive factors for a lack of response to motor cortex rTMS include the presence of depressive symptoms, and that prefrontal cortex rTMS is not effective for pain, even though this treatment has proven efficacy in major depressive disorder.
The hypothesis is that targeting both the motor and prefrontal cortices with rTMS will yield a particularly beneficial effect in fibromyalgia patients presenting with comorbid depressive symptoms.
Given the absence of established biomarkers for predicting rTMS response, an additional aim will be to develop reliable indicators of rTMS efficacy, based on clinical phenotype and measurements of oscillatory patterns assessed by electroencephalogram (EEG) recordings.
Description
This is a monocentric, randomized, double-blind, parallel-group, sham-controlled trial. After providing informed consent, patients will first undergo brain magnetic resonance imaging (MRI) to determine the exact position of the coil for rTMS neuronavigation.
Clinical and psychological outcomes - assessed using validated self-report questionnaires - as well as neurophysiological parameters - including resting-state brain oscillatory activity (EEG) and cortical excitability measures (TMS and electromyography) - will be recorded at three time points: (i) at inclusion, approximately one week before treatment initiation; (ii) after completion of the 5-day intensive stimulation phase; and (iii) at the follow-up visit, two weeks after the end of treatment.
Correlations between the analgesic effects of active or sham rTMS and changes in clinical and electrophysiological parameters will be evaluated.
The treatment consists of 5 daily sessions of high-frequency rTMS of the motor and prefrontal cortex (one 30-minute session per day delivering 3000 pulses). This will be followed by: one session per week for the following 3 weeks; one session every 15 days during the following month.
This results in a total of 10 sessions over approximately 2 months.
Eligibility
Inclusion Criteria:
- Chronic pain lasting at least 6 months, with or without associated depressive symptoms;
- Fibromyalgia (2016 revised ACR criteria and a FIRST questionnaire score of at least 5 out of 6);
- Average pain intensity ≥ 4/10 on a 0-10 numeric rating scale;
- Pain present daily or almost daily (≥ 4 days per week);
- Patients aged over 18 and under 80 years;
- Patients who have provided written informed consent;
- Patients whose analgesic treatment has been stable for at least 1 month prior to inclusion and will not need to be modified during the study;
- Patients who can be followed for the duration of the study (10 weeks);
- Patients covered by a health insurance plan or otherwise eligible.
Exclusion Criteria:
- Ongoing litigation;
- Contraindication to rTMS:
- Implanted electronic devices and/or conductive objects near the coil: Patients with an active implanted device that is activated or controlled by physiological signals (e.g., pacemakers, implantable cardiac defibrillators \[ICD\], vagus nerve stimulators \[VNS\], wearable cardioverter defibrillators \[WCD\], ocular implants, deep brain stimulation systems, drug infusion pumps or ports, intracardiac leads), even if the device has been removed.
- Non-removable metallic objects near the coil:\*\* Patients with a conductive, ferromagnetic, or magnetically sensitive metal implant in the head or within 30 cm of the coil (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, or bullet fragments);
- Current abuse of drugs or psychoactive substances, including alcohol (according to DSM-5 criteria);
- Pregnancy or breastfeeding;
- Epilepsy or a history of epilepsy;
- Unstable or progressive medical conditions (e.g., cancer);
- Psychosis according to DSM-5 criteria;
- Presence of another pain condition more severe than the one qualifying for inclusion;
- Failure to correctly complete pain self-assessment diaries between inclusion and randomization (fewer than 4 pain scores recorded over 7 days);
- Inability to understand the informed consent form, or subjects under legal guardianship or curatorship;
- Participation in another research protocol within 30 days prior to inclusion.
