Analgesic Efficacy of Multisite rTMS in Fibromyalgia Patients
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-80
SponsorHospital Ambroise Paré Paris
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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);
Disqualifiers
Ongoing litigation;
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);
Trial design
Design model
Parallel
Treatments tested in this trial
rTMS
DeviceThe active protocol will include 5 daily stimulation sessions during the first week (D1-D5), followed by one session per week for 3 weeks (W2, W3, W4), then 2 sessions spaced 2 weeks apart (W6, W8), for a total of 10 stimulation sessions. Evaluation will continue until 2 weeks after the final stimulation, that is, at week 10 after the start of treatment.
Sham
DeviceThe sham protocol will follow an identical session schedule. Participants will be randomized to either the active or sham group in a parallel-group design, meaning each participant will receive only one of the two treatments throughout the entire duration of the study.
Treatment groups
36 Participants
are divided into 2 treatment groupsGroup A: Active rTMS of motor and prefrontal cortexExperimental treatment 1 intervention
Group B: Sham rTMS of motor and prefrontal cortexSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in average pain intensity over 10 weeks (Brief Pain Inventory)
The primary outcome measure will be the mean change from baseline over the course of 10 weeks (group x time interaction) in average pain intensity from the Brief Pain Inventory (scored on a 0-10 NRS with 0 = no pain and 10 = maximal pain intensity). Baseline average pain intensity will be assessed at inclusion, and just before the first rTMS session (Day 1) and will correspond to the average of these two values. Pain intensity will be further assessed immediately before each rTMS session at Days 2, 3, 4, 5 then at weeks 2, 3, 4, 6, 8, and finally 2 weeks after the last rTMS session at week 10.
Time frame
From enrollment to Week 10.Secondary outcomes
1
Weekly pain, fatigue and sleep disturbances
Weekly average of daily patient-reported scores for pain intensity, fatigue, and sleep disturbance, recorded in a self-assessment diary completed throughout the study. Pain intensity and fatigue are each assessed on a numerical rating scale from 0 (no pain/no fatigue) to 10 (worst imaginable pain/worst imaginable fatigue), where higher scores indicate worse outcome. Sleep disturbance is assessed on a numerical rating scale from 0 (no interference) to 10 (completely disrupted sleep), where higher scores indicate worse outcome.
Time frame
At each visit from baseline to Week 10.2
Immediate effect of rTMS on pain intensity
Pain intensity at the present moment assessed immediately after each rTMS session using a Numerical Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain).
Time frame
At each visit from baseline to Week 10.3
Onset of the therapeutic effect
The time to onset of the therapeutic effect from the first stimulation, assessed by measuring 24-hour pain scores recorded in the patient's self-assessment diary.
Time frame
At each visit from baseline to Week 10.4
Brief Pain Inventory (BPI)
The validated French version of the BPI (Cleeland and Ryan, 1994) will be used to assess maximum and minimum pain over the past 24 hours and at the present moment, as well as the impact of pain (general activity, mood, ability to walk, usual work, relationships with others, sleep, quality of life), on numerical scales from 0 to 10.
Time frame
From enrollment to Week 10.Other outcomes
1
Predictive value of baseline clinical variables on treatment response to active rTMS and sham
Assess the correlation between baseline clinical variables - including pain characteristics, demographic factors, and psychosocial factors - and treatment response to active rTMS and sham stimulation.
Time frame
From enrollment to Week 10.2
Predictive value of baseline intracortical excitability and inhibition parameters assessed with TMS on treatment response to active rTMS and sham
Identify the correlation between motor cortical excitability and inhibition - assessed via motor evoked potentials (recorded from the first dorsal interosseous muscle of the hand) elicited by paired-pulse TMS - and treatment response to active rTMS and sham stimulation.
Time frame
From enrollment to Week 10.3
Predictive value of baseline cortical oscillatory EEG biomarkers on treatment response to active rTMS and sham
Identify the correlation between baseline cortical oscillatory patterns extracted from resting-state EEG recordings and treatment response to active rTMS and sham stimulation. EEG recordings will consist of a 5-minute eyes-open and a 5-minute eyes-closed session using a 32-channel cap.
Time frame
From enrollment to Week 10.Sponsors and contacts
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Source ClinicalTrials.gov