Analgesic Efficacy of Multisite rTMS in Fibromyalgia Patients

NCT07642882 | Recruiting

• 1 other identifier: 2025-A01369-40
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Fibromyalgia; Depression - Major Depressive Disorder; Chronic Pain

Keywords

Fibromyalgia; Chronic Pain; rTMS; Depression; Neuromodulation; EEG

Outcome Measures

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.

  From enrollment to Week 10.

Secondary Outcomes (16)

• Weekly pain, fatigue and sleep disturbances

  At each visit from baseline to Week 10.

• Immediate effect of rTMS on pain intensity

  At each visit from baseline to Week 10.

• Onset of the therapeutic effect

  At each visit from baseline to Week 10.

• Brief Pain Inventory (BPI)

  From enrollment to Week 10.

• Fibromyalgia Impact Questionnaire (FIQ)

  At baseline, after 5 days of treatment, at weeks 4, 6, 8 and 10.

Other Outcomes (3)

• Predictive value of baseline clinical variables on treatment response to active rTMS and sham

  From enrollment to Week 10.

• Predictive value of baseline intracortical excitability and inhibition parameters assessed with TMS on treatment response to active rTMS and sham

  From enrollment to Week 10.

• Predictive value of baseline cortical oscillatory EEG biomarkers on treatment response to active rTMS and sham

  From enrollment to Week 10.

Study Arms (2)

Active rTMS of motor and prefrontal cortex

EXPERIMENTAL

Each rTMS session for each cortical target will include 30 trains of pulses delivered at 10 Hz for 10 seconds (100 pulses per train), with a 20-second interval between each train, resulting in a total of 3,000 pulses per session. The total duration will be 15 to 20 minutes per target, and 30 to 40 minutes for both cortical targets combined. The stimulation intensity for the left motor cortex will be set at 80% of the resting motor threshold, defined as the minimal stimulation intensity that induces an electromyographic response of ≥50 µV in the first dorsal interosseous muscle of the hand, contralateral to the stimulated hemisphere, in at least 5 out of 10 trials. For stimulation of the left prefrontal cortex, we will use a stimulation intensity of 120% of the motor threshold, as is customary in psychiatry and as in our previous studies on analgesia (Attal et al., 2021).

Device: rTMS

Sham rTMS of motor and prefrontal cortex

SHAM COMPARATOR

To perform the rTMS, a figure-of-eight Cool-B65 A/P coil (MagVenture) will be used. This coil features a symmetrical design with two indistinguishable faces-one for active stimulation and the other for sham stimulation. The side used for each rTMS session will be determined by a personalized USB key for each patient, which will be connected to the rTMS device. The sound emitted during stimulation will be identical regardless of the side of the coil used. Finally, to further strengthen the treatment blinding for both the patient and the operator, the scalp-tapping sensation induced by active rTMS will be mimicked by low-intensity electrical stimulation applied to the head via surface electrodes. This electrical stimulation will be synchronized with the magnetic pulses during both active and sham stimulation sessions.

Device: Sham

Interventions

rTMS DEVICE

The 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.

Active rTMS of motor and prefrontal cortex

Sham DEVICE

The 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.

Sham rTMS of motor and prefrontal cortex

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 who can be followed for the duration of the study (10 weeks);
• Patients covered by a health insurance plan or otherwise eligible.

You may not qualify if:

• 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;
• Inability to understand the informed consent form, or subjects under legal guardianship or curatorship;

Sponsors & Collaborators

• Hospital Ambroise Paré Paris: lead

Study Sites (1)

Hopital Ambroise-Paré INSERM U987, 9 Av. Charles de Gaulle

Boulogne-Billancourt, Île-de-France Region, 92100, France

RECRUITING

Related Publications (6)

• Attal N, Poindessous-Jazat F, De Chauvigny E, Quesada C, Mhalla A, Ayache SS, Fermanian C, Nizard J, Peyron R, Lefaucheur JP, Bouhassira D. Repetitive transcranial magnetic stimulation for neuropathic pain: a randomized multicentre sham-controlled trial. Brain. 2021 Dec 16;144(11):3328-3339. doi: 10.1093/brain/awab208.

  PMID: 34196698 BACKGROUND

• Lapa JDDS, da Silva VA, Ciampi de Andrade D. Repetitive transcranial magnetic stimulation for fibromyalgia: are we there yet? Pain Rep. 2025 Jan 13;10(1):e1221. doi: 10.1097/PR9.0000000000001221. eCollection 2025 Feb.

  PMID: 39816903 BACKGROUND

• Ciampi de Andrade D, Valiengo L. Differential Effects of Repetitive Transcranial Magnetic Stimulation on Mood and Pain Symptoms in People With Chronic Pain and Major Depressive Disorders-A Review. Eur J Pain. 2025 Aug;29(7):e70077. doi: 10.1002/ejp.70077.

  PMID: 40693547 BACKGROUND

• Silva VA, Baptista AF, Fonseca AS, Carneiro AM, Brunoni AR, Carrilho PEM, Lins CC, Kubota GT, Fernandes AMBL, Lapa JDS, Dos Santos LM, Sasso I, Monte-Silva K, Poindessous-Jazat F, Mori N, Miki K, Baltar A, Tanaka C, Teixeira MJ, Hosomi K, Bouhassira D, Attal N, Ciampi de Andrade D. Motor cortex repetitive transcranial magnetic stimulation in fibromyalgia: a multicentre randomised controlled trial. Br J Anaesth. 2025 Jun;134(6):1756-1764. doi: 10.1016/j.bja.2024.12.045. Epub 2025 Mar 13.

  PMID: 40087077 BACKGROUND

• Passard A, Attal N, Benadhira R, Brasseur L, Saba G, Sichere P, Perrot S, Januel D, Bouhassira D. Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia. Brain. 2007 Oct;130(Pt 10):2661-70. doi: 10.1093/brain/awm189. Epub 2007 Sep 14.

  PMID: 17872930 BACKGROUND

• Mhalla A, Baudic S, de Andrade DC, Gautron M, Perrot S, Teixeira MJ, Attal N, Bouhassira D. Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia. Pain. 2011 Jul;152(7):1478-1485. doi: 10.1016/j.pain.2011.01.034. Epub 2011 Mar 11.

  PMID: 21397400 BACKGROUND

MeSH Terms

Conditions

Fibromyalgia; Chronic Pain; Depression

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Central Study Contacts

Nadine ATTAL

CONTACT

+33 1 49 09 59 31; nadine.attal@aphp.fr

Elisa UMMARINO

CONTACT

+33 1 49 09 45 56; elisa.ummarino@inserm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinator

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 11, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: June 11, 2026

Record last verified: 2026-06

Locations

FR (1)