rTMS for Fibromyalgia

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Disqualifiers: TMS contraindications, other chronic pain

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant physical limitations and impaired quality of life. There are several challenges that complicate the diagnosis and management of fibromyalgia. The etiology is not well defined, as there are several proposed factors that may trigger the genesis of pain in fibromyalgia including physical and/or emotional life stressors, and genetic predispositions involving neuromodulator pathways. Chronic pain in fibromyalgia arises in the absence of tissue pathology, and consequently a lack of consensus on reliable diagnostic criteria. Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective biomarkers for diagnosis. Therefore, the goals of this study are to: 1. Compare the neurophysiological responses in fibromyalgia compared to healthy controls. 2. Determine whether a two-week rTMS protocol will alter pain in individuals with fibromyalgia.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

Is rTMS safe for humans?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe for humans, with no serious adverse events reported in studies involving fibromyalgia patients. It has been used safely in various conditions, and while minor side effects can occur, they are typically mild and temporary. ^{1 2 3 4 5}

How does rTMS treatment differ from other treatments for fibromyalgia?

Repetitive Transcranial Magnetic Stimulation (rTMS) is a unique treatment for fibromyalgia because it is a non-invasive brain stimulation technique that targets specific brain areas to improve pain and mood, unlike traditional medications. It has shown promise in improving quality of life and health status in fibromyalgia patients, especially when other treatments are not effective. ^{3 4 6 7 8}

What data supports the effectiveness of the treatment rTMS for fibromyalgia?

Research shows that high-frequency rTMS can significantly improve the quality of life and health status in people with fibromyalgia. Studies comparing rTMS to a sham (fake) treatment found that it helps reduce pain and improve overall well-being. ^{3 4 9 10 11}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who have been diagnosed with fibromyalgia, a condition causing fatigue and chronic pain. It's not open to those with other chronic pain conditions or who can't safely undergo Transcranial Magnetic Stimulation (TMS) due to certain health risks.

Exclusion Criteria

I have no health conditions that prevent me from undergoing TMS.

I have chronic pain not caused by fibromyalgia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rTMS treatment for fibromyalgia, with active and sham groups receiving 10 Hz rTMS approximately 5 days per week for 2 weeks

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for changes in neurophysiological responses and pain levels after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Active Repetitive Transcranial Magnetic Stimulation (rTMS)
• Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study tests how Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique, affects the neurophysiology of fibromyalgia patients compared to inactive treatment. Participants will receive two weeks of either active rTMS or sham (inactive) therapy.

How Is the Trial Designed?

Group I: Active rTMS Active Control 1 Intervention

Repetitive Transcranial Magnetic Stimulation (rTMS) will be delivered at 10 Hz, 1500 pulses targeting the hand representation of the left primary motor cortex. rTMS delivery will require \~11 min to complete. In Experiment 1, this intervention will be performed for 1 session (\~11min). In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.

Group II: Sham rTMS Placebo Group 1 Intervention

Sham rTMS will be delivered at as a placebo control. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active rTMS. In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.

Active Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Anxiety Disorders

Approved in Canada as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

In a study of 38 fibromyalgia patients, those receiving high-frequency rTMS showed significant improvements in quality of life (QoL) after 10 weeks compared to those receiving sham stimulation, particularly in emotional and social aspects.

The improvement in QoL was linked to increased metabolism in the right medial temporal area of the brain, suggesting a neural basis for the emotional benefits of rTMS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS in fibromyalgia: a randomized trial evaluating QoL and its brain metabolic substrate. Boyer, L., Dousset, A., Roussel, P., et al.[2022]

A systematic review of 7 high-quality randomized controlled trials involving 217 patients found that 10-Hz repetitive transcranial magnetic stimulation (rTMS) significantly reduced pain and improved quality of life in individuals with fibromyalgia compared to sham stimulation.

While 10-Hz rTMS effectively alleviated pain (SMD=-0.72) and enhanced quality of life (SMD=-0.70), it did not show a significant impact on depression levels (SMD=-0.23), indicating its primary benefit lies in pain management rather than mood improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation at 10 Hz in Fibromyalgia: A Systematic Review and Meta-analysis. Zhu, PA., Xie, JY., Liu, H., et al.[2023]

In a study of 30 female patients with fibromyalgia, both high-frequency rTMS protocols (targeting the primary motor cortex and dorsolateral prefrontal cortex) led to significant improvements in pain, quality of life, and depression compared to a sham treatment.

The group receiving rTMS targeting the primary motor cortex showed the greatest reduction in pain, while the dorsolateral prefrontal cortex group had more significant improvements in physical role functioning, highlighting the potential of rTMS as an effective intervention for fibromyalgia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is high-frequency repetitive transcranial magnetic stimulation of the left primary motor cortex superior to the stimulation of the left dorsolateral prefrontal cortex in fibromyalgia syndrome? Altas, EU., Askin, A., Beşiroğlu, L., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been shown to significantly reduce pain in fibromyalgia patients, with 80% of rTMS studies and 100% of tDCS studies reporting positive outcomes.

Excitatory rTMS/tDCS targeting the primary motor cortex (M1) not only provided effective pain relief but also had fewer side effects compared to traditional fibromyalgia medications, making it a promising alternative for patients seeking relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Marlow, NM., Bonilha, HS., Short, EB.[2022]

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduces fibromyalgia symptoms, with a standardized mean difference of -0.700, indicating its efficacy in managing the disease's impact, especially in older patients.

The benefits of rTMS, including reductions in pain, depression, and anxiety, were observed to last for at least two weeks after treatment, and no serious adverse events were reported, highlighting its safety as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Su, YC., Guo, YH., Hsieh, PC., et al.[2021]

In a study involving 33 patients undergoing rTMS treatment, the sham condition used was effective as most participants could not distinguish between real and sham stimulation, indicating its suitability for clinical trials.

Both groups, those receiving real stimulation and those receiving sham, showed a high willingness to recommend rTMS to others, suggesting that the treatment is perceived positively regardless of the actual stimulation received.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial. Herwig, U., Cardenas-Morales, L., Connemann, BJ., et al.[2015]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Repetitive Transcranial Magnetic Stimulation on the Primary Motor Cortex of Individuals with Fibromyalgia: A Systematic Review and Meta-Analysis. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

rTMS in fibromyalgia: a randomized trial evaluating QoL and its brain metabolic substrate. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation at 10 Hz in Fibromyalgia: A Systematic Review and Meta-analysis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Is high-frequency repetitive transcranial magnetic stimulation of the left primary motor cortex superior to the stimulation of the left dorsolateral prefrontal cortex in fibromyalgia syndrome? [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Evidence for the improvement of fatigue in fibromyalgia: A 4-week left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation randomized-controlled trial. [2019]

10. Australia pubmed.ncbi.nlm.nih.gov

Analgesic effects of repetitive transcranial magnetic stimulation on modified 2010 criteria-diagnosed fibromyalgia: Pilot study. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

The effect of repetitive transcranial magnetic stimulation on fibromyalgia: a randomized sham-controlled trial with 1-mo follow-up. [2022]