Repetitive Transcranial Magnetic Stimulation for Endometriosis Pain

Overseen By Linda McLean, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Ottawa

Disqualifiers: Epilepsy, Pregnancy, Infections, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1-2 weeks

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover better methods to reduce pain for individuals with endometriosis, a condition that causes persistent pain even after treatment. Researchers are testing repetitive transcranial magnetic stimulation (rTMS), which uses magnetic fields to stimulate the brain, to determine its effectiveness in easing this pain. The trial will compare different treatment plans to identify which works best and how long the benefits last. It seeks participants with ongoing endometriosis pain that hasn't improved with other medical or surgical treatments. As an unphased trial, participants can contribute to innovative research that may lead to new pain relief options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that repetitive transcranial magnetic stimulation is safe for treating endometriosis-associated pain?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally well-tolerated. In previous studies, rTMS effectively reduced pain, especially for long-term conditions like endometriosis. One study found that patients experienced at least a 10% improvement in pain levels after treatment. Another review highlighted that rTMS safely manages pain by controlling brain activity related to pain perception. While minor side effects, such as mild headaches or discomfort at the treatment site, can occur, they usually resolve quickly and are not serious. Overall, current evidence supports the safety of rTMS for managing pain in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it offers a non-invasive approach to managing endometriosis pain by using magnetic fields to stimulate specific areas of the brain. Unlike traditional treatments like pain relievers, hormonal therapies, or surgery, rTMS targets the brain's pain processing centers directly, potentially reducing pain without the side effects associated with medication. Researchers are particularly excited about rTMS because it can be tailored to individual patients, offering a personalized treatment option that could provide relief faster than conventional therapies. Moreover, the flexibility of delivering sessions over five or ten days provides options for optimizing treatment effectiveness.

What evidence suggests that repetitive transcranial magnetic stimulation could be an effective treatment for endometriosis pain?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) might help reduce pain in people with endometriosis. In one study, 75% of participants reported an improvement in their pain. Another study found that nine out of ten participants experienced less chronic pelvic pain. These results suggest that rTMS could be a promising method for managing pain from endometriosis. In this trial, participants will receive either real or sham rTMS in different treatment arms. The treatment uses magnetic pulses to stimulate brain areas involved in pain perception, potentially altering how pain is experienced. ^{1 3 6 7 8}

Who Is on the Research Team?

Linda McLean, PhD

Principal Investigator

University of Ottawa

Are You a Good Fit for This Trial?

This trial is for Canadian women, girls, and gender-diverse individuals newly diagnosed with endometriosis who experience chronic pain after other interventions. Participants should have persistent post-operative endometriosis-associated pain.

Inclusion Criteria

I have endometriosis pain above 3 despite treatment.

Exclusion Criteria

Pregnancy

My family has a history of epilepsy.

My pain is more severe and not just in my pelvic area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) intervention, either real or sham, over 5 or 10 sessions

1-2 weeks

5-10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including daily pain recording for 30 days

30 days

Remote monitoring

Long-term Follow-up

Participants provide feedback on pain and satisfaction 6 months after the intervention

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The study tests if repetitive transcranial magnetic stimulation (rTMS) can reduce chronic pain in endometriosis patients. It compares real rTMS against a sham (placebo) treatment over two different durations: short-term (5 sessions) and long-term (10 sessions).

How Is the Trial Designed?

Group I: Real RepetitiveTranscranial Magnetic Stimulation (rTMS) 5 sessions Experimental Treatment 1 Intervention

The real rTMS intervention will be delivered to the primary motor cortex (M1) on the left side, over the hand representation, using high frequency (HF) rTMS applied by way of a Magstim Rapid² system. The coil position and orientation will be standardized between treatment visits through using a Brainsight neuronavigation system (Rogue Research, Canada). Each of 5 rTMS sessions will consist of a total of 1500 pulses: 15 sets of pulses delivered at 10Hz for 10s at 80% resting motor threshold (RMT), separated by 50s intervals. The real rTMS intervention will be delivered daily over 5 consecutive days.

Group II: Real RepetitiveTranscranial Magnetic Stimulation (rTMS) 10 sessions Experimental Treatment 1 Intervention

The real 10-session rTMS intervention will be the same as that delivered for the real 5-session rTMS intervention, but delivered as 5 daily sessions, a two day break, and 5 more daily sessions.

Group III: Sham RepetitiveTranscranial Magnetic Stimulation (rTMS) 5 sessions Placebo Group 1 Intervention

The sham rTMS intervention will be delivered to the primary motor cortex (M1) on the left side, over the hand representation, using high frequency (HF) rTMS applied by way of a Magstim Rapid² system interfaced with a placebo coil, whose position and orientation will standardized between treatment visits using a Brainsight neuronavigation system (Rogue Research, Canada) The sham stimulation target will be individually defined at baseline as the site eliciting the highest averaged motor evoked potential (MEP) peak-to-peak amplitude in the first dorsal interosseous (FDI) muscle. Each of 5 sham rTMS sessions will consist of a total of 1500 sham pulses: 15 sets of sham pulses (0% output) delivered at 10Hz for 10s, separated by 50s intervals. The sham intervention will be delivered daily over 5 consecutive days.

Group IV: Sham RepetitiveTranscranial Magnetic Stimulation (rTMS) 10 sessions Placebo Group 1 Intervention

The sham 10 session rTMS intervention will be delivered identically to the sham 5 session intervention, but delivered as 5 daily sessions, a two day break, and 5 more daily sessions.

Repetitive Transcranial Magnetic Stimulation 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
• Obsessive-compulsive disorder
• Anxiety disorders

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

University of Ottawa

Lead Sponsor

Trials

231

Recruited

267,000+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex was found to be well tolerated in a pilot study of 12 women with chronic pelvic pain due to endometriosis, with no serious adverse effects reported.

Nine out of twelve participants experienced significant reductions in pain intensity and interference, suggesting that rTMS may be an effective treatment option for chronic pelvic pain when other treatments have not worked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation Therapy (rTMS) for Endometriosis Patients with Refractory Pelvic Chronic Pain: A Pilot Study. Pinot-Monange, A., Moisset, X., Chauvet, P., et al.[2020]

Women with chronic pelvic pain (CPP) associated with endometriosis showed decreased gray matter volume in key brain regions related to pain processing, indicating potential changes in brain morphology due to chronic pain.

Even women with CPP but without endometriosis exhibited similar decreases in gray matter volume, suggesting that alterations in the central pain system contribute to chronic pain development, independent of endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. As-Sanie, S., Harris, RE., Napadow, V., et al.[2022]

Depot medroxyprogesterone acetate (DMPA-SC 104) is as effective as leuprolide in reducing endometriosis-associated pain over an 18-month period, with significant improvements in multiple pain categories.

DMPA-SC 104 causes significantly less decline in bone mineral density compared to leuprolide, and BMD levels return to pre-treatment levels 12 months after stopping DMPA-SC 104, indicating a safer profile for bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Crosignani, PG., Luciano, A., Ray, A., et al.[2022]

Medical therapy is the first line of management for endometriosis, with options like NSAIDs, combined oral contraceptives, and progestins being effective in relieving pain and preventing disease recurrence, while also being well tolerated and cost-effective.

Gonadotropin-releasing hormone agonists are effective for patients who do not respond to first-line treatments, but they have a less favorable safety profile and require additional therapy; promising new treatments, such as gonadotropin-releasing hormone antagonists, are currently in late-stage clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of medical treatment of endometriosis. Martone, S., Troìa, L., Marcolongo, P., et al.[2021]

Women with endometriosis showed significantly lower pain tolerance compared to healthy controls, indicating altered pain processing in this condition.

Understanding the mechanisms of pain in endometriosis may lead to new treatment options, suggesting that approaches like pain education and cognitive therapy could complement traditional surgical and pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental pain tolerance is decreased and independent of clinical pain intensity in patients with endometriosis. van Aken, M., Oosterman, J., van Rijn, T., et al.[2019]

Transcranial direct current stimulation (tDCS) was used as a noninvasive treatment for a 32-year-old woman with chronic pain from endometriosis, resulting in a 60% reduction in pain symptoms after 10 sessions.

At a 4-month follow-up, the patient reported a sustained 30% decrease in pain, indicating that tDCS may provide long-term relief for chronic pain associated with endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-lasting analgesic effect of transcranial direct current stimulation in treatment of chronic endometriosis pain. Rostami, R., Badran, BW., Kazemi, R., et al.[2017]

In a pilot study involving seven adult women with refractory chronic pelvic pain syndrome (CPPS), the combination of repetitive transcranial magnetic stimulation (rTMS) and focal muscle vibration (FMV) was found to be safe, with no serious adverse effects reported.

The treatment led to a significant reduction in pain, with an average decrease of 15 points on the visual analog scale (VAS) at day 7, and some participants maintained pain relief even one month after treatment, indicating potential efficacy for managing CPPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When Two Is Better Than One: A Pilot Study on Transcranial Magnetic Stimulation Plus Muscle Vibration in Treating Chronic Pelvic Pain in Women. Calabrò, RS., Billeri, L., Porcari, B., et al.[2022]

A randomized controlled trial will assess the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on chronic pelvic pain syndrome (CPPS) in 63 female participants, comparing high-intensity and low-intensity rTMS against a sham treatment.

The study aims to evaluate pain relief and psychological outcomes using various scales, with the high-intensity group receiving 15,000 pulses at 110% resting motor threshold, potentially demonstrating the efficacy of rTMS as a treatment option for CPPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of high-frequency repetitive transcranial magnetic stimulation under different intensities upon rehabilitation of chronic pelvic pain syndrome: protocol for a randomized controlled trial. Wang, M., Xia, R., Shi, J., et al.[2023]

This study aims to systematically review and analyze randomized controlled trials (RCTs) to determine the effectiveness and safety of neuromuscular electrical stimulation (NMES) for treating endometriosis-related pain, which is a common and debilitating condition.

The findings from this systematic review will help inform clinicians and guide future research on NMES as a potential treatment option for managing pain associated with endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of neuromuscular electrical stimulation for endometriosis-related pain: A protocol of systematic review and meta-analysis. Zhang, ZY., Wang, J., Fan, YL., et al.[2022]

Citations

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Repetitive Transcranial Magnetic Stimulation Therapy (rTMS ... This study is the first to study rTMS in the management of endometriosis using a protocol proven effective for neuropathic pain and fibromyalgia ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03204682

Study Details | NCT03204682 | Repetitive Transcranial ... The aim of the study is to evaluate the feasibility of transcranial magnetic stimulation (rTMS) for analgesia on chronic refractory endometriosis pain.

3. ctv.veeva.com ctv.veeva.com/study/is-repetitive-transcranial-magnetic-stimulation-effective-in-reducing-endometriosis-associated-pain

Is Repetitive Transcranial Magnetic Stimulation Effective in ... which suggested that 75% of participants (9 of 12) will be improved on the PGIC, and that there will be a reduction in reported pain sensitivity ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31013910/

Repetitive Transcranial Magnetic Stimulation Therapy ... The objective of this study was to assess the feasibility and effect of rTMS to reduce pain and improve quality of life (QoL) in patients with chronic pelvic ...

5. withpower.com withpower.com/trial/repetitive-transcranial-magnetic-stimulation-for-endometriosis-pain-0ce53

Repetitive Transcranial Magnetic Stimulation for ... Research suggests that Repetitive Transcranial Magnetic Stimulation (rTMS) may help reduce chronic pelvic pain in women with endometriosis, as nine out of ...

6. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00114/full

Effect of Repetitive Transcranial Magnetic Stimulation on ... Results from these studies showed that 10-Hz rTMS sessions effectively reduced pain according to the VAS. A study conducted by Hirayama et al. ( ...

7. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07082-w

Effect of high-frequency repetitive transcranial magnetic ... rTMS has been shown to regulate the central lesions caused by chronic diseases by inhibiting and reversing neuronal sensitization [20, 30, 31].

8. jcmimagescasereports.org jcmimagescasereports.org/article/JCM-V3-1393.pdf

Review article Repetitive TMS. (rTMS) may be considered a safe method to regulate cortical excitability and pain thresholds, and the analgesic effect of. rTMS ...