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

Trial Summary

What is the purpose of this trial?

The goal of this research is to improve pain outcomes for the over 500K Canadian women, girls and gender-diverse individuals who are newly diagnosed with endometriosis each year. Chronic pain that persists after interventions for endometriosis is a huge problem. There is some evidence that endometriosis-associated pain (EAP) is, at least to some extent, associated with changes in pain physiology, particularly central sensitization of pain. There is currently no effective evidence-informed intervention that addresses EAP. Yet a recent feasibility trial on a repetitive transcranial magnetic stimulation (rTMS) intervention demonstrated promising results compared to a sham intervention for reducing pain in a sample with EAP. The objectives of this trial are: 1. to evaluate the effectiveness of an rTMS intervention for pain reduction among those with recalcitrant post-operative EAP, 2. to inform on the utility of a long (10 session) vs short (5 session) protocol for pain reduction among those with recalcitrant post-operative EAP 3. to determine if any improvements in pain observed 30 days after an rTMS intervention are retained 6 months later 4. to identify physical and psychosocial mediators that impact the successful reduction of pain among patients with EAP treated using rTMS. 5. to describe patients' perceptions of and satisfaction with rTMS as an intervention for EAP.

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 data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation for endometriosis pain?

Research suggests that Repetitive Transcranial Magnetic Stimulation (rTMS) may help reduce chronic pelvic pain in women with endometriosis, as nine out of twelve women in a pilot study reported improvements in pain and quality of life. Additionally, similar noninvasive brain stimulation techniques have shown significant pain reduction in endometriosis patients, indicating potential benefits of rTMS for managing this condition. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

In a pilot study with 12 women suffering from chronic pelvic pain due to endometriosis, repetitive transcranial magnetic stimulation (rTMS) was well tolerated, with no serious adverse effects reported. ^{1 2 6 7 8}

How does the treatment rTMS differ from other treatments for endometriosis pain?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, specifically targeting the primary motor cortex to reduce pain, which is different from traditional drug-based treatments. This non-invasive approach is particularly promising for patients whose pain has not been relieved by other treatments. ^{1 2 3 6 9}

Research Team

Linda McLean, PhD

Principal Investigator

University of Ottawa

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

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

Repetitive Transcranial Magnetic Stimulation Therapy (rTMS) for Endometriosis Patients with Refractory Pelvic Chronic Pain: A Pilot Study. [2020]

2. Australia pubmed.ncbi.nlm.nih.gov

Long-lasting analgesic effect of transcranial direct current stimulation in treatment of chronic endometriosis pain. [2017]

3. Switzerland 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. [2022]

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

Experimental pain tolerance is decreased and independent of clinical pain intensity in patients with endometriosis. [2019]

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

Effectiveness of neuromuscular electrical stimulation for endometriosis-related pain: A protocol of systematic review and meta-analysis. [2022]

6. England 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Role of medical treatment of endometriosis. [2021]

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

Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. [2022]