Repetitive Transcranial Magnetic Stimulation for Endometriosis Pain
Recruiting in Palo Alto (17 mi)
Overseen byLinda McLean, PhD
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Ottawa
Disqualifiers: Epilepsy, Pregnancy, Infections, others
No Placebo Group
Approved in 4 Jurisdictions
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.
12345Is 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.
12678How 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.
12369Eligibility 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.
+2 more
Trial 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
Participant Groups
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).
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Real RepetitiveTranscranial Magnetic Stimulation (rTMS) 5 sessionsExperimental Treatment1 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 sessionsExperimental Treatment1 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 sessionsPlacebo Group1 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 sessionsPlacebo Group1 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, Australia 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
🇦🇺 Approved in Australia as rTMS for:
- Major depressive disorder
- Obsessive-compulsive disorder
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McLean Function Measurement LabOttawa, Canada
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Who Is Running the Clinical Trial?
University of OttawaLead Sponsor
References
Repetitive Transcranial Magnetic Stimulation Therapy (rTMS) for Endometriosis Patients with Refractory Pelvic Chronic Pain: A Pilot Study. [2020]Endometriosis concerns more than 10% of women of reproductive age, frequently leading to chronic pelvic pain. Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) induces an analgesic effect. This effect on chronic pelvic pain is yet to be evaluated. 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 pain due to endometriosis. This pilot, open-labelled prospective trial examined treatment by neuronavigated rTMS over M1, one session per day for 5 consecutive days. Each session consisted of 1.500 pulses at 10 Hz. We assessed tolerance, pain change and QoL until 4 weeks post treatment with a primary endpoint at day 8. Twelve women were included. No patients experienced serious adverse effects or a significant increase in pain. Nine women reported improvement on the Patient Global Impression of Change with a reduction in both pain intensity and pain interference (5.1 ± 1.4 vs. 4.1 ± 1.6, p = 0.01 and 6.2 ± 2.1 vs. 4.2 ± 1.5, p = 0.004, respectively). rTMS appears well tolerated and might be of interest for patients suffering from chronic pelvic pain for whom other treatments have failed. A randomized controlled trial is mandatory before proposing such treatment.
Long-lasting analgesic effect of transcranial direct current stimulation in treatment of chronic endometriosis pain. [2017]Approximately 10-20% of women of reproductive age suffer from endometriosis, with 70-90% of these women reporting chronic pain symptoms that persist during their menstrual cycle. We are presenting a case in which a novel form of noninvasive brain stimulation called transcranial direct current stimulation was used as an intervention in a 32-year-old woman with persistent, chronic pain symptoms caused by endometriosis for 20 years. Ten daily, 20-min sessions of 2-mA anodal transcranial direct current stimulation were applied over the left primary motor cortex. Acutely, visual analog scale pain symptoms were reduced by 60%. There were also significant decreases in modules of the Endometriosis Health Profile. At the 4-month follow-up, the patient still expressed an overall decrease in pain symptoms of 30%.
When Two Is Better Than One: A Pilot Study on Transcranial Magnetic Stimulation Plus Muscle Vibration in Treating Chronic Pelvic Pain in Women. [2022]Chronic pelvic pain syndrome (CPPS) affects about 4-16% of adult women, and about one-third of them require medical assistance due to severe symptoms. Repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) has been shown to manage pain in refractory CPPS. Focal muscle vibration (FMV) has also been reported to relieve pelvic pain. The objective of this study was to assess the feasibility and effect of rTMS coupled with FMV to reduce pain in seven adult women with refractory CPPS. This pilot, open-labeled, prospective trial examined treatment by 5 Hz rTMS over SMA and 150 Hz FMV over the perineum, suprapubic, and sacrococcygeal areas, with one daily session for five consecutive days for three weeks. We assessed tolerance and subjective pain changes (as per visual analog scale, VAS) until one month post-treatment, with a primary endpoint at day 7. No patients experienced serious adverse effects or a significant increase in pain. Six out of seven patients experienced a VAS improvement of at least 10% at T7; three of these individuals experienced a VAS improvement of more than 30%. Overall, we found a significant VAS reduction of 15 points (95% CI 8.4-21.6) at T7 (t = 6.3, p = 0.001; ES = 2.3 (1.1-3.9)). Three of the women who demonstrated a significant VAS reduction at T7 retained such VAS improvement at T30. VAS decreased by six points (95% CI 1.3-10.7) at T30 (t = 3.1, p = 0.02; ES = 1.5 (0.2-2.6)). This coupled approach seems promising for pain management in adult women with refractory CPPS and paves the way for future randomized controlled trials.
Experimental pain tolerance is decreased and independent of clinical pain intensity in patients with endometriosis. [2019]To investigate alterations in tactile, pain thresholds and pain tolerance thresholds in patients with endometriosis using a multimodality approach.
Effectiveness of neuromuscular electrical stimulation for endometriosis-related pain: A protocol of systematic review and meta-analysis. [2022]This study will assess the effectiveness and safety of neuromuscular electrical stimulation (NMES) for endometriosis-related pain (ERP).
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]Nearly one in seven women worldwide suffers from chronic pelvic pain syndrome (CPPS) each year. Often, CPPS necessitates a combination of treatments. Studies have shown the good therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) upon CPPS. We wish to undertake a randomized controlled trial (RCT) to observe the effect of high-frequency rTMS at different intensities upon CPPS.
Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. [2022]A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain.
Role of medical treatment of endometriosis. [2021]Endometriosis is a chronic benign disease that affects women of reproductive age. Medical therapy is often the first line of management for women with endometriosis in order to ameliorate symptoms or to prevent post-surgical disease recurrence. Currently, there are several medical options for the management of patients with endometriosis and long-term treatments should balance clinical efficacy (controlling pain symptoms and preventing recurrence of disease after surgery) with an acceptable safety-profile. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of chronic inflammatory conditions, being efficacious in relieving primary dysmenorrhea. Combined oral contraceptives and progestins, available for multiple routes of administration, are commonly administered as first-line hormonal therapies. Several studies demonstrated that they succeed in improving pain symptoms in the majority of patients; moreover, they are well tolerated and not expensive. Gonadotropin-releasing hormone-agonists are prescribed when first line therapies are ineffective, not tolerated or contraindicated. Even if these drugs are efficacious in treating women not responding to COCs or progestins, they are not orally available and have a less favorable tolerability profile (needing an appropriate add-back therapy). Because few data are available on long-term efficacy and safety of aromatase inhibitors they should be reserved only for women with symptoms who are refractory to other treatments only in a research environment. Almost all of the currently available treatment options for endometriosis suppress ovarian function and are not curative. For this reason, research into new drugs is unsurprisingly demanding. Amongst the drugs currently under investigation, gonadotropin-releasing hormone antagonists have shown most promise, currently in late-stage clinical development. There is a number of potential future therapies currently tested only in vitro, in animal models of endometriosis or in early clinical studies with a small sample size. Further studies are necessary to conclude whether these treatments would be of value for the treatment of endometriosis.
Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. [2022]Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.