TMS for Complex Regional Pain Syndrome

Overseen By Birute Gedrimaite

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Epilepsy, Psychiatric disorder, Neurologic illness, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether Transcranial Magnetic Stimulation (TMS), which uses magnetic fields to stimulate nerve cells, can effectively reduce pain and other symptoms in people with Complex Regional Pain Syndrome (CRPS). The study includes two groups: one receives active TMS, while the other receives a sham (inactive) treatment, both administered once daily for two days. Researchers monitor participants to determine if symptoms improve and how long those improvements last. Suitable candidates for this trial are individuals diagnosed with CRPS for over three months who experience significant daily pain. As an unphased trial, this study provides a unique opportunity to explore a promising treatment option for CRPS.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if your medication use interferes with the study procedures or data integrity, the researcher may decide it is necessary.

What prior data suggests that TMS is safe for treating Complex Regional Pain Syndrome?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe and well-tolerated. It already treats depression by targeting specific brain areas. Studies have found that TMS can also effectively treat pain linked to Complex Regional Pain Syndrome (CRPS).

Most patients handle TMS well, experiencing only minor side effects. Some may feel mild discomfort during the procedure, such as tingling or scalp sensitivity. Overall, TMS shows promise as a safe and effective way to manage CRPS symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Transcranial Magnetic Stimulation (TMS) is unique because it targets the brain's pain-processing areas without the need for surgery or medication. Unlike standard treatments for Complex Regional Pain Syndrome, which often involve medication or invasive procedures, TMS uses magnetic fields to stimulate nerve cells, potentially offering a non-invasive and drug-free alternative. Researchers are excited about TMS because it may offer quicker relief and fewer side effects compared to traditional options, and it has the potential to be effective even in cases where other treatments have failed.

What evidence suggests that TMS might be an effective treatment for CRPS?

Research has shown that Transcranial Magnetic Stimulation (TMS) can help reduce pain in people with Complex Regional Pain Syndrome (CRPS). Early studies indicate that TMS can lower pain levels by 20-50% for some patients. One study reported a patient experiencing a 90% reduction in symptoms, including pain, after about 140 days. In this trial, participants will receive either active TMS in the target area or a sham treatment in a non-target area. TMS is already used to treat conditions like depression and certain types of pain, suggesting it could also be helpful for CRPS. It is important to note that TMS is an add-on therapy, used alongside other treatments for better results. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with Complex Regional Pain Syndrome (CRPS) for at least 3 months, who can perform required tasks and have a certain level of pain. It's not for those with psychological disorders, medical conditions or medications that affect the study, pregnant women, people in legal/disability claims, TMS contraindications like metal implants near stimulation site, epilepsy sufferers or those with MRI contraindications.

Inclusion Criteria

I can do the tasks and procedures required in the study.

I have been diagnosed with CRPS for at least 3 months.

My pain level matches the study's required range.

Exclusion Criteria

Currently pregnant or planning to become pregnant

Current medical condition or medication use that would interfere with study procedures or data integrity, at the discretion of the researcher

I do not have any brain conditions that affect its function.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TMS or sham treatment once daily for two days

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment until they reach baseline for two consecutive weeks

up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• TMS

Trial Overview The trial tests if Transcranial Magnetic Stimulation (TMS) can reduce CRPS-related pain and improve cognitive, emotional and physical symptoms. Participants are divided into two groups: one receives TMS while the other gets sham treatment daily for two days. Their progress is monitored until they return to baseline pain levels for two weeks.

How Is the Trial Designed?

Group I: Active Treatment Experimental Treatment 1 Intervention

Participants will receive active TMS in the target area once daily for two days

Group II: Sham Treatment Placebo Group 1 Intervention

Participants will receive active TMS in a non-target area once daily for two days

TMS is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in European Union as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in Canada as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Rocky Mountain Foundation

Collaborator

Trials

1

Recruited

40+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Redlich Pain Endowment

Collaborator

Trials

1

Recruited

40+

The Feldman Family Foundation Pain Research Fund

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

In a study involving 23 patients with complex regional pain syndrome (CRPS) type I, 10 daily sessions of real repetitive transcranial magnetic stimulation (rTMS) significantly reduced pain levels, with a mean reduction of 4.65 cm on the Visual Analog Scale (VAS), compared to only 2.18 cm in the sham group.

The rTMS treatment not only alleviated pain but also improved emotional and affective aspects of pain, suggesting that repeated sessions of high-frequency rTMS could be an effective add-on therapy for patients with refractory CRPS type I.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I. Picarelli, H., Teixeira, MJ., de Andrade, DC., et al.[2022]

In a study of 11 patients with complex regional pain syndrome (CRPS), repetitive transcranial magnetic stimulation (rTMS) targeting the motor cortex led to an average 22% reduction in pain scores, with 55% of participants meeting the criteria for a significant response.

The study revealed a functional connection between pain perception and autonomic responses, as evidenced by changes in electrochemical skin conductance (ESC) and brain activation in specific regions, suggesting potential new targets for CRPS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural Correlates of Pain-Autonomic Coupling in Patients With Complex Regional Pain Syndrome Treated by Repetitive Transcranial Magnetic Stimulation of the Motor Cortex. Delon-Martin, C., Lefaucheur, JP., Hodaj, E., et al.[2023]

In a study of 80 patients with chronic central neuropathic pain, repetitive transcranial magnetic stimulation (rTMS) showed significant pain relief, with an average reduction of 28% after the first 4 sessions and a cumulative effect of 48% after 15 sessions over 12 months.

The treatment was safe, with over 1000 rTMS sessions administered without any adverse effects, indicating its potential as a long-term therapy for refractory central neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-Guided Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Central Neuropathic Pain. Quesada, C., Pommier, B., Fauchon, C., et al.[2019]

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]

In a study of 63 obese individuals undergoing a 5-week rTMS treatment for weight control, the treatment showed a reassuring safety profile with no unexpected adverse events reported up to one year after treatment.

The most common side effects were moderate headaches (40.4%) and local pain/discomfort (19.2%), particularly more frequent in the high-frequency rTMS group, but overall, rTMS was well tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. Ferrulli, A., Massarini, S., Macrì, C., et al.[2021]

In a study of 10 patients with complex regional pain syndrome (CRPS), repetitive transcranial magnetic stimulation (rTMS) significantly reduced pain intensity, with effects starting just 30 seconds after stimulation and peaking at 15 minutes.

Unlike sham rTMS, which had no effect, the results suggest that rTMS can effectively modulate pain perception in CRPS, indicating a potential therapeutic approach for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I. Pleger, B., Janssen, F., Schwenkreis, P., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to provide significant pain relief in chronic pain conditions, particularly with high-frequency stimulation over the primary motor cortex, achieving over 30% pain reduction compared to control treatments.

Despite the promising results, most studies did not utilize repetitive rTMS sessions, indicating a need for further research to explore the long-term effects and optimal treatment protocols for various chronic pain syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature. Galhardoni, R., Correia, GS., Araujo, H., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Transcranial Magnetic Stimulation (TMS) showed significant pain relief in patients with Complex Regional Pain Syndrome (CRPS) affecting both upper and lower extremities, with 60% of participants experiencing at least a 30% reduction in pain after a single session.

The TMS protocol was safe, with no serious adverse events reported, although common side effects included headache and nausea; careful monitoring is recommended to prevent potential seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing Transcranial Magnetic Stimulation Methods for Complex Regional Pain Syndrome: An Open-Label Study of Paired Theta Burst and High-Frequency Stimulation. Gaertner, M., Kong, JT., Scherrer, KH., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment that can provide partial and temporary relief from severe chronic pain, particularly in conditions like neuropathic pain and fibromyalgia.

While rTMS effects are generally short-lived, daily sessions over several weeks can lead to longer-lasting pain relief, and for patients who respond but later relapse, surgical options like implanted electrodes may help maintain the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of repetitive transcranial magnetic stimulation in pain relief. Lefaucheur, JP.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11760760/

Repetitive Transcranial Magnetic Stimulation for the Treatment ... For CRPS, data is limited, but initial studies demonstrate that rTMS delivered over M1 is effective at reducing pain by 20–50%. One study ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S305052912500087X

Use of deep repetitive transcranial magnetic (dTMS ... Long-term follow-up assessment (at 140 days) revealed 90 % alleviation of most of her symptoms including pain. It also resulted in better quality of her life.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05197959

Treatment of Complex Regional Pain Syndrome This study will investigate the feasibility of using repetitive transcranial magnetic stimulation (rTMS) and a sensorimotor training task to treat symptoms ...

4. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(23)00615-0/fulltext

Repetitive transcranial magnetic stimulation (rTMS) for ... Repetitive transcranial magnetic stimulation (rTMS) is in clinical use for eg neuropathic pain, stroke rehabilitation, and depression.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20430702/

Repetitive transcranial magnetic stimulation is efficacious ... This study shows an efficacy of repetitive sessions of high-frequency rTMS as an add-on therapy to refractory CRPS type I patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7711855/

The effect of rTMS in the management of pain associated with ... Based on the results of this meta-analysis, we propose that rTMS can be a good treatment option for pain associated with CRPS.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03137472

NCT03137472 | TMS for Complex Regional Pain Syndrome Participants will be followed until they reach their baseline for two consecutive weeks to assess safety and duration of symptom alleviation. Official Title.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6033652/

An Open-Label Study of paired theta burst and high ... TMS is generally safe and well-tolerated (10), and stimulation of prefrontal cortex is used clinically to treat depression (11).

9. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(21)00166-2/fulltext

Utilizing Repetitive Transcranial Magnetic Stimulation ... rTMS may be a safe, tolerable, and effective treatment for individuals with refractory and widespread CRPS.