TMS for Complex Regional Pain Syndrome

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stanford University

Disqualifiers: Epilepsy, Psychiatric disorder, Neurologic illness, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new method that uses magnetic pulses to influence brain activity. It aims to help people with a difficult-to-treat chronic pain condition by reducing pain and improving symptoms. This method has been used in various conditions, including depression, Parkinson's disease, Alzheimer's disease, and chronic pain.

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 data supports the effectiveness of the treatment for Complex Regional Pain Syndrome?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce pain in people with Complex Regional Pain Syndrome (CRPS). In one study, 7 out of 10 patients reported less pain after rTMS, and another study found significant pain reduction in patients receiving rTMS compared to a placebo treatment. ^{1 2 3 4 5}

Is Transcranial Magnetic Stimulation (TMS) safe for humans?

Transcranial Magnetic Stimulation (TMS), including its repetitive form (rTMS), has been used safely in both healthy individuals and those with various conditions since the 1990s. Safety guidelines have been established and updated over the years, with most studies showing a reassuring safety profile, including in conditions like obesity. Common safety considerations include screening for risks and monitoring for any adverse events. ^{1 3 6 7 8}

How does the treatment TMS differ from other treatments for Complex Regional Pain Syndrome?

Transcranial Magnetic Stimulation (TMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate nerve cells in the brain, specifically targeting the motor cortex to reduce pain perception. Unlike traditional medications, TMS provides short-term pain relief and can be used as an add-on to existing therapies, offering a novel approach for patients who do not respond well to standard treatments. ^{1 2 3 9 10}

Research Team

Eligibility Criteria

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

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

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

Trial Timeline

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

Treatment Details

Interventions

• TMS (Non-invasive Brain Stimulation)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Rocky Mountain Foundation

Collaborator

Trials

1

Recruited

40+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

Redlich Pain Endowment

Collaborator

Trials

1

Recruited

40+

The Feldman Family Foundation Pain Research Fund

Collaborator

Trials

1

Recruited

40+

Findings from Research

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]

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]

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]

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]

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]

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) 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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I. [2019]

2. United States 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. [2022]

3. United States 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. [2022]

4. United States 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. [2023]

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

Robot-Guided Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Central Neuropathic Pain. [2019]

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

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

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

Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature. [2022]

10. England pubmed.ncbi.nlm.nih.gov

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