rTMS + Rehabilitation for Complex Regional Pain Syndrome

Overseen By Adam P Rufa, DPT, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: State University of New York - Upstate Medical University

Disqualifiers: Seizures, Epilepsy, Pacemaker, Pregnancy, others

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

Compensation: Varies

Number of Visits: 14

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Complex Regional Pain Syndrome (CRPS) Type 1, a condition causing long-lasting pain in an arm or leg. Participants will receive either real or sham (fake) repeated transcranial magnetic stimulation (rTMS), a method using magnets to stimulate the brain, combined with rehabilitation exercises. The researchers aim to determine if real rTMS reduces pain and improves function more effectively than the sham version. Individuals with CRPS in an arm or leg for at least six months and experiencing significant pain might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could lead to new treatment options 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, you cannot start any new treatments during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that repeated transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated. Studies have found that it can help reduce pain with only a few side effects. For instance, a review of several studies found that rTMS significantly reduced pain compared to a fake treatment. In another study, seven out of ten patients felt less pain after receiving rTMS.

Serious side effects rarely occur, indicating that rTMS is safe for most individuals. However, researchers are still studying its specific effects on complex regional pain syndrome (CRPS). Those considering joining a trial should discuss the possible risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of repeated Transcranial Magnetic Stimulation (rTMS) for treating Complex Regional Pain Syndrome (CRPS) because it offers a non-invasive way to directly target brain activity related to pain. Unlike standard treatments such as physical therapy, pain medications, or nerve blocks, rTMS uses magnetic fields to stimulate nerve cells in the brain, which could potentially recalibrate pain pathways and provide relief. This approach is particularly promising because it doesn't rely on drugs, minimizing side effects and offering an alternative for patients who haven't found relief through traditional methods. Additionally, the sham rTMS arm helps ensure that any benefits observed are truly due to the treatment itself rather than a placebo effect.

What evidence suggests that rTMS and rehabilitation could be effective for complex regional pain syndrome?

Research has shown that repeated transcranial magnetic stimulation (rTMS) can help with complex regional pain syndrome (CRPS). Early studies found that rTMS can reduce pain by 20–50% when targeted at the brain's movement control area. In one case, a person experienced a 90% reduction in pain and improved quality of life after long-term treatment. In this trial, participants will receive either rTMS or sham rTMS, both combined with best practice rehabilitation. rTMS is already used for conditions like nerve pain and depression, suggesting it could also benefit those with CRPS. Overall, rTMS shows promise in significantly reducing pain associated with CRPS. ^{2 6 7 8 9}

Who Is on the Research Team?

Adam Rufa, DPT, PhD

Principal Investigator

SUNY Upstate Medical Univerity

Are You a Good Fit for This Trial?

This trial is for individuals with CRPS Type 1, a pain condition affecting limbs, who've had it for at least 6 months. They must have stable treatment plans and moderate pain levels. It's not suitable for those with mental disorders preventing consent, non-English speakers, seizure history, metallic brain devices, pacemakers, or pregnant women.

Inclusion Criteria

I have had CRPS Type 1 in an arm or leg for at least 6 months.

I haven't started any new treatments, like medications or rehab, in the last 2 months.

My pain level is at least a 4 out of 10.

Exclusion Criteria

I have a history of seizures or epilepsy.

Intracranial metallic devices

Pacemaker

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either real or sham rTMS followed by rehabilitation over 4 weeks

4 weeks

10 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Surveys at 4 weeks, 3 months, 6 months, and 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Rehabilitation
• Repeated Transcranial Magnetic Stimulation
• Sham Repeated Transcranial Magnetic Stimulation

Trial Overview The study tests if repeated transcranial magnetic stimulation (rTMS) combined with rehabilitation can reduce pain in CRPS Type 1 patients. Participants are randomly assigned to real rTMS or sham (fake) rTMS plus rehab over four weeks to compare the effects on pain and physical function.

How Is the Trial Designed?

Group I: rTMS and Rehabilitation Experimental Treatment 2 Interventions

Subjects in this arm will get rTMS to the contralateral motor cortex and best practice rehabilitation.

Group II: Sham rTMS and Rehabilitation Placebo Group 2 Interventions

Subjects in this arm will get sham rTMS to the contralateral motor cortex and best practice rehabilitation.

Repeated Transcranial Magnetic Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Chronic pain
• Depression
• Anxiety disorders
• Complex Regional Pain Syndrome (CRPS)

Approved in European Union as rTMS for:

• Major depressive disorder
• Chronic pain
• Complex Regional Pain Syndrome (CRPS)

Approved in Canada as rTMS for:

• Major depressive disorder
• Chronic pain
• Complex Regional Pain Syndrome (CRPS)

Who Is Running the Clinical Trial?

State University of New York - Upstate Medical University

Lead Sponsor

Trials

176

Recruited

27,600+

Reflex Sympathetic Dystrophy Syndrome Association (RSDSA)

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In patients with complex regional pain syndrome type I (CRPS I), the motor cortical representation for the unaffected hand is significantly larger than for the affected hand, indicating altered sensory and motor processing in the brain.

This asymmetry in motor cortical representation was not observed in healthy subjects, suggesting that the condition affects how the brain maps motor control, potentially due to increased use of the unaffected hand and the influence of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Motor cortical representation in patients with complex regional pain syndrome: a TMS study]. Krause, P., Förderreuther, S., Straube, A.[2018]

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 21 patients with chronic complex regional pain syndrome, a 6-week graded motor imagery intervention significantly reduced movement pain and improved sensorimotor performance, highlighting its efficacy as a treatment.

The intervention was associated with positive changes in neurophysiological parameters, such as increased somatosensory hand representation and normalized intracortical inhibition, suggesting that graded motor imagery can modify underlying neural mechanisms related to chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graded motor imagery modifies movement pain, cortical excitability and sensorimotor function in complex regional pain syndrome. Strauss, S., Barby, S., Härtner, J., et al.[2021]

Repetitive magnetic stimulation (rMS) was tested in patients with complex regional pain syndrome (CRPS) and showed that their cortical motor evoked potentials (cMEP) were significantly smaller compared to healthy subjects, indicating altered brain responses to stimulation.

Unlike healthy individuals, CRPS patients did not exhibit a significant prolongation of the silent period after rMS, suggesting that their afferent input to the motor cortex is less effective, which may contribute to their pain condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of conditioning peripheral repetitive magnetic stimulation in patients with complex regional pain syndrome. Krause, P., Foerderreuther, S., Straube, A.[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]

In a study involving 27 patients with central and phantom limb pain, both low-frequency (1-Hz) and high-frequency (5-Hz) rTMS showed a temporary reduction in pain immediately after stimulation, but this effect was also seen with sham stimulation, indicating a placebo effect.

No significant long-term benefits were found for rTMS in reducing pain intensity or improving mood, leading to the conclusion that rTMS is not currently recommended as a standard treatment for these types of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Central and peripheral deafferent pain: therapy with repetitive transcranial magnetic stimulation]. Irlbacher, K., Kuhnert, J., Röricht, S., et al.[2018]

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. journals.lww.com journals.lww.com/aacr/fulltext/2024/04000/repetitive_transcranial_magnetic_stimulation_with.1.aspx

Repetitive Transcranial Magnetic Stimulation with... Previous reports in CRPS have shown a 31% decrease in pain catastrophizing after graded motor imagery and transcranial direct current stimualtion. 14 rTMS has ...

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

The effect of rTMS in the management of pain associated with ... Repetitive transcranial magnetic stimulation (rTMS) has analgesic effects on several types of pain. However, its effect on CRPS has not been elucidated clearly.

7. e-hpr.org e-hpr.org/journal/view.php?number=917

Efficacy and Safety of Repetitive Transcranial Magnetic ... Meta-analysis showed significant pain reduction with rTMS compared to sham treatment. At 2 weeks post-treatment, the mean pain score difference ...

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

Utilizing Repetitive Transcranial Magnetic Stimulation (rTMS ... Results: At one month, the patient reported a 30% reduction in total pain and increased overall quality of life, functional mobility, and independence. Average ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S030439400301365X

Repetitive transcranial magnetic stimulation of the motor ... Seven out of ten patients reported decreased pain intensities. Pain relief occurred 30 s after stimulation, whereas the maximum effect was found 15 min later.