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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment rTMS + Rehabilitation for Complex Regional Pain Syndrome?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce pain in patients with complex regional pain syndrome (CRPS), with significant pain relief reported in several studies. Additionally, combining rTMS with rehabilitation therapies like physical and occupational therapy may enhance overall treatment effectiveness by addressing both pain and functional recovery. ^{1 2 3 4 5}

Is rTMS safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) has been studied in humans for conditions like complex regional pain syndrome (CRPS) and has shown to be generally safe, with no significant adverse effects reported in the studies. It involves using magnetic fields to stimulate nerve cells in the brain, and while it can cause mild discomfort or headaches, serious side effects are rare. ^{1 2 3 5 6}

How does the treatment rTMS differ from other treatments for complex regional pain syndrome?

rTMS (repeated transcranial magnetic stimulation) is unique because it uses magnetic fields to stimulate the brain's motor cortex, which can reduce pain perception in complex regional pain syndrome. Unlike traditional medications, rTMS directly targets brain activity and has shown to provide pain relief shortly after treatment, with effects lasting for a limited time. ^{1 2 3 4 5}

What is the purpose of this trial?

Subjects with complex regional pain syndrome (CRPS) Type 1 will be randomized to receive repeated transcranial magnetic stimulation (rTMS) followed by rehabilitation or sham rTMS followed by rehabilitation. Treatment will last for 4 weeks, with the first week including 4 rTMS treatments and 2 rehabilitation treatments. Subsequent weeks will include 2 rTMS treatments followed by 2 rehabilitation treatments. Outcome measures will include pain ratings, PROMIS questionnaires, global rating of change, and grip strength or 1 repetition maximum leg press.

Research Team

Adam Rufa, DPT, PhD

Principal Investigator

SUNY Upstate Medical Univerity

Eligibility Criteria

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.

No plan to initiate a new intervention during the study treatment timeframe (4 weeks)

Exclusion Criteria

I have a history of seizures or epilepsy.

Intracranial metallic devices

Pacemaker

Timeline

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

Treatment Details

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.

Participant Groups

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+

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]

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 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]

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 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]

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. England pubmed.ncbi.nlm.nih.gov

Effects of conditioning peripheral repetitive magnetic stimulation in patients with complex regional pain syndrome. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Graded motor imagery modifies movement pain, cortical excitability and sensorimotor function in complex regional pain syndrome. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

[Motor cortical representation in patients with complex regional pain syndrome: a TMS study]. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

[Central and peripheral deafferent pain: therapy with repetitive transcranial magnetic stimulation]. [2018]