IPRP + rTMS for Chronic Pain

Overseen By Jillian V Miller, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Opioids

Disqualifiers: Developmental delay, Brain injury, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding brain stimulation to an intensive pain rehab program can better assist young people with severe chronic pain. Severe chronic pain lasts over three months and disrupts daily life. The trial will use repeated transcranial magnetic stimulation (rTMS) to target the brain area associated with pain. Participants will join an intensive rehab program, with or without brain stimulation, to compare outcomes. Youth aged 10-18 with severe pain affecting daily life, who have not improved with other treatments, might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could significantly enhance quality of life.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who need to wean off opioids. It's best to discuss your specific medications with the trial team.

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

Research has shown that Repeated Transcranial Magnetic Stimulation (rTMS) is generally safe and well-tolerated. Studies have found that rTMS does not cause harmful side effects. As a noninvasive treatment, it does not involve surgery or entering the body. rTMS has been safely used in young people with depression that doesn't respond to other treatments, suggesting it might also be safe for treating chronic pain in young people. Although specific data on using rTMS for chronic pain in youth is lacking, its use in other conditions supports its safety. ^{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 chronic pain because it offers a non-invasive approach that directly targets brain activity to alleviate pain. Unlike traditional treatments like medications or physical therapy, which often address symptoms more generally, rTMS leverages magnetic fields to stimulate specific areas of the brain associated with pain perception. This technique not only has the potential to provide relief without the side effects typical of pain medications, but it also offers a new avenue for understanding and treating pain at its neural roots.

What evidence suggests that this trial's treatments could be effective for chronic pain?

Research has shown that repeated transcranial magnetic stimulation (rTMS) may help treat chronic pain. One study found that rTMS significantly lowered pain levels compared to a placebo treatment. In adults, rTMS has effectively managed long-term pain, especially when targeting the dorsolateral prefrontal cortex (DLPFC), a brain area linked to pain and mental health. Another study suggested that rTMS can alleviate pain from various sources, such as nerve damage. Although primarily used in adults, these findings indicate that rTMS might also reduce chronic pain in young people. In this trial, participants in the "rTMS + IPRP" arm will receive rTMS as part of their treatment, while those in the "IPRP" arm will not receive the rTMS intervention. ^{1 2 6 7 8}

Who Is on the Research Team?

Jillian V Miller, PhD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for young people aged 10-18 with severe chronic pain that disrupts their daily life and hasn't improved with standard pain treatments. They must understand the importance of actively managing their condition to restore function, but can't join if they have significant developmental delays, brain injuries, need opioid weaning or have untreated psychiatric illnesses.

Inclusion Criteria

I and my family agree to actively manage my recovery.

My pain severely affects my daily life and stops me from doing my usual activities.

Pain treatments haven't helped me get back to my normal activities.

Exclusion Criteria

I have been diagnosed with a functional neurological disorder.

I am a young person needing help to stop using opioids.

I do not have severe medical or psychiatric conditions that would prevent rehabilitation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intensive Pain Rehabilitation Program (IPRP)

Participants undergo a three-week intensive day-treatment intervention provided by an interdisciplinary team to help resume engagement in normal daily functioning.

3 weeks

Daily visits (in-person)

Repeated Transcranial Magnetic Stimulation (rTMS)

Participants receive image-guided brain stimulation to enhance brain changes observed with IPRP, applied for 37.5 minutes per weekday.

3 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pain, functional disability, anxiety, depressive and PTSD symptoms.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Repeated Transcranial Magnetic Stimulation (rTMS)

Trial Overview

The study tests whether adding Repeated Transcranial Magnetic Stimulation (rTMS) to an Intensive Pain Rehabilitation Program (IPRP) helps reduce chronic pain in youth. The rTMS targets a specific brain area affected by chronic pain and is given daily for three weeks alongside IPRP.

How Is the Trial Designed?

Group I: rTMS + IPRP Experimental Treatment 2 Interventions

25 youth aged 10-18 years with severe chronic pain will be invited to partake in the Intensive Pain Rehabilitation Program, where they will receive Repeated Transcranial Magnetic Stimulation as one of their treatment interventions.

Group II: IPRP Active Control 1 Intervention

Youth within this arm will not be receiving the rTMS intervention. Rather, they will only be enrolled within the IPRP.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

In a study involving 13 participants, 1-Hz rTMS over the primary motor cortex (M1) was found to significantly increase subjective pain ratings and enhance neural responses (N2-P2 amplitudes) to acute pain induced by Adelta-fibers, suggesting that rTMS can amplify pain perception rather than alleviate it.

These findings, which show a correlation between increased pain ratings and enhanced neural activity, support the idea that rTMS over M1 has a complex relationship with pain perception, affecting both C-fiber and Adelta-fiber mediated pain responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation. Tamura, Y., Hoshiyama, M., Inui, K., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex significantly reduced pain levels in patients with drug-resistant neurogenic pain, showing a 22.9% reduction compared to only 7.8% with sham treatment, indicating its efficacy in pain management.

The effectiveness of rTMS was influenced by the origin and site of pain, with better outcomes for facial pain and poorer results in patients with brainstem strokes, suggesting that targeting adjacent cortical areas may be more beneficial than directly stimulating the painful zone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain. Lefaucheur, JP., Drouot, X., Menard-Lefaucheur, I., et al.[2022]

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]

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive alternative to electrical motor cortex stimulation (EMCS) for pain treatment, which requires surgery and may deter some patients.

The ongoing trial aims to improve the efficacy of rTMS by developing a convenient system for repeated treatments, targeting patients who respond positively to the initial rTMS sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive Transcranial Magnetic Stimulation for Intractable Pain]. Saitoh, Y.[2017]

High-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to effectively reduce chronic pain, supported by strong evidence of its analgesic effects.

Despite its efficacy, there is currently no standardized protocol for rTMS application, prompting the need for a practical algorithm to guide its use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical algorithm for using rTMS to treat patients with chronic pain. Lefaucheur, JP., Nguyen, JP.[2020]

In a case study of a 77-year-old woman with chronic neuropathic pain, high-frequency repetitive transcranial magnetic stimulation (rTMS) improved her quality of life, anxiety, depression, and walking ability, despite no change in pain intensity.

The results suggest that rTMS may enhance daily functioning in chronic pain patients by influencing brain circuits, indicating its potential therapeutic benefits beyond just pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic impact of motor cortex rTMS in patients with chronic neuropathic pain even in the absence of an analgesic response. A case report. Hodaj, H., Payen, JF., Lefaucheur, JP.[2018]

Prolonged continuous theta burst stimulation (pcTBS) over the primary motor cortex was found to be significantly more effective in providing analgesic effects compared to traditional high frequency rTMS (10 Hz), suggesting a promising new treatment for pain management.

The study involved 14 healthy volunteers and demonstrated that pcTBS not only has stronger analgesic effects but also requires a shorter treatment duration, making it a potentially more efficient option for clinical use, although further studies in patients are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged continuous theta-burst stimulation is more analgesic than 'classical' high frequency repetitive transcranial magnetic stimulation. Moisset, X., Goudeau, S., Poindessous-Jazat, F., et al.[2018]

In a pilot study involving 12 patients with therapy-resistant chronic pain, noninvasive repetitive transcranial magnetic stimulation (rTMS) of the motor cortex showed some analgesic effects, with 6 out of 6 patients reporting pain relief.

However, the overall difference in pain reduction between active rTMS and sham stimulation was not statistically significant, suggesting that further research with varied stimulation parameters is needed to better understand its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study. Rollnik, JD., Wüstefeld, S., Däuper, J., et al.[2017]

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pmc.ncbi.nlm.nih.gov

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Repetitive Transcranial Magnetic Stimulation in Chronic Pain

The decrease in pain scores with rTMS was 1.12 (95% confidence interval [CI] being 1.46–0.78) (fixed effects, I2 = 0%, P < 0.001) and in sham-rTMS was 0.28 (95% ...

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clinicaltrials.gov

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pmc.ncbi.nlm.nih.gov

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sciencedirect.com

sciencedirect.com/science/article/pii/S0361923025001959

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This study aimed to evaluate the therapeutic efficacy of rTMS in alleviating NP induced by chronic constriction injury (CCI) in a mouse model and to investigate ...

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