IPRP Repeated Transcranial Magnetic Stimulation (rTMS)

NCT04561401 | Active Not Recruiting FDA Device

• 1 other identifier: REB20-1464
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Severe chronic pain is defined as pain persisting for three months or more that significantly impacts daily functioning. It is highly prevalent, occurring in 100,000 to 160,000 youth. If left unmanaged it can lead to persistent pain and mental health problems in adulthood, posing enormous costs to society ($7.2 billion CAD/year). In 2014, health professionals at the Alberta Children's Hospital (ACH) established a pediatric Intensive Pain Rehabilitation Program (IPRP) to target youth with severe chronic pain and consequent functional disability who do not respond to outpatient pain therapies. The IPRP at the ACH is a three-week intensive day-treatment intervention provided by an interdisciplinary team, which helps youth resume engagement in normal daily functioning. Following IPRP, youth reported less anxiety, less depressive symptoms, and greater function, although their self-reported pain remained unchanged. In August 2016, the investigators began to explore brain areas related to severe chronic pain in youth. The investigators scanned a subset of youth at the start (baseline) and end (discharge) of IPRP (23 youth with 2 brain scans). From baseline to discharge, the investigators saw decreases in activity in the dorsolateral prefrontal cortex (DLPFC). Decrease in DLPFC activity was related to better mental health outcomes. The DLPFC is a well-known target for non-invasive brain stimulation. Repeated brain stimulation has been used to treat adults, but not youth with chronic pain. For the first time, the investigators will use image-guided brain stimulation (37 minutes/day, 5 days/week) to enhance the brain changes observed with IPRP. The investigators will examine whether three weeks of brain stimulation helps to reduce pain symptoms in youth. The investigators will also compare pain, brain, and mental health outcomes to our historical program data. By adding brain stimulation to our pain intervention, the investigators have the chance to target an area of the brain investigators know to be altered by chronic pain to improve outcomes.

Conditions

Chronic Pain

Outcome Measures

Primary Outcomes (21)

• Pain Presence

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at baseline.

• Pain Frequency

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at baseline.

• Pain Duration

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at baseline.

• Pain Intensity

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at baseline.

• Pain Interference

  Youth will complete the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile-25. The Pain Interference subscale uses 4 items to assess whether pain has interfered with youth's everyday activities in the past 7 days using a 5-point Likert scale (anchors: 0 = "never" and 4 = "almost always"). The PROMIS measures demonstrated good construct validity (intercept and slope equal or greater to 0.98) and internal consistency (pain interference, 4 items alpha = 0.85).

  This outcome will be measured at baseline.

• Brain imaging

  Structural and functional imaging will be acquired using resting-state functional magnetic resonance imaging (fMRI) scan. Motion will be censored using the Artifact Detection Tools (ART). Cortical masks derived from FreeSurfer will be used as seed regions for fMRI functional connectivity analysis. Time courses for the dorsolateral prefrontal cortex (DLPFC) will be extracted and used as a regressor to identify correlations with all other brain regions. Second-level analyses will be used to test differences in functional connectivity over time and between groups. All statistical tests will be corrected for multiple comparisons.

  This outcome will be measured at baseline (upon admittance into the program).

• Functional disability

  The Functional Disability Inventory (FDI) will be administered to assess functional disability. Youth will rate their level of difficulty in completing daily activities in a variety of settings (e.g. home, school) on a 5-point Likert scale ranging from 0 "no trouble" to 4 "impossible." Higher scores are indicative of greater pain-related disability. The FDI has high internal consistency at baseline (alpha = .90) and post-treatment (alpha = .87).

  This outcome will be measured at baseline.

• Anxiety and Depressive Symptoms

  Anxiety and depressive symptoms will be assessed using the PROMIS Pediatric Profile-25 Anxiety and Depression subscales. Participants will report if they experienced any of the symptoms in the past 7 days using a 5-point Likert scale (anchors: 0 = "never" and 4 = "almost always"). The subscales have demonstrated good construct validity (intercept and slope equal to or greater than 0.93) and excellent internal consistency (depressive symptoms, 4 items, alpha = 0.91; anxiety symptoms, 4 items, alpha = 0.90).

  This outcome will be measured at baseline.

• Posttraumatic Stress Disorder (PTSD) Symptoms

  Youth PTSD symptomology will be assessed using the Child PTSD Symptom Scale (CPSS-V). The CPSS-V is a 20-item measure that maps on to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition PTSD criteria, and assessed PTSD symptoms experienced by youth in the past month. Youth will be asked to identify something scary or upsetting that bothers them to think about. With that event in mind, they will be asked to respond to 20 items assessing PTSD symptoms on a 5-point Likert scale, ranging from "not at all" to "6 or more times a week/almost always." Total symptom severity scores are obtained by summing the 20 items (range: 0-80). A score of 31 or above indicates clinically elevated PTSD symptoms. The CPSS-V has excellent internal consistency, good test-retest reliability, and good convergent validity.

  This outcome will be measured at baseline.

• Pediatric Transcranial Magnetic Stimulation (TMS) Safety and Tolerability

  Possible adverse events (headache, presyncope, nausea, etc.) will be screened and quantified as either mild, moderate, or severe. Any other potential side effects will be recorded and quantified.

  This outcome will be measured at Day 1.

• Pain Presence

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Pain Frequency

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Pain Duration

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Pain Intensity

  The commonly used Pain Questionnaire will be administered to measure the presence and characteristics of pain. Youth will rate the average frequency ("not at all" to "daily"), duration ("less than 1 hour" to "all day"), and intensity ("no pain" to "worst pain possible") of their pain.

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Pain Interference

  Youth will complete the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile-25. The Pain Interference subscale uses 4 items to assess whether pain has interfered with youth's everyday activities in the past 7 days using a 5-point Likert scale (anchors: 0 = "never" and 4 = "almost always"). The PROMIS measures demonstrated good construct validity (intercept and slope equal or greater to 0.98) and internal consistency (pain interference, 4 items alpha = 0.85).

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Brain imaging

  Structural and functional imaging will be acquired using resting-state functional magnetic resonance imaging (fMRI) scan. Motion will be censored using the Artifact Detection Tools (ART). Cortical masks derived from FreeSurfer will be used as seed regions for fMRI functional connectivity analysis. Time courses for the dorsolateral prefrontal cortex (DLPFC) will be extracted and used as a regressor to identify correlations with all other brain regions. Second-level analyses will be used to test differences in functional connectivity over time and between groups. All statistical tests will be corrected for multiple comparisons.

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Functional disability

  The Functional Disability Inventory (FDI) will be administered to assess functional disability. Youth will rate their level of difficulty in completing daily activities in a variety of settings (e.g. home, school) on a 5-point Likert scale ranging from 0 "no trouble" to 4 "impossible." Higher scores are indicative of greater pain-related disability. The FDI has high internal consistency at baseline (alpha = .90) and post-treatment (alpha = .87).

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Anxiety and Depressive Symptoms

  Anxiety and depressive symptoms will be assessed using the PROMIS Pediatric Profile-25 Anxiety and Depression subscales. Participants will report if they experienced any of the symptoms in the past 7 days using a 5-point Likert scale (anchors: 0 = "never" and 4 = "almost always"). The subscales have demonstrated good construct validity (intercept and slope equal to or greater than 0.93) and excellent internal consistency (depressive symptoms, 4 items, alpha = 0.91; anxiety symptoms, 4 items, alpha = 0.90).

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Posttraumatic Stress Disorder (PTSD) Symptoms

  Youth PTSD symptomology will be assessed using the Child PTSD Symptom Scale (CPSS-V). The CPSS-V is a 20-item measure that maps on to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition PTSD criteria, and assessed PTSD symptoms experienced by youth in the past month. Youth will be asked to identify something scary or upsetting that bothers them to think about. With that event in mind, they will be asked to respond to 20 items assessing PTSD symptoms on a 5-point Likert scale, ranging from "not at all" to "6 or more times a week/almost always." Total symptom severity scores are obtained by summing the 20 items (range: 0-80). A score of 31 or above indicates clinically elevated PTSD symptoms. The CPSS-V has excellent internal consistency, good test-retest reliability, and good convergent validity.

  This outcome will be measured at discharge from the program, which is approximately 3 weeks from the time of admittance.

• Pediatric Transcranial Magnetic Stimulation (TMS) Safety and Tolerability

  Possible adverse events (headache, presyncope, nausea, etc.) will be screened and quantified as either mild, moderate, or severe. Any other potential side effects will be recorded and quantified.

  This outcome will be measured at Day 6.

• Pediatric Transcranial Magnetic Stimulation (TMS) Safety and Tolerability

  Possible adverse events (headache, presyncope, nausea, etc.) will be screened and quantified as either mild, moderate, or severe. Any other potential side effects will be recorded and quantified.

  This outcome will be measured at Day 11.

Study Arms (2)

rTMS + IPRP

EXPERIMENTAL

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.

Device: Repeated Transcranial Magnetic Stimulation (rTMS); Other: Intensive Pain Rehabilitation Program (IPRP)

IPRP

ACTIVE COMPARATOR

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

Other: Intensive Pain Rehabilitation Program (IPRP)

Interventions

Repeated Transcranial Magnetic Stimulation (rTMS) DEVICE

rTMS will be applied at 10 Hz. Each train will consist of 40 supra threshold (120% resting motor threshold) pulses over 4 seconds with an inter-train interval of 26 seconds. Treatment sessions will last 37.5 minutes (75 trains/3,000 pulses), and occur at the same time of day on every weekday for a period of three weeks (15 days total). During TMS, only passive activities will be allowed (i.e., watching movies or TV, listening to music). Three weeks of treatment was selected based on existing rTMS evidence in youth with treatment resistant major depressive disorder.

rTMS + IPRP

Intensive Pain Rehabilitation Program (IPRP) OTHER

The paediatric Intensive Pain Rehabilitation Program (IPRP) in Canada was established to target youth with severe chronic pain and consequent functional disability who do not respond to standard outpatient pain therapies. The IPRP at the Alberta Children's Hospital (ACH) involves three- to six-weeks of day-treatment rehabilitation, provided by an interdisciplinary team (e.g. Psychology, Physiotherapy, Family Therapy). This rehabilitative program teaches self-management strategies with the goal of helping youth and their families resume normal daily functioning.

IPRP; rTMS + IPRP

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Between the ages of 10-18 years
• Patient has had the appropriate medical work-up
• Participation in accessible, evidenced based pain therapies has not demonstrated return to functional goals
• Pain is significantly impacting the patient's life and they are not meeting their functional goals in areas of life, which may include: physical function, sleep, self-care, school attendance/academic performance, social function, recreational engagement, and mood
• Patient and family agree and understand that an active, self-management approach to functional restoration is the mainstay of treatment in the IPRP

You may not qualify if:

• Significant developmental delay or brain injury
• Functional neurological disorder/conversion disorder
• Youth who require opioid weaning
• Extensive medical needs and/or untreated psychiatric illness that would impede a rehabilitative approach to care.

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T3B 6A8, Canada

Location

Related Publications (20)

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MeSH Terms

Conditions

Chronic Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jillian V Miller, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 11, 2020
• First Posted: September 23, 2020
• Study Start: October 19, 2020
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)