Chronic Pain Clinical Trial
Official title:
Can Brain Stimulation Enhance Outcomes Associated With Intensive Rehabilitation for Youth With Chronic Pain?
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.
Status | Recruiting |
Enrollment | 25 |
Est. completion date | October 2026 |
Est. primary completion date | October 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 10 Years to 18 Years |
Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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. |
Country | Name | City | State |
---|---|---|---|
Canada | University of Calgary | Calgary | Alberta |
Lead Sponsor | Collaborator |
---|---|
University of Calgary |
Canada,
Bornhövd K, Quante M, Glauche V, Bromm B, Weiller C, Büchel C. Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. Brain. 2002 Jun;125(Pt 6):1326-36. — View Citation
Eccleston C, Palermo TM, Williams AC, Lewandowski Holley A, Morley S, Fisher E, Law E. Psychological therapies for the management of chronic and recurrent pain in children and adolescents. Cochrane Database Syst Rev. 2014 May 5;(5):CD003968. doi: 10.1002/14651858.CD003968.pub4. Review. Update in: Cochrane Database Syst Rev. 2018 Sep 29;9:CD003968. — View Citation
Fearon P, Hotopf M. Relation between headache in childhood and physical and psychiatric symptoms in adulthood: national birth cohort study. BMJ. 2001 May 12;322(7295):1145. — View Citation
Fox MD, Liu H, Pascual-Leone A. Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity. Neuroimage. 2013 Feb 1;66:151-60. doi: 10.1016/j.neuroimage.2012.10.082. Epub 2012 Nov 7. — View Citation
Garvey MA, Gilbert DL. Transcranial magnetic stimulation in children. Eur J Paediatr Neurol. 2004;8(1):7-19. Review. — View Citation
Glasser MF, Coalson TS, Robinson EC, Hacker CD, Harwell J, Yacoub E, Ugurbil K, Andersson J, Beckmann CF, Jenkinson M, Smith SM, Van Essen DC. A multi-modal parcellation of human cerebral cortex. Nature. 2016 Aug 11;536(7615):171-178. doi: 10.1038/nature18933. Epub 2016 Jul 20. — View Citation
Hechler T, Kanstrup M, Holley AL, Simons LE, Wicksell R, Hirschfeld G, Zernikow B. Systematic Review on Intensive Interdisciplinary Pain Treatment of Children With Chronic Pain. Pediatrics. 2015 Jul;136(1):115-27. doi: 10.1542/peds.2014-3319. Epub 2015 Jun 22. Review. — View Citation
Hogan ME, Taddio A, Katz J, Shah V, Krahn M. Incremental health care costs for chronic pain in Ontario, Canada: a population-based matched cohort study of adolescents and adults using administrative data. Pain. 2016 Aug;157(8):1626-33. doi: 10.1097/j.pain.0000000000000561. — View Citation
Hurtubise K, Blais S, Noel M, Brousselle A, Dallaire F, Rasic N, Camden C. Is It Worth It? A Comparison of an Intensive Interdisciplinary Pain Treatment and a Multimodal Treatment for Youths With Pain-related Disability. Clin J Pain. 2020 Nov;36(11):833-844. doi: 10.1097/AJP.0000000000000869. — View Citation
Kashikar-Zuck S, Flowers SR, Claar RL, Guite JW, Logan DE, Lynch-Jordan AM, Palermo TM, Wilson AC. Clinical utility and validity of the Functional Disability Inventory among a multicenter sample of youth with chronic pain. Pain. 2011 Jul;152(7):1600-1607. doi: 10.1016/j.pain.2011.02.050. Epub 2011 Mar 31. — View Citation
MacMaster FP, Croarkin PE, Wilkes TC, McLellan Q, Langevin LM, Jaworska N, Swansburg RM, Jasaui Y, Zewdie E, Ciechanski P, Kirton A. Repetitive Transcranial Magnetic Stimulation in Youth With Treatment Resistant Major Depression. Front Psychiatry. 2019 Mar 29;10:170. doi: 10.3389/fpsyt.2019.00170. eCollection 2019. — View Citation
Noel M, Vinall J, Tomfohr-Madsen L, Holley AL, Wilson AC, Palermo TM. Sleep Mediates the Association Between PTSD Symptoms and Chronic Pain in Youth. J Pain. 2018 Jan;19(1):67-75. doi: 10.1016/j.jpain.2017.09.002. Epub 2017 Sep 27. — View Citation
O'Reilly RC. The What and How of prefrontal cortical organization. Trends Neurosci. 2010 Aug;33(8):355-61. doi: 10.1016/j.tins.2010.05.002. Epub 2010 Jun 22. — View Citation
Perquin CW, Hazebroek-Kampschreur AAJM, Hunfeld JAM, Bohnen AM, van Suijlekom-Smit LWA, Passchier J, van der Wouden JC. Pain in children and adolescents: a common experience. Pain. 2000 Jul;87(1):51-58. doi: 10.1016/S0304-3959(00)00269-4. — View Citation
Sallet J, Mars RB, Noonan MP, Neubert FX, Jbabdi S, O'Reilly JX, Filippini N, Thomas AG, Rushworth MF. The organization of dorsal frontal cortex in humans and macaques. J Neurosci. 2013 Jul 24;33(30):12255-74. doi: 10.1523/JNEUROSCI.5108-12.2013. — View Citation
Seminowicz DA, Moayedi M. The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain. J Pain. 2017 Sep;18(9):1027-1035. doi: 10.1016/j.jpain.2017.03.008. Epub 2017 Apr 8. Review. — View Citation
Shelby GD, Shirkey KC, Sherman AL, Beck JE, Haman K, Shears AR, Horst SN, Smith CA, Garber J, Walker LS. Functional abdominal pain in childhood and long-term vulnerability to anxiety disorders. Pediatrics. 2013 Sep;132(3):475-82. doi: 10.1542/peds.2012-2191. Epub 2013 Aug 12. — View Citation
Simons LE, Pielech M, Erpelding N, Linnman C, Moulton E, Sava S, Lebel A, Serrano P, Sethna N, Berde C, Becerra L, Borsook D. The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome. Pain. 2014 Sep;155(9):1727-1742. doi: 10.1016/j.pain.2014.05.023. Epub 2014 May 23. — View Citation
Vinall J, Pavlova M, Asmundson GJ, Rasic N, Noel M. Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment. Children (Basel). 2016 Dec 2;3(4). pii: E40. Review. — View Citation
Zewdie E, Ciechanski P, Kuo HC, Giuffre A, Kahl C, King R, Cole L, Godfrey H, Seeger T, Swansburg R, Damji O, Rajapakse T, Hodge J, Nelson S, Selby B, Gan L, Jadavji Z, Larson JR, MacMaster F, Yang JF, Barlow K, Gorassini M, Brunton K, Kirton A. Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations. Brain Stimul. 2020 May - Jun;13(3):565-575. doi: 10.1016/j.brs.2019.12.025. Epub 2019 Dec 30. — View Citation
* Note: There are 20 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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). | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. | |
Primary | 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. |
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