Clinical trial NCT05986370: The METRIC Study Protocol
Official title: The METRIC Study Protocol: an Explanatory Randomized Controlled Trial Investigating the Neurophysiological Mechanisms Underlying the Therapeutic Effects of Spinal Manipulative Therapy for Chronic Primary Low Back Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Low-back Pain
Keywords: chronic primary low back pain
spinal manipulative therapy
nociplastic pain
central sensitization
C-fibers
brain
electroencephalography
Lead sponsor: Université du Québec à Trois-Rivières
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test the effects of spinal manipulative therapy in individuals with chronic primary low back pain and determine the neurophysiological mechanisms underlying pain relief. The main questions it aims to answer are: • Is pain relief produced by spinal manipulative therapy in patients with chronic primary low back pain caused by a reduction of C-fiber-related nociceptive processing? • Are these effects greater when spinal manipulative therapy is applied to the whole spine where it is clinically indicated compared with lumbar spine only? • Are these effects greater after 36 treatments over 3 months compared with 12 treatments over 1 month. Participants will receive spinal manipulative therapy (all clinically indicated spine segments or back only) or a control intervention. A group of healthy volunteers will be recruited to assess secondary outcome measures over the same time period, as reference data for comparisons. Researchers will compare the two groups receiving spinal manipulative therapy to the group receiving the control intervention to see if clinical pain relief and the reduction of temporal summation of second pain (produced experimentally) is significantly greater with spinal manipulative therapy.


Eligibility criteria: Inclusion Criteria:

* Duration of current low back pain (LBP) episode ≥ 6 months;
* Average LBP intensity during the last 7 days ≥ 3/10;
* (For healthy volunteers only) To be of the same sex and age (± 1 year) as a participant with low back pain.

Exclusion Criteria:

* Diagnosis of back conditions other than chronic primary LBP e.g., failed back surgery syndrome, spondylosis, spondylolisthesis, spinal stenosis, herniated disc, infection, etc.;
* Presence of pain in another body location that is more severe than the pain in the lower back;
* Presence of a neurological deficit i.e., sensation loss, muscle weakness, decreased deep tendon reflexes;
* Presence of contraindications to spinal manipulative therapy e.g., recent fracture, history of spinal surgery, cauda equina syndrome, inflammatory arthritis, taking anticoagulant medication, active cancer, moderate to severe osteoporosis, abdominal aortic aneurysm;
* Underwent surgery in the last 3 months;
* Pregnancy, ≤ 3 months post-partum or planning to get pregnant in the next 12 months;
* History of spinal manipulative therapy in the past 12 months;
* Scoliosis ≥ 20°;
* BMI ≥ 40;
* Insufficient language skills in French to complete the questionnaires;
* Open or pending litigation for LBP or seeking/receiving disability compensation;
* Diagnosis of an illness affecting the sensorimotor functions e.g., diabetes, multiple sclerosis, amyotrophic lateral sclerosis;
* Diagnosis of mental health disorders (with the exception of anxiety and depression);
* Current drug or alcohol dependence;
* Skin of type I on the Fitzpatrick scale;
* (For healthy volunteers only) Regular use of pain medication or usage in the 48 h prior to data collection;
* (For healthy volunteers only) History of chronic pain;
* (For healthy volunteers only) Acute pain on the days of data collection.

Primary outcomes:
measure: low back pain intensity
timeFrame: baseline, 1- , 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 26-, 39-, 52- and 64-weeks post-randomization.
measure: temporal summation of second pain
timeFrame: baseline, 4- and 12-weeks post-randomization.
Secondary outcomes:
measure: low back pain frequency and duration
timeFrame: baseline, 1- , 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 26-, 39-, 52- and 64-weeks post-randomization.
measure: Pressure pain thresholds (PPTs)
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: C-fiber-related brain responses
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Oswestry Disability Index (ODI)
timeFrame: baseline, 4-, 12-, 26-, 39-, 52- and 64-weeks post-randomization.
measure: Back performance scale (BPS)
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Five times sit-to-stand test
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Depression
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Anxiety
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Pain catastrophizing
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Kinesiophobia
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Pain vigilance
timeFrame: baseline, 4- and 12-weeks post-randomization.
measure: Patient's global impression of change
timeFrame: After the last treatment session (12-weeks post-randomization)
measure: Expectations of pain relief
timeFrame: baseline and 4-weeks post-randomization.
measure: Contextual factors (healing encounters and attitudes lists (HEAL))
timeFrame: baseline, 4- and 12-weeks post-randomization.
Other outcomes:
measure: Adverse events (AE)
timeFrame: 1- , 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13-weeks post-randomization.
measure: Blinding
timeFrame: After the last treatment session (12-weeks post-randomization)
measure: Number of other treatments for low back pain
timeFrame: 1- , 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-weeks post-randomization.
Locations:
city: Trois-Rivières
country: Canada
facility: Université du Québec à Trois-Rivières
state: Quebec
Study officials:
affiliation: Université du Québec à Trois-Rivières
name: Mathieu Piché
role: PRINCIPAL_INVESTIGATOR
References:
citation: Buchbinder R, Underwood M, Hartvigsen J, Maher CG. The Lancet Series call to action to reduce low value care for low back pain: an update. Pain. 2020 Sep;161 Suppl 1(1):S57-S64. doi: 10.1097/j.pain.0000000000001869. No abstract available.
citation: Cormier S, Lavigne GL, Choiniere M, Rainville P. Expectations predict chronic pain treatment outcomes. Pain. 2016 Feb;157(2):329-338. doi: 10.1097/j.pain.0000000000000379.
citation: Corp N, Mansell G, Stynes S, Wynne-Jones G, Morso L, Hill JC, van der Windt DA. Evidence-based treatment recommendations for neck and low back pain across Europe: A systematic review of guidelines. Eur J Pain. 2021 Feb;25(2):275-295. doi: 10.1002/ejp.1679. Epub 2020 Nov 12.
citation: Dieleman JL, Cao J, Chapin A, Chen C, Li Z, Liu A, Horst C, Kaldjian A, Matyasz T, Scott KW, Bui AL, Campbell M, Duber HC, Dunn AC, Flaxman AD, Fitzmaurice C, Naghavi M, Sadat N, Shieh P, Squires E, Yeung K, Murray CJL. US Health Care Spending by Payer and Health Condition, 1996-2016. JAMA. 2020 Mar 3;323(9):863-884. doi: 10.1001/jama.2020.0734.
citation: Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J; IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005 Jan;113(1-2):9-19. doi: 10.1016/j.pain.2004.09.012. No abstract available.
citation: Fitzcharles MA, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Hauser W. Chronic primary musculoskeletal pain: a new concept of nonstructural regional pain. Pain Rep. 2022 Aug 9;7(5):e1024. doi: 10.1097/PR9.0000000000001024. eCollection 2022 Sep-Oct.
citation: Funabashi M, Gorrell LM, Pohlman KA, Bergna A, Heneghan NR. Definition and classification for adverse events following spinal and peripheral joint manipulation and mobilization: A scoping review. PLoS One. 2022 Jul 15;17(7):e0270671. doi: 10.1371/journal.pone.0270671. eCollection 2022.
citation: George SZ, Fritz JM, Silfies SP, Schneider MJ, Beneciuk JM, Lentz TA, Gilliam JR, Hendren S, Norman KS. Interventions for the Management of Acute and Chronic Low Back Pain: Revision 2021. J Orthop Sports Phys Ther. 2021 Nov;51(11):CPG1-CPG60. doi: 10.2519/jospt.2021.0304.
citation: Gevers-Montoro C, Provencher B, Descarreaux M, Ortega de Mues A, Piche M. Neurophysiological mechanisms of chiropractic spinal manipulation for spine pain. Eur J Pain. 2021 Aug;25(7):1429-1448. doi: 10.1002/ejp.1773. Epub 2021 Apr 15.
citation: Gevers-Montoro C, Provencher B, Northon S, Stedile-Lovatel JP, Ortega de Mues A, Piche M. Chiropractic Spinal Manipulation Prevents Secondary Hyperalgesia Induced by Topical Capsaicin in Healthy Individuals. Front Pain Res (Lausanne). 2021 Jul 20;2:702429. doi: 10.3389/fpain.2021.702429. eCollection 2021.
citation: Graven-Nielsen T. Mechanisms and manifestations in musculoskeletal pain: from experimental to clinical pain settings. Pain. 2022 Nov 1;163(Suppl 1):S29-S45. doi: 10.1097/j.pain.0000000000002690. Epub 2022 May 15. No abstract available.
citation: Greco CM, Yu L, Johnston KL, Dodds NE, Morone NE, Glick RM, Schneider MJ, Klem ML, McFarland CE, Lawrence S, Colditz J, Maihoefer CC, Jonas WB, Ryan ND, Pilkonis PA. Measuring nonspecific factors in treatment: item banks that assess the healthcare experience and attitudes from the patient's perspective. Qual Life Res. 2016 Jul;25(7):1625-34. doi: 10.1007/s11136-015-1178-1. Epub 2015 Nov 12.
citation: Haas M, Vavrek D, Peterson D, Polissar N, Neradilek MB. Dose-response and efficacy of spinal manipulation for care of chronic low back pain: a randomized controlled trial. Spine J. 2014 Jul 1;14(7):1106-16. doi: 10.1016/j.spinee.2013.07.468. Epub 2013 Oct 16.
citation: Hartvigsen J, Hancock MJ, Kongsted A, Louw Q, Ferreira ML, Genevay S, Hoy D, Karppinen J, Pransky G, Sieper J, Smeets RJ, Underwood M; Lancet Low Back Pain Series Working Group. What low back pain is and why we need to pay attention. Lancet. 2018 Jun 9;391(10137):2356-2367. doi: 10.1016/S0140-6736(18)30480-X. Epub 2018 Mar 21.
citation: Hohenschurz-Schmidt D, Vase L, Scott W, Annoni M, Ajayi OK, Barth J, Bennell K, Berna C, Bialosky J, Braithwaite F, Finnerup NB, Williams ACC, Carlino E, Cerritelli F, Chaibi A, Cherkin D, Colloca L, Cote P, Darnall BD, Evans R, Fabre L, Faria V, French S, Gerger H, Hauser W, Hinman RS, Ho D, Janssens T, Jensen K, Johnston C, Juhl Lunde S, Keefe F, Kerns RD, Koechlin H, Kongsted A, Michener LA, Moerman DE, Musial F, Newell D, Nicholas M, Palermo TM, Palermo S, Peerdeman KJ, Pogatzki-Zahn EM, Puhl AA, Roberts L, Rossettini G, Tomczak Matthiesen S, Underwood M, Vaucher P, Vollert J, Wartolowska K, Weimer K, Werner CP, Rice ASC, Draper-Rodi J. Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies: the CoPPS Statement. BMJ. 2023 May 25;381:e072108. doi: 10.1136/bmj-2022-072108. No abstract available.
citation: Hurwitz EL, Randhawa K, Yu H, Cote P, Haldeman S. The Global Spine Care Initiative: a summary of the global burden of low back and neck pain studies. Eur Spine J. 2018 Sep;27(Suppl 6):796-801. doi: 10.1007/s00586-017-5432-9. Epub 2018 Feb 26.
citation: Korownyk CS, Montgomery L, Young J, Moore S, Singer AG, MacDougall P, Darling S, Ellis K, Myers J, Rochford C, Taillefer MC, Allan GM, Perry D, Moe SS, Ton J, Kolber MR, Kirkwood J, Thomas B, Garrison S, McCormack JP, Falk J, Dugre N, Sept L, Turgeon RD, Paige A, Potter J, Nickonchuk T, Train AD, Weresch J, Chan K, Lindblad AJ. PEER simplified chronic pain guideline: Management of chronic low back, osteoarthritic, and neuropathic pain in primary care. Can Fam Physician. 2022 Mar;68(3):179-190. doi: 10.46747/cfp.6803179.
citation: Kosek E, Clauw D, Nijs J, Baron R, Gilron I, Harris RE, Mico JA, Rice ASC, Sterling M. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. Pain. 2021 Nov 1;162(11):2629-2634. doi: 10.1097/j.pain.0000000000002324. No abstract available.
citation: Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009 Sep;10(9):895-926. doi: 10.1016/j.jpain.2009.06.012.
citation: McPhee ME, Vaegter HB, Graven-Nielsen T. Alterations in pronociceptive and antinociceptive mechanisms in patients with low back pain: a systematic review with meta-analysis. Pain. 2020 Mar;161(3):464-475. doi: 10.1097/j.pain.0000000000001737.
citation: Mucke M, Cuhls H, Radbruch L, Baron R, Maier C, Tolle T, Treede RD, Rolke R. Quantitative sensory testing (QST). English version. Schmerz. 2021 Nov;35(Suppl 3):153-160. doi: 10.1007/s00482-015-0093-2.
citation: Nicholas M, Vlaeyen JWS, Rief W, Barke A, Aziz Q, Benoliel R, Cohen M, Evers S, Giamberardino MA, Goebel A, Korwisi B, Perrot S, Svensson P, Wang SJ, Treede RD; IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain. 2019 Jan;160(1):28-37. doi: 10.1097/j.pain.0000000000001390.
citation: Nijs J, Apeldoorn A, Hallegraeff H, Clark J, Smeets R, Malfliet A, Girbes EL, De Kooning M, Ickmans K. Low back pain: guidelines for the clinical classification of predominant neuropathic, nociceptive, or central sensitization pain. Pain Physician. 2015 May-Jun;18(3):E333-46.
citation: Nim CG, Kawchuk GN, Schiottz-Christensen B, O'Neill S. The effect on clinical outcomes when targeting spinal manipulation at stiffness or pain sensitivity: a randomized trial. Sci Rep. 2020 Sep 3;10(1):14615. doi: 10.1038/s41598-020-71557-y.
citation: Ozudogru A, Canli M, Ceylan I, Kuzu S, Alkan H, Karacay BC. Five Times Sit-to-Stand Test in people with non-specific chronic low back pain-a cross-sectional test-retest reliability study. Ir J Med Sci. 2023 Aug;192(4):1903-1908. doi: 10.1007/s11845-022-03223-3. Epub 2022 Nov 15.
citation: Plaghki L, Mouraux A. How do we selectively activate skin nociceptors with a high power infrared laser? Physiology and biophysics of laser stimulation. Neurophysiol Clin. 2003 Dec;33(6):269-77. doi: 10.1016/j.neucli.2003.10.003.
citation: Plaghki L, Mouraux A. EEG and laser stimulation as tools for pain research. Curr Opin Investig Drugs. 2005 Jan;6(1):58-64.
citation: Provencher B, Northon S, Gevers Montoro C, O'Shaughnessy J, Piche M. Effects of chiropractic spinal manipulation on laser-evoked pain and brain activity. J Physiol Sci. 2021 Jun 24;71(1):20. doi: 10.1186/s12576-021-00804-2.
citation: Provencher B, Northon S, Piche M. Segmental Chiropractic Spinal Manipulation Does not Reduce Pain Amplification and the Associated Pain-Related Brain Activity in a Capsaicin-Heat Pain Model. Front Pain Res (Lausanne). 2021 Nov 1;2:733727. doi: 10.3389/fpain.2021.733727. eCollection 2021.
citation: Puhl AA, Reinhart CJ, Doan JB, Vernon H. The quality of placebos used in randomized, controlled trials of lumbar and pelvic joint thrust manipulation-a systematic review. Spine J. 2017 Mar;17(3):445-456. doi: 10.1016/j.spinee.2016.11.003. Epub 2016 Nov 22.
citation: Schaffler K, Nicolas LB, Borta A, Brand T, Reitmeir P, Roebling R, Scholpp J. Investigation of the predictive validity of laser-EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers. Br J Clin Pharmacol. 2017 Jul;83(7):1424-1435. doi: 10.1111/bcp.13247. Epub 2017 Feb 27.
citation: Shraim MA, Masse-Alarie H, Hall LM, Hodges PW. Systematic Review and Synthesis of Mechanism-based Classification Systems for Pain Experienced in the Musculoskeletal System. Clin J Pain. 2020 Oct;36(10):793-812. doi: 10.1097/AJP.0000000000000860.
citation: Starkweather AR, Heineman A, Storey S, Rubia G, Lyon DE, Greenspan J, Dorsey SG. Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain. Appl Nurs Res. 2016 Feb;29:237-41. doi: 10.1016/j.apnr.2015.03.013. Epub 2015 Apr 8.
citation: Stevans JM, Delitto A, Khoja SS, Patterson CG, Smith CN, Schneider MJ, Freburger JK, Greco CM, Freel JA, Sowa GA, Wasan AD, Brennan GP, Hunter SJ, Minick KI, Wegener ST, Ephraim PL, Friedman M, Beneciuk JM, George SZ, Saper RB. Risk Factors Associated With Transition From Acute to Chronic Low Back Pain in US Patients Seeking Primary Care. JAMA Netw Open. 2021 Feb 1;4(2):e2037371. doi: 10.1001/jamanetworkopen.2020.37371.
citation: Strand LI, Moe-Nilssen R, Ljunggren AE. Back Performance Scale for the assessment of mobility-related activities in people with back pain. Phys Ther. 2002 Dec;82(12):1213-23.
citation: Verdugo RJ, Matamala JM, Inui K, Kakigi R, Valls-Sole J, Hansson P, Nilsen KB, Lombardi R, Lauria G, Petropoulos IN, Malik RA, Treede RD, Baumgartner U, Jara PA, Campero M. Review of techniques useful for the assessment of sensory small fiber neuropathies: Report from an IFCN expert group. Clin Neurophysiol. 2022 Apr;136:13-38. doi: 10.1016/j.clinph.2022.01.002. Epub 2022 Jan 19.
citation: Vlaeyen JWS, Crombez G, Linton SJ. The fear-avoidance model of pain. Pain. 2016 Aug;157(8):1588-1589. doi: 10.1097/j.pain.0000000000000574. No abstract available.
citation: Wheeler CHB, Williams ACC, Morley SJ. Meta-analysis of the psychometric properties of the Pain Catastrophizing Scale and associations with participant characteristics. Pain. 2019 Sep;160(9):1946-1953. doi: 10.1097/j.pain.0000000000001494.
citation: Wang YP, Gorenstein C. Psychometric properties of the Beck Depression Inventory-II: a comprehensive review. Braz J Psychiatry. 2013 Oct-Dec;35(4):416-31. doi: 10.1590/1516-4446-2012-1048. Epub 2013 Dec 23.
citation: Denis I, Fortin L. Development of a French-Canadian version of the Oswestry Disability Index: cross-cultural adaptation and validation. Spine (Phila Pa 1976). 2012 Apr 1;37(7):E439-44. doi: 10.1097/BRS.0b013e318233eaf9.
citation: Poquet N, Lin C. The Brief Pain Inventory (BPI). J Physiother. 2016 Jan;62(1):52. doi: 10.1016/j.jphys.2015.07.001. Epub 2015 Aug 21. No abstract available.