Clinical trial NCT06228573: Transcranial Direct Current Stimulation and Yoga for Knee Osteoarthritis
Official title: Combining Transcranial Direct Current Stimulation and Yoga for Improved Pain Management for Knee Osteoarthritis: A Pilot and Feasibility Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Knee Osteoarthritis
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: The Arthritis Society, Canada
First posted: 2024-01-29
Enrollment: 68
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: People with knee arthritis often experience constant pain, and current treatments aren't very effective. This can lead to limited movement and more health problems. Knee arthritis is a big part of healthcare costs in Canada, and its pain is a major reason people see doctors. The pain is linked to complex nervous system changes, making current treatments, like exercise, not very successful.

To address this, researchers suggest a new approach combining two things: a brain stimulation technique called Transcranial Direct Current Stimulation (tDCS) and yoga. TDCS helps with pain by changing how the brain works, and yoga, a safe practice, focuses on overall well-being. Together, the investigators aim to improve how the nervous system works from top to bottom.

The research project wants to change how the arthritis pain is being managed by focusing on how it works. The investigators plan to test this combo in a study comparing real tDCS plus yoga with fake tDCS plus yoga. The investigators will look not only at pain but also at other measures related to pain and how the nervous system works. This new mix could be a meaningful way to reduce pain for people with knee arthritis.

Detailed description: Background:

'Omnipresent' is a common word that people living with knee osteoarthritis (KOA) use to describe the associated pain, with its unpredictability causing physical, social and emotional disruption. For many, KOA pain leads to limited mobility, reduced quality of life and increased healthcare costs KOA pain and its mechanisms are known to be complex, with alterations in nervous system signaling (ANSS) leading to persistent pain, and treatment failure to guideline-based care. Unfortunately, there is a lack of effective conservative treatments for KOA pain, including exercise which elicits only modest analgesic effects and has little impact on ANSS. To improve conservative pain management for people with KOA, it is imperative to design mechanism informed interventions and explore bold new ways to modulate ANSS to optimize patient outcomes.

The investigators' novel intervention is focused on addressing the biomarker of ANSS. The investigators' solution involves using non-invasive brain stimulation (NIBS) in the form of transcranial direct current stimulation (tDCS), paired with the mind-body practice of yoga, to modify neural pathways. This is a promising and safe alternative to medications - which risk habituation, adverse events, and addiction - and that builds on the limited efficacy of performing/examining exercise in isolation. To the investigators' knowledge, this is the first trial to use this combination for chronic pain and in people with KOA. The investigators have chosen this combination as tDCS has the potential to produce synergistic nervous system effects with yoga and bolster impacts on pain.

tDCS alleviates pain in older adults with KOA, particularly when combined with strengthening exercise or mindfulness. tDCS has demonstrated improved efficiency of conditioned pain modulation (CPM) resulting in pain reduction in older adults with KOA displaying deficient CPM. Meta-analyses of tDCS for the treatment of chronic pain report small to moderate effects on pain reduction, while a meta-analysis of NIBS (including tDCS) plus exercise showed moderate to large effect sizes (-0.62) compared to sham NIBS plus exercise.

The investigators' approach combining 13 sessions of tDCS with yoga provides the benefits of strengthening and mindfulness in addition to nervous system regulation with the potential to produce large effects for pain reduction.

Yoga modulates brain networks and is safe and accessible for many with KOA Importantly, yoga is safe for people with comorbidities through its combination of physical postures, breathing exercises, meditation and relaxation that are hypothesized to reduce pain by regulating top down and bottom-up input into the physiological systems modulating nociceptive signals. Evidence from fMRI studies indicates that yoga modifies functional connectivity in networks involved in chronic pain. Yoga is conditionally recommended by KOA guidelines due to low quality evidence and few studies.

The current project seeks to shift the current paradigm for conservative pain management for people with KOA by assessing a pain mechanism informed treatment strategy in a multi-center pilot and feasibility randomized controlled trial. The investigators hypothesize that real tDCS and yoga will provide clinically meaningful reductions in pain compared to sham tDCS and yoga.

This is a feasibility and pilot double-blind, randomized sham-controlled multi-center, two-arm clinical trial with a 1:1 allocation ratio. Participants will be randomized to receive active or sham tDCS and yoga for 9 weeks. Follow-up will occur at the end of the intervention and at 3 months. The Conceptual Framework for Defining Feasibility and Pilot studies, and the Standard Protocol Items- Recommendations for Intervention Trials will be used. Study results will be reported using the extended CONSORT guideline for pilot trials and the Check List Standardizing the Reporting of Interventions For Yoga (CLARIFY).

Eligibility criteria: Inclusion Criteria:

* community dwelling adults from Sherbrooke, Quebec, Hamilton and London, Ontario fulfilling the NICE criteria for KOA
* ≥45 years of age
* Diagnosis of Knee osteoarthritis OR
* Having movement-related joint pain with either no morning knee stiffness or stiffness of 30 minutes or less AND
* Experiencing an average pain intensity of ≥3 /10 in the past month

Exclusion Criteria:

* Systemic inflammatory arthritis.
* Any knee injection in the past 3 months.
* Inability to independently get up and down from the floor.
* Lower limb trauma or surgery within the last 6 months.
* Current participation in another OA clinical trial.
* Use of mobility aids.
* Currently receiving care for KOA pain (e.g., physiotherapy).
* Planned absences exceeding 1 week.
* Contraindications to transcranial direct current stimulation (tDCS) such as neurological or neuropsychiatric conditions.
* History of brain surgery or tumor.
* Metallic implants.
* Epilepsy or history of substance abuse or dependence.
* Cochlear or ocular implant.
* Presence of a pacemaker or cardiac defibrillator.
* Eczema on the scalp.

Primary outcomes:
measure: Percentage of complete follow up
timeFrame: 9 weeks and 3 months
Secondary outcomes:
measure: Brief Pain Inventory - Numeric Rating Scale
timeFrame: 9 weeks and 3 months
measure: Modified Charlson Comorbidity Index (CCI)
timeFrame: 9 weeks and 3 months
measure: Endogenous pain modulation
timeFrame: 9 weeks
measure: Pain interference
timeFrame: 9 weeks and 3 months
measure: Pain catastrophizing
timeFrame: 9 weeks and 3 months
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 9 weeks and 3 months
measure: Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 9 weeks and 3 months
measure: Multi-joint pain; Body diagram
timeFrame: 9 weeks and 3 months
measure: Knee Awareness
timeFrame: 9 weeks and 3 months
measure: Functional leg strength
timeFrame: 9 weeks
measure: Medication use
timeFrame: 9 weeks and 3 months
measure: Adverse events
timeFrame: 9 weeks
measure: Patient global impression of change
timeFrame: 9 weeks and 3 months
measure: Blinding effectiveness
timeFrame: 3 months
measure: Usefulness of the program for managing knee OA measured on a 5 point Likert scale
timeFrame: 9 weeks
measure: Frequency of the program measured on a 5 point Likert scale
timeFrame: 9 weeks
measure: Duration of the program on a 5 point Likert scale
timeFrame: 9 weeks
measure: Acceptability of the delivery of the brain stimulation on a 5 point Likert scale
timeFrame: 9 weeks
measure: Acceptability of the delivery of the yoga session of the program on a 5 point Likert scale
timeFrame: 9 weeks
measure: How likely are you to recommend the program you attended for others with knee OA?
timeFrame: 9 weeks
measure: How burdensome did you find completing the questionnaires?
timeFrame: 3 months
measure: How burdensome did you find completing the physical assessments?
timeFrame: 9 weeks
measure: rate of adherence measured by percentage of sessions attended and home sessions completed
timeFrame: 9 weeks
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: University of Western Ontario
state: Ontario
city: Sherbrooke
country: Canada
facility: Université de Sherbrooke
state: Quebec
Study officials:
affiliation: McMaster University
name: Lisa Carlesso, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wallis JA, Taylor NF, Bunzli S, Shields N. Experience of living with knee osteoarthritis: a systematic review of qualitative studies. BMJ Open. 2019 Sep 24;9(9):e030060. doi: 10.1136/bmjopen-2019-030060.
citation: Calders P, Van Ginckel A. Presence of comorbidities and prognosis of clinical symptoms in knee and/or hip osteoarthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. 2018 Jun;47(6):805-813. doi: 10.1016/j.semarthrit.2017.10.016. Epub 2017 Oct 31.
citation: Kendzerska T, Juni P, King LK, Croxford R, Stanaitis I, Hawker GA. The longitudinal relationship between hand, hip and knee osteoarthritis and cardiovascular events: a population-based cohort study. Osteoarthritis Cartilage. 2017 Nov;25(11):1771-1780. doi: 10.1016/j.joca.2017.07.024. Epub 2017 Aug 9.
citation: Arthritis Alliance of Canada. The Impact of Arthritis in Canada: Today and over the Next 30 years. Executive Summary. 2011.
citation: Sharif B, Kopec JA, Wong H, Anis AH. Distribution and Drivers of Average Direct Cost of Osteoarthritis in Canada From 2003 to 2010. Arthritis Care Res (Hoboken). 2017 Feb;69(2):243-251. doi: 10.1002/acr.22933.
citation: Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage. 2013 Sep;21(9):1145-53. doi: 10.1016/j.joca.2013.03.018.
citation: Fingleton C, Smart K, Moloney N, Fullen BM, Doody C. Pain sensitization in people with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2015 Jul;23(7):1043-56. doi: 10.1016/j.joca.2015.02.163. Epub 2015 Mar 5.
citation: Carlesso LC, Segal NA, Frey-Law L, Zhang Y, Na L, Nevitt M, Lewis CE, Neogi T. Pain Susceptibility Phenotypes in Those Free of Knee Pain With or at Risk of Knee Osteoarthritis: The Multicenter Osteoarthritis Study. Arthritis Rheumatol. 2019 Apr;71(4):542-549. doi: 10.1002/art.40752. Epub 2019 Feb 7.
citation: O'Leary H, Smart KM, Moloney NA, Blake C, Doody CM. Pain sensitization associated with nonresponse after physiotherapy in people with knee osteoarthritis. Pain. 2018 Sep;159(9):1877-1886. doi: 10.1097/j.pain.0000000000001288.
citation: Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019 Nov;27(11):1578-1589. doi: 10.1016/j.joca.2019.06.011. Epub 2019 Jul 3.
citation: Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, Callahan L, Copenhaver C, Dodge C, Felson D, Gellar K, Harvey WF, Hawker G, Herzig E, Kwoh CK, Nelson AE, Samuels J, Scanzello C, White D, Wise B, Altman RD, DiRenzo D, Fontanarosa J, Giradi G, Ishimori M, Misra D, Shah AA, Shmagel AK, Thoma LM, Turgunbaev M, Turner AS, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020 Feb;72(2):220-233. doi: 10.1002/art.41142. Epub 2020 Jan 6.
citation: Fernandes L, Hagen KB, Bijlsma JW, Andreassen O, Christensen P, Conaghan PG, Doherty M, Geenen R, Hammond A, Kjeken I, Lohmander LS, Lund H, Mallen CD, Nava T, Oliver S, Pavelka K, Pitsillidou I, da Silva JA, de la Torre J, Zanoli G, Vliet Vlieland TP; European League Against Rheumatism (EULAR). EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis. 2013 Jul;72(7):1125-35. doi: 10.1136/annrheumdis-2012-202745. Epub 2013 Apr 17.
citation: Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee: a Cochrane systematic review. Br J Sports Med. 2015 Dec;49(24):1554-7. doi: 10.1136/bjsports-2015-095424. Epub 2015 Sep 24.
citation: Hall M, Dobson F, Plinsinga M, Mailloux C, Starkey S, Smits E, Hodges P, Vicenzino B, Schabrun SM, Masse-Alarie H. Effect of exercise on pain processing and motor output in people with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2020 Dec;28(12):1501-1513. doi: 10.1016/j.joca.2020.07.009. Epub 2020 Aug 9.
citation: Ahn H, Sorkpor S, Miao H, Zhong C, Jorge R, Park L, Abdi S, Cho RY. Home-based self-administered transcranial direct current stimulation in older adults with knee osteoarthritis pain: An open-label study. J Clin Neurosci. 2019 Aug;66:61-65. doi: 10.1016/j.jocn.2019.05.023. Epub 2019 May 29.
citation: Ahn H, Suchting R, Woods AJ, Miao H, Green C, Cho RY, Choi E, Fillingim RB. Bayesian analysis of the effect of transcranial direct current stimulation on experimental pain sensitivity in older adults with knee osteoarthritis: randomized sham-controlled pilot clinical study. J Pain Res. 2018 Sep 27;11:2071-2082. doi: 10.2147/JPR.S173080. eCollection 2018.
citation: Tavares DRB, Okazaki JEF, Santana MVA, Pinto ACPN, Tutiya KK, Gazoni FM, Pinto CB, Santos FC, Fregni F, Trevisani VFM. Motor cortex transcranial direct current stimulation effects on knee osteoarthritis pain in elderly subjects with dysfunctional descending pain inhibitory system: A randomized controlled trial. Brain Stimul. 2021 May-Jun;14(3):477-487. doi: 10.1016/j.brs.2021.02.018. Epub 2021 Mar 5.
citation: Pinto CB, Teixeira Costa B, Duarte D, Fregni F. Transcranial Direct Current Stimulation as a Therapeutic Tool for Chronic Pain. J ECT. 2018 Sep;34(3):e36-e50. doi: 10.1097/YCT.0000000000000518.
citation: Lee PG, Jackson EA, Richardson CR. Exercise Prescriptions in Older Adults. Am Fam Physician. 2017 Apr 1;95(7):425-432.
citation: Solomon DH, Schneeweiss S, Glynn RJ, Kiyota Y, Levin R, Mogun H, Avorn J. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation. 2004 May 4;109(17):2068-73. doi: 10.1161/01.CIR.0000127578.21885.3E. Epub 2004 Apr 19.
citation: Pearson N, Prosko S, Sullivan M, Taylor MJ. White Paper: Yoga Therapy and Pain-How Yoga Therapy Serves in Comprehensive Integrative Pain Management, and How It Can Do More. Int J Yoga Therap. 2020 Jan 1;30(1):117-133. doi: 10.17761/2020-D-19-00074.
citation: MacKay C, Jaglal SB, Sale J, Badley EM, Davis AM. A qualitative study of the consequences of knee symptoms: 'It's like you're an athlete and you go to a couch potato'. BMJ Open. 2014 Oct 16;4(10):e006006. doi: 10.1136/bmjopen-2014-006006.
citation: Nyvang J, Hedstrom M, Gleissman SA. It's not just a knee, but a whole life: A qualitative descriptive study on patients' experiences of living with knee osteoarthritis and their expectations for knee arthroplasty. Int J Qual Stud Health Well-being. 2016 Mar 31;11:30193. doi: 10.3402/qhw.v11.30193. eCollection 2016.
citation: Chang WJ, Bennell KL, Hodges PW, Hinman RS, Young CL, Buscemi V, Liston MB, Schabrun SM. Addition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial. PLoS One. 2017 Jun 30;12(6):e0180328. doi: 10.1371/journal.pone.0180328. eCollection 2017.
citation: Ahn H, Zhong C, Miao H, Chaoul A, Park L, Yen IH, Vila MA, Sorkpor S, Abdi S. Efficacy of combining home-based transcranial direct current stimulation with mindfulness-based meditation for pain in older adults with knee osteoarthritis: A randomized controlled pilot study. J Clin Neurosci. 2019 Dec;70:140-145. doi: 10.1016/j.jocn.2019.08.047. Epub 2019 Aug 14.
citation: Cardenas-Rojas A, Pacheco-Barrios K, Giannoni-Luza S, Rivera-Torrejon O, Fregni F. Noninvasive brain stimulation combined with exercise in chronic pain: a systematic review and meta-analysis. Expert Rev Neurother. 2020 Apr;20(4):401-412. doi: 10.1080/14737175.2020.1738927. Epub 2020 Mar 14.
citation: Sefat O, Salehinejad MA, Danilewitz M, Shalbaf R, Vila-Rodriguez F. Combined Yoga and Transcranial Direct Current Stimulation Increase Functional Connectivity and Synchronization in the Frontal Areas. Brain Topogr. 2022 Mar;35(2):207-218. doi: 10.1007/s10548-022-00887-z. Epub 2022 Jan 29.
citation: Lauche R, Hunter DJ, Adams J, Cramer H. Yoga for Osteoarthritis: a Systematic Review and Meta-analysis. Curr Rheumatol Rep. 2019 Jul 23;21(9):47. doi: 10.1007/s11926-019-0846-5.
citation: Eldridge SM, Lancaster GA, Campbell MJ, Thabane L, Hopewell S, Coleman CL, Bond CM. Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework. PLoS One. 2016 Mar 15;11(3):e0150205. doi: 10.1371/journal.pone.0150205. eCollection 2016.
citation: Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, Dore CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3-201302050-00583.
citation: Moonaz S, Nault D, Cramer H, Ward L. CLARIFY 2021: explanation and elaboration of the Delphi-based guidelines for the reporting of yoga research. BMJ Open. 2021 Aug 5;11(8):e045812. doi: 10.1136/bmjopen-2020-045812.
citation: Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, Robson R, Thabane M, Giangregorio L, Goldsmith CH. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010 Jan 6;10:1. doi: 10.1186/1471-2288-10-1.
citation: Roizenblatt S, Fregni F, Gimenez R, Wetzel T, Rigonatti SP, Tufik S, Boggio PS, Valle AC. Site-specific effects of transcranial direct current stimulation on sleep and pain in fibromyalgia: a randomized, sham-controlled study. Pain Pract. 2007 Dec;7(4):297-306. doi: 10.1111/j.1533-2500.2007.00152.x. Epub 2007 Nov 6.
citation: Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006 May;122(1-2):197-209. doi: 10.1016/j.pain.2006.02.023. Epub 2006 Mar 27.
citation: Kim YJ, Ku J, Kim HJ, Im DJ, Lee HS, Han KA, Kang YJ. Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy. Ann Rehabil Med. 2013 Dec;37(6):766-76. doi: 10.5535/arm.2013.37.6.766. Epub 2013 Dec 23.
citation: Mori F, Codeca C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, Bernardi G, Koch G, Centonze D. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain. 2010 May;11(5):436-42. doi: 10.1016/j.jpain.2009.08.011. Epub 2009 Dec 16.
citation: Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
citation: Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006 Apr;117(4):845-50. doi: 10.1016/j.clinph.2005.12.003. Epub 2006 Jan 19.
citation: Kessler SK, Turkeltaub PE, Benson JG, Hamilton RH. Differences in the experience of active and sham transcranial direct current stimulation. Brain Stimul. 2012 Apr;5(2):155-62. doi: 10.1016/j.brs.2011.02.007. Epub 2011 Mar 27.
citation: Palm U, Reisinger E, Keeser D, Kuo MF, Pogarell O, Leicht G, Mulert C, Nitsche MA, Padberg F. Evaluation of sham transcranial direct current stimulation for randomized, placebo-controlled clinical trials. Brain Stimul. 2013 Jul;6(4):690-5. doi: 10.1016/j.brs.2013.01.005. Epub 2013 Feb 8.