Effectiveness and brain mechanism of rTMS combined with quadriceps strength training in individuals with knee osteoarthritis: Study protocol for a randomized controlled trial

Abstract

Abstract Background: Quadriceps training is necessary in function, activity of daily living and quality of life for patients with knee osteoarthritis (KOA) but it did not reduce the rate of surgical treatment (replacement of knee) for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial magnetic stimulation (TMS), as a non-invasive brain stimulation technique, which uses magnetic pulse on the central nervous system, stimulates the excitability of nerve cells, enhances the functional connectivity of brain regions and improves maladaptive plasticity. However，the therapeutic effect of two rehabilitation techniques combination in patients with KOA remains unclear. Therefore, the purpose of this study is to investigate whether the high-frequency rTMS combined with quadriceps strength training can improve the function in KOA more effectively than quadriceps training alone and explore the brain mechanism of this combined rehabilitation. Methods: This study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks intervention and 6 months follow-up. One hundred and twelve participants with KOA will be received usual care management and randomized into four subgroups including quadriceps strength training (QT); high-frequency rTMS training (HT); sham rTMS and quadriceps strength training (ST+Q); high-frequency rTMS and quadriceps strength training (HT+Q). The rehabilitation interventions in four groups will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during intervention and 1 months, 3 months and 6 months during follow-up period. The primary outcomes are visual analog scale (VAS) and isokinetic muscle strength test. Secondary outcomes are include Knee Injury and Osteoarthritis Outcome Score (KOOS)，36-Item Short-Form Health Survey (SF-36), rTMS and magnetic resonance imaging (MRI). Discussion: The study will provide evidence for the effects and brain mechanism of high frequency rTMS on improving function in KOA patients. High frequency rTMS can be added into the muscle training program for KOA patients as a supplementary therapy content if it is proved to be effective. Trial registration: Chinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.