Immediate Effects of rTMS on Excitability of the Quadriceps With Knee Osteoarthritis

Study Overview
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Brief Summary
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The purpose of the study is to identify things that influence the ability to turn on the thigh muscle (quadriceps). The thigh muscle tends to be under active with knee osteoarthritis, which may make it difficult to strengthen the muscle. The investigators are also testing a new technology called repetitive transcranial magnetic stimulation (rTMS) to determine whether it may help turn up activity in the under active thigh muscle immediately after its application. rTMS uses a targeted pulsed magnetic field, similar to what is used in an MRI (magnetic resonance imaging) machine to send an electrical signal from the brain to the thigh muscle.

Detailed Description
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The investigators will recruit up to 20 people with symptomatic knee osteoarthritis. The 20 eligible participants will attend 3 sessions in the laboratory. Session 1 is to collect data for Aim 1. Sessions 2 and 3 will include the rTMS interventions and data collection for Aim 2. Aim 1 is a descriptive study to compare the neural (cortical and corticospinal) excitability of the quadriceps in the symptomatic knee to the asymptomatic knee in participants with knee osteoarthritis. The investigators will examine the associations between neural excitability and clinical measures of pain, strength, function, and coping styles. Aim 2 is a double blind, crossover study design. Each participant will partake in two testing sessions, spaced 1 week apart. The investigators will evaluate outcome measures prior to and following the true intervention versus the sham intervention. The true intervention is rTMS + exercise. The sham is sham rTMS + exercise. The primary outcome measures are quadriceps strength, as measured from a maximal isometric voluntary contraction, and quadriceps central activation ratio (CAR), as calculated from the torque values from the voluntary strength measurement and a brief, intense electrical stimulus. Secondary measures evaluate effects of the intervention on 1) clinical measures of pain and functional performance, 2) corticospinal excitability, and 3) intracortical inhibition and facilitation.

Official Title
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Immediate Effects of rTMS on Corticospinal Excitability of the Quadriceps in People With Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Device: rTMS and exercise
* Device: Sham rTMS and exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: symptomatic knee osteoarthritis primarily involving one leg based on Western Ontario and McMaster Universities Arthritis Index (WOMAC) function subscale score > 10 (out of 100 points, indicating most dysfunction) diagnosis of knee osteoarthritis opposite knee with WOMAC pain score ≤ 5. opposite knee does not have a diagnosis of knee osteoarthritis Exclusion Criteria: conditions affecting the leg other than osteoarthritis low blood pressure (< 90 systolic, 60 diastolic) or heart rate (< 60 beats per minute) conditions that limit exercise tolerance such as a heart condition pregnant or planning to become pregnant in the next 3 months conditions that alter sensation and pain processing BMI > 35 severe arthritis in both knees history of leg or back surgery in the past year or knee replacement surgery; injection in the knee joint in the past 4 weeks requires an assistive device to walk any contraindications for TMS or rTMS (seizures, metal implants in head, brain related conditions, brain injury, drug or alcohol withdrawal) medications that lower seizure threshold history of fainting spells (syncope) or low blood pressure sleep deprived inability to understand and repeat back directions regarding the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rTMS and exercise, then Sham rTMS and exercise<br>At lab visit, subjects receive repetitive transcranial magnetic stimulation (rTMS) at 10 Hz, 5 sec on, 55 sec off and quadriceps isometric exercise (5% MVIC) for 15 minutes. This is followed by a wash out period of 1 week. At the next lab visit, subjects receive sham rTMS and exercise using the same parameters. | Device: rTMS and exercise<br>* rTMS at 10 Hz (5 sec on, 55 sec off) and light quadriceps isometric exercise (5% MVIC)<br>* Other names: repetitive TMS;Device: Sham rTMS and exercise<br>* rTMS unit is on and running but mu metal is placed between the coil and the skull<br>* Other names: sham repetitive TMS;|
| Sham Comparator: Sham rTMS and exercise, then rTMS and exercise<br>At lab visit, subjects receive sham repetitive transcranial magnetic stimulation (rTMS) at 10 Hz, 5 sec on, 55 sec off and quadriceps isometric exercise (5% MVIC) for 15 minutes. This is followed by a wash out period of 1 week. At the next lab visit, subjects receive the true rTMS and exercise using the same parameters. | Device: rTMS and exercise<br>* rTMS at 10 Hz (5 sec on, 55 sec off) and light quadriceps isometric exercise (5% MVIC)<br>* Other names: repetitive TMS;Device: Sham rTMS and exercise<br>* rTMS unit is on and running but mu metal is placed between the coil and the skull<br>* Other names: sham repetitive TMS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quadriceps Central Activation Ratio (CAR) | Quadriceps Central Activation Ratio (CAR) is a percentage of the amount of torque produced during the superimposed burst technique using maximal voluntary isometric contraction (MVIC) and superimposed burst torque. It is reported on a scale of 0 (worst) to 100% (best) activation. | Within 1 hour post intervention | 
| Quadriceps Maximal Voluntary Isometric Contraction (MVIC) | HUMAC NORM electromechanical dynamometer is used to measure isometric torque generation in quadriceps muscle stabilized with 70 degrees of knee flexion. Units of measure are in Newton meters (Nm). | Within 1 hour post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Pain Rating Scale (NPRS) Score | Pain intensity is rated on a visual analog scale of 0-10 where 0 is no pain and 10 is maximum pain | Within 1 hour post intervention | 
| Pressure Pain Threshold (PPT) - Medial Knee | Using the AlgoMed algometer, pressure at a rate of 35 kPA/second is applied to the medial knee to the level that subject indicates is painful. Units of measure are kilopascal (kPa) | Within 1 hour post intervention | 
| Timed Up & Go (TUG) | Time in seconds to rise from a chair, walk 3 m, return and sit down | Within 1 hour post intervention | 
| Active Motor Threshold Motor Evoked Potential (AMT-MEP) | The quadriceps active muscle responses (motor evoked potentials) that result from the single-pulse transcranial magnetic stimulation (TMS) pulses over the motor cortex. These AMT-MEP are measured peak-to-peak in microvolts (uV ). 10 AMT-MEP values were collected and averaged. | Within 1 hour post intervention | 
| Short Interval Cortical Inhibition (SICI) | Transcranial magnetic stimulation (TMS), using the conditioning-test paired-pulse paradigm with a 3 ms interval, will be used. SICI is the ratio of the conditioning stimulus relative to the test stimulus. A ratio < 1.0 indicates inhibition. | Within 1 hour post intervention | 
| Intra Cortical Facilitation (ICF) | Transcranial magnetic stimulation (TMS), using the conditioning-test paired-pulse paradigm with a 15 ms interval, will be used. ICF is the ratio of the conditioning stimulus relative to the test stimulus. A ratio > 1.0 indicates facilitation. | Within 1 hour post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, rTMS, corticospinal, quadriceps