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

Not Applicable

Completed

Conditions: Osteoarthritis, Knee

Interventions: Device: rTMS and exercise
Device: Sham rTMS and exercise

Registration Number: NCT02881775

Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
rTMS and exercise, then Sham rTMS and exercise	rTMS and exercise	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.
rTMS and exercise, then Sham rTMS and exercise	Sham rTMS and exercise	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.
Sham rTMS and exercise, then rTMS and exercise	rTMS and exercise	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.
Sham rTMS and exercise, then rTMS and exercise	Sham rTMS and exercise	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.

Primary Outcome Measures

Name	Time	Method
Quadriceps Maximal Voluntary Isometric Contraction (MVIC)	Within 1 hour post intervention	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).
Quadriceps Central Activation Ratio (CAR)	Within 1 hour post intervention	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.

Secondary Outcome Measures

Name	Time	Method
Numeric Pain Rating Scale (NPRS) Score	Within 1 hour post intervention	Pain intensity is rated on a visual analog scale of 0-10 where 0 is no pain and 10 is maximum pain
Pressure Pain Threshold (PPT) - Medial Knee	Within 1 hour post intervention	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)
Timed Up & Go (TUG)	Within 1 hour post intervention	Time in seconds to rise from a chair, walk 3 m, return and sit down
Active Motor Threshold Motor Evoked Potential (AMT-MEP)	Within 1 hour post intervention	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.
Short Interval Cortical Inhibition (SICI)	Within 1 hour post intervention	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.
Intra Cortical Facilitation (ICF)	Within 1 hour post intervention	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.