search
Back to results

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

Primary Purpose

Osteoarthritis, Knee

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
rTMS and exercise
Sham rTMS and exercise
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring TMS, rTMS, corticospinal, quadriceps

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of North Carolina - Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

rTMS and exercise, then Sham rTMS and exercise

Sham rTMS and exercise, then rTMS and exercise

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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).

Secondary Outcome Measures

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
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)
Timed Up & Go (TUG)
Time in seconds to rise from a chair, walk 3 m, return and sit down
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.
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.
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.

Full Information

First Posted
August 15, 2016
Last Updated
May 28, 2019
Sponsor
University of North Carolina, Chapel Hill
Collaborators
North Carolina Translational and Clinical Sciences Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT02881775
Brief Title
Immediate Effects of rTMS on Excitability of the Quadriceps With Knee Osteoarthritis
Official Title
Immediate Effects of rTMS on Corticospinal Excitability of the Quadriceps in People With Knee Osteoarthritis
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
June 26, 2018 (Actual)
Study Completion Date
June 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
North Carolina Translational and Clinical Sciences Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
TMS, rTMS, corticospinal, quadriceps

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rTMS and exercise, then Sham rTMS and exercise
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham rTMS and exercise, then rTMS and exercise
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
rTMS and exercise
Other Intervention Name(s)
repetitive TMS
Intervention Description
rTMS at 10 Hz (5 sec on, 55 sec off) and light quadriceps isometric exercise (5% MVIC)
Intervention Type
Device
Intervention Name(s)
Sham rTMS and exercise
Other Intervention Name(s)
sham repetitive TMS
Intervention Description
rTMS unit is on and running but mu metal is placed between the coil and the skull
Primary Outcome Measure Information:
Title
Quadriceps Central Activation Ratio (CAR)
Description
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.
Time Frame
Within 1 hour post intervention
Title
Quadriceps Maximal Voluntary Isometric Contraction (MVIC)
Description
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).
Time Frame
Within 1 hour post intervention
Secondary Outcome Measure Information:
Title
Numeric Pain Rating Scale (NPRS) Score
Description
Pain intensity is rated on a visual analog scale of 0-10 where 0 is no pain and 10 is maximum pain
Time Frame
Within 1 hour post intervention
Title
Pressure Pain Threshold (PPT) - Medial Knee
Description
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)
Time Frame
Within 1 hour post intervention
Title
Timed Up & Go (TUG)
Description
Time in seconds to rise from a chair, walk 3 m, return and sit down
Time Frame
Within 1 hour post intervention
Title
Active Motor Threshold Motor Evoked Potential (AMT-MEP)
Description
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.
Time Frame
Within 1 hour post intervention
Title
Short Interval Cortical Inhibition (SICI)
Description
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.
Time Frame
Within 1 hour post intervention
Title
Intra Cortical Facilitation (ICF)
Description
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.
Time Frame
Within 1 hour post intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deborah L Givens, PhD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs