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CompletedNCT02881775Updated Jun 11, 2019Results posted

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

An interventional study of rTMS and exercise and Sham rTMS and exercise in Osteoarthritis, Knee, sponsored by University of North Carolina, Chapel Hill. Completed at 1 site in United States. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2019-06-11.

Sponsored by University of North Carolina, Chapel Hill · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
40 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Osteoarthritis, Knee

Keywords

  • TMS
  • rTMS
  • corticospinal
  • quadriceps
03

In context

Osteoarthritis

4,398 studies on the registry are indexed under Osteoarthritis; 582 are open to participants now.

This study's enrollment of 20 is below the median of 70 across 3,440 interventional studies indexed under Osteoarthritis.

Browse Osteoarthritis studies →

Lead sponsor

University of North Carolina, Chapel Hill is the lead sponsor of 1,340 studies on the registry; 133 are open to participants now.

Of its 155 completed or terminated interventional studies of FDA-regulated products, 136 (88%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    rTMS and exercise, then 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.

    Device: rTMS and exercise · Device: Sham rTMS and exercise

  • Sham comparator
    Sham rTMS and exercise, then 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.

    Device: rTMS and exercise · Device: Sham rTMS and exercise

Interventions

  • DevicerTMS and exercise

    rTMS at 10 Hz (5 sec on, 55 sec off) and light quadriceps isometric exercise (5% MVIC)

    Also known as: repetitive TMS

  • DeviceSham rTMS and exercise

    rTMS unit is on and running but mu metal is placed between the coil and the skull

    Also known as: sham repetitive TMS

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Within 1 hour post intervention

  2. 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).

    Time frame: Within 1 hour post intervention

Secondary outcomes

  1. 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

    Time frame: Within 1 hour post intervention

  2. 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)

    Time frame: Within 1 hour post intervention

  3. Timed Up & Go (TUG)

    Time in seconds to rise from a chair, walk 3 m, return and sit down

    Time frame: Within 1 hour post intervention

  4. 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.

    Time frame: Within 1 hour post intervention

  5. 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.

    Time frame: Within 1 hour post intervention

  6. 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.

    Time frame: Within 1 hour post intervention

07

Results

Posted May 29, 2019

Participant flow

Baseline
Participant flow — Baseline
MilestonerTMS and Exercise, Then Sham rTMS and ExerciseSham rTMS and Exercise, Then rTMS and Exercise
Started119
Completed119
Not completed00
First Intervention (1-hr Session)
Participant flow — First Intervention (1-hr Session)
MilestonerTMS and Exercise, Then Sham rTMS and ExerciseSham rTMS and Exercise, Then rTMS and Exercise
Started97
Completed97
Not completed00
Washout (1 Week)
Participant flow — Washout (1 Week)
MilestonerTMS and Exercise, Then Sham rTMS and ExerciseSham rTMS and Exercise, Then rTMS and Exercise
Started97
Completed97
Not completed00
Second Intervention (1-Hour Session)
Participant flow — Second Intervention (1-Hour Session)
MilestonerTMS and Exercise, Then Sham rTMS and ExerciseSham rTMS and Exercise, Then rTMS and Exercise
Started97
Completed97
Not completed00

Outcome measures

PrimaryQuadriceps 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.

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · % activation
Quadriceps Central Activation Ratio (CAR)
% activationrTMS and ExerciseSham rTMS and Exercise
CAR Baseline (BL)86.3554 ± 3.292186.1983 ± 3.2921
CAR BL Change-1.2496 ± 2.1397-1.2670 ± 2.1397
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = .9994 (The threshold for significance was P \<.05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. Degrees of freedom (DF) = 34.1
PrimaryQuadriceps 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).

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · Nm
Quadriceps Maximal Voluntary Isometric Contraction (MVIC)
NmrTMS and ExerciseSham rTMS and Exercise
MVIC Baseline129.46 ± 11.8464129.09 ± 11.8464
MVIC BL Change-6.3473 ± 4.4266-6.1643 ± 4.4266
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = .9768 (The threshold for statistical significance was p \< .05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. DF = 45
SecondaryNumeric 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

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · score on scale
Numeric Pain Rating Scale (NPRS) Score
score on scalerTMS and ExerciseSham rTMS and Exercise
NPRS Baseline3.25 ± .57493.000 ± .5749
NPRS BL Change-.625 ± .4187-.1570 ± .4378
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = 0.4440 (threshold for statistical significance is p \< .05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. DF = 43.1
SecondaryPressure 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)

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · kPa
Pressure Pain Threshold (PPT) - Medial Knee
kParTMS and ExerciseSham rTMS and Exercise
PPT Baseline402.41 ± 60.1780419.21 ± 60.1780
PPT BL Change21.8583 ± 28.01674.3548 ± 28.0167
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = .6608 (Threshold for statistical significance is P \< .05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. DF = 45
SecondaryTimed Up & Go (TUG)

Time in seconds to rise from a chair, walk 3 m, return and sit down

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · seconds
Timed Up & Go (TUG)
secondsrTMS and ExerciseSham rTMS and Exercise
TUG Baseline8.3919 ± .40798.3056 ± .4079
TUG BL Change-.08021 ± .803-.00542 ± .1803
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = .7706 (Threshold for statistical significance is P \< .05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. DF = 45
SecondaryActive 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.

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · uV
Active Motor Threshold Motor Evoked Potential (AMT-MEP)
uVrTMS and ExerciseSham rTMS and Exercise
AMT-MEP Baseline.1387 ± .009634.1434 ± .009634
AMT-MEP BL Change-.00007 ± .01107-.01441 ± .01107
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = .3665 (Threshold for statistical significance is P \< .05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. DF = 33
SecondaryShort 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.

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · ratio
Short Interval Cortical Inhibition (SICI)
ratiorTMS and ExerciseSham rTMS and Exercise
SICI Baseline.5140 ± .054.5996 ± .1054
SICI BL Change-.02588 ± .07227-.1151 ± .07227
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = .3889 (Threshold for statistical significance is P \< .05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. DF = 33
SecondaryIntra 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.

Time frame:
Within 1 hour post intervention
Reported as:
Least squares mean · ratio
Intra Cortical Facilitation (ICF)
ratiorTMS and ExerciseSham rTMS and Exercise
ICF Baseline1.193 ± .903.904 ± .903
ICF BL Change-.0354 ± .1896.03042 ± .1896
Statistical analysis
  • rTMS and Exercise vs Sham rTMS and Exercise · ANOVA · p = .2192 (Threshold for statistical significance is P \< .05)Repeated measures ANOVA with restricted maximum likelihood estimation and Kenward-Roger standard errors. DF = 33

Adverse events

Collected over From Baseline (Enrollment) until the end of Session 2, a total of approximately 3 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
rTMS and Exercise0/20 (0%)0/20 (0%)0/20 (0%)
Sham rTMS and Exercise0/20 (0%)0/20 (0%)0/20 (0%)

Baseline characteristics

Participants in the baseline population are the same as those in the intervention. All participants came for 3 laboratory sessions. The purpose of the first session was to collect baseline data on both the involved and uninvolved knee.

Age, Categorical
Age, Categorical(Participants)All Study Participants
<=18 years0
Between 18 and 65 years12
>=65 years8
Age, Continuous
Age, Continuous(years)All Study Participants
Mean63 ± 6.5
Sex: Female, Male
Sex: Female, Male(Participants)All Study Participants
Female14
Male6
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Study Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White19
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(Participants)All Study Participants
United States20
08

Study locations

1 site
  • University of North Carolina - Chapel Hill
    Chapel Hill, North Carolina 27599, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · May 1, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 11, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02881775
Lead sponsor
University of North Carolina, Chapel Hill
Collaborators
North Carolina Translational and Clinical Sciences Institute
Responsible party
Sponsor
First posted
Aug 29, 2016
Start date
Sep 2016
Primary completion
Jun 26, 2018
Completion
Jun 26, 2018
Results posted
May 29, 2019
Last update
Jun 11, 2019

Study contacts

Deborah L Givens, PhD
principal investigator · University of North Carolina, Chapel Hill

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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