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| Name | Class |
|---|---|
| North Carolina Translational and Clinical Sciences Institute | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rTMS and exercise, then Sham rTMS and exercise | Experimental | 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. |
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| Sham rTMS and exercise, then rTMS and exercise | Sham Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rTMS and exercise | Device | rTMS at 10 Hz (5 sec on, 55 sec off) and light quadriceps isometric exercise (5% MVIC) |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Deborah L Givens, PhD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina - Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. rTMS and exercise: rTMS at 10 Hz (5 sec on, 55 sec off) and light quadriceps isometric exercise (5% MVIC) Sham rTMS and exercise: rTMS unit is on and running but mu metal is placed between the coil and the skull |
| FG001 | 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. rTMS and exercise: rTMS at 10 Hz (5 sec on, 55 sec off) and light quadriceps isometric exercise (5% MVIC) Sham rTMS and exercise: rTMS unit is on and running but mu metal is placed between the coil and the skull |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline |
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| First Intervention (1-hr Session) |
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| Washout (1 Week) |
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| Second Intervention (1-Hour Session) |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants who were randomized to receive either rTMS and exercise or sham rTMS and exercise. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. Four subjects declined to perform the test after the experience with the electrical stimulus in the baseline session. | Posted | Least Squares Mean | Standard Error | % activation | Within 1 hour post intervention |
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From Baseline (Enrollment) until the end of Session 2, a total of approximately 3 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Deborah Givens, PhD | University of North Carolina at Chapel Hill | 919-843-8660 | deborah_givens@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 1, 2019 | May 1, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| D005081 | Exercise Therapy |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
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| Sham rTMS and exercise | Device | rTMS unit is on and running but mu metal is placed between the coil and the skull |
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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 |
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| Participants |
| No |
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| Age, Continuous | intake questionnaire | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| OG001 | 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. |
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| Primary | 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). | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. | Posted | Least Squares Mean | Standard Error | Nm | Within 1 hour post intervention |
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| Secondary | 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 | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. For two subjects, the research assistant missed obtaining the post-intervention pain rating. | Posted | Least Squares Mean | Standard Error | score on scale | Within 1 hour post intervention |
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| Secondary | 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) | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. | Posted | Least Squares Mean | Standard Error | kPa | Within 1 hour post intervention |
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| Secondary | Timed Up & Go (TUG) | Time in seconds to rise from a chair, walk 3 m, return and sit down | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. | Posted | Least Squares Mean | Standard Error | seconds | Within 1 hour post intervention |
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| Secondary | 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. | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. A technical issue in how the TMS unit worked was discovered after collecting the first 4 subjects in the intervention part of the study. This impacted their AMT-MEP, ICF, and SICI data which were excluded from the analyses. | Posted | Least Squares Mean | Standard Error | uV | Within 1 hour post intervention |
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| Secondary | 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. | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. A technical issue in how the TMS unit worked was discovered after collecting the first 4 subjects in the intervention part of the study. This impacted their AMT-MEP, ICF, and SICI data which were excluded from the analyses. | Posted | Least Squares Mean | Standard Error | ratio | Within 1 hour post intervention |
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| Secondary | 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. | 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study. A technical issue in how the TMS unit worked was discovered after collecting the first 4 subjects in the intervention part of the study. This impacted their AMT-MEP, ICF, and SICI data which were excluded from the analyses. | Posted | Least Squares Mean | Standard Error | ratio | Within 1 hour post intervention |
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| 0 |
| 20 |
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | 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. | 0 | 20 | 0 | 20 | 0 | 20 |
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| D012216 |
| Rheumatic Diseases |
| D003266 |
| Continuity of Patient Care |
| D005791 | Patient Care |
| D026741 | Physical Therapy Modalities |