Trial Outcomes & Findings for Immediate Effects of rTMS on Excitability of the Quadriceps With Knee Osteoarthritis (NCT NCT02881775)

NCT ID: NCT02881775

Last Updated: 2019-06-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

20 participants

Primary outcome timeframe

Within 1 hour post intervention

Results posted on

2019-06-11

Participant Flow

Participant milestones

Participant milestones
Measure
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
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
Baseline
STARTED
11
9
Baseline
COMPLETED
11
9
Baseline
NOT COMPLETED
0
0
First Intervention (1-hr Session)
STARTED
9
7
First Intervention (1-hr Session)
COMPLETED
9
7
First Intervention (1-hr Session)
NOT COMPLETED
0
0
Washout (1 Week)
STARTED
9
7
Washout (1 Week)
COMPLETED
9
7
Washout (1 Week)
NOT COMPLETED
0
0
Second Intervention (1-Hour Session)
STARTED
9
7
Second Intervention (1-Hour Session)
COMPLETED
9
7
Second Intervention (1-Hour Session)
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Study Participants
n=20 Participants
Participants who were randomized to receive either rTMS and exercise or sham rTMS and exercise.
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
12 Participants
n=5 Participants
Age, Categorical
>=65 years
8 Participants
n=5 Participants
Age, Continuous
63 years
STANDARD_DEVIATION 6.5 • n=5 Participants
Sex: Female, Male
Female
14 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=5 Participants
Race (NIH/OMB)
White
19 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
20 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Within 1 hour post intervention

Population: 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.

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.

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=12 Participants
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
n=12 Participants
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.
Quadriceps Central Activation Ratio (CAR)
CAR Baseline (BL)
86.3554 % activation
Standard Error 3.2921
86.1983 % activation
Standard Error 3.2921
Quadriceps Central Activation Ratio (CAR)
CAR BL Change
-1.2496 % activation
Standard Error 2.1397
-1.2670 % activation
Standard Error 2.1397

PRIMARY outcome

Timeframe: Within 1 hour post intervention

Population: 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study.

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).

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=16 Participants
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
n=16 Participants
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.
Quadriceps Maximal Voluntary Isometric Contraction (MVIC)
MVIC Baseline
129.46 Nm
Standard Error 11.8464
129.09 Nm
Standard Error 11.8464
Quadriceps Maximal Voluntary Isometric Contraction (MVIC)
MVIC BL Change
-6.3473 Nm
Standard Error 4.4266
-6.1643 Nm
Standard Error 4.4266

SECONDARY outcome

Timeframe: Within 1 hour post intervention

Population: 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.

Pain intensity is rated on a visual analog scale of 0-10 where 0 is no pain and 10 is maximum pain

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=16 Participants
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
n=14 Participants
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.
Numeric Pain Rating Scale (NPRS) Score
NPRS BL Change
-.625 score on scale
Standard Error .4187
-.1570 score on scale
Standard Error .4378
Numeric Pain Rating Scale (NPRS) Score
NPRS Baseline
3.25 score on scale
Standard Error .5749
3.000 score on scale
Standard Error .5749

SECONDARY outcome

Timeframe: Within 1 hour post intervention

Population: 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study.

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)

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=16 Participants
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
n=16 Participants
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.
Pressure Pain Threshold (PPT) - Medial Knee
PPT Baseline
402.41 kPa
Standard Error 60.1780
419.21 kPa
Standard Error 60.1780
Pressure Pain Threshold (PPT) - Medial Knee
PPT BL Change
21.8583 kPa
Standard Error 28.0167
4.3548 kPa
Standard Error 28.0167

SECONDARY outcome

Timeframe: Within 1 hour post intervention

Population: 4 subjects withdrew from the study after the baseline measures. This left 16 subjects for the intervention arm of the study.

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

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=16 Participants
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
n=16 Participants
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.
Timed Up & Go (TUG)
TUG Baseline
8.3919 seconds
Standard Error .4079
8.3056 seconds
Standard Error .4079
Timed Up & Go (TUG)
TUG BL Change
-.08021 seconds
Standard Error .803
-.00542 seconds
Standard Error .1803

SECONDARY outcome

Timeframe: Within 1 hour post intervention

Population: 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.

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.

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=12 Participants
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
n=12 Participants
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.
Active Motor Threshold Motor Evoked Potential (AMT-MEP)
AMT-MEP Baseline
.1387 uV
Standard Error .009634
.1434 uV
Standard Error .009634
Active Motor Threshold Motor Evoked Potential (AMT-MEP)
AMT-MEP BL Change
-.00007 uV
Standard Error .01107
-.01441 uV
Standard Error .01107

SECONDARY outcome

Timeframe: Within 1 hour post intervention

Population: 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.

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.

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=12 Participants
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
n=12 Participants
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.
Short Interval Cortical Inhibition (SICI)
SICI Baseline
.5140 ratio
Standard Error .054
.5996 ratio
Standard Error .1054
Short Interval Cortical Inhibition (SICI)
SICI BL Change
-.02588 ratio
Standard Error .07227
-.1151 ratio
Standard Error .07227

SECONDARY outcome

Timeframe: Within 1 hour post intervention

Population: 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.

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.

Outcome measures

Outcome measures
Measure
rTMS and Exercise
n=12 Participants
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
n=12 Participants
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.
Intra Cortical Facilitation (ICF)
ICF BL Change
-.0354 ratio
Standard Error .1896
.03042 ratio
Standard Error .1896
Intra Cortical Facilitation (ICF)
ICF Baseline
1.193 ratio
Standard Error .903
.904 ratio
Standard Error .903

Adverse Events

rTMS and Exercise

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Sham rTMS and Exercise

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Deborah Givens, PhD

University of North Carolina at Chapel Hill

Phone: 919-843-8660

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place