Spasticity
Conditions
Keywords
Post-Stroke Spasticity
Brief summary
Spasticity is a common complication of stroke affecting quality of life. Spasticity involves exaggerated stretch reflexes that create stiffness in muscles with associated loss of motion and functional control. Traditional treatments involve range of motion, medications, and sometimes surgery. Each of these has its own limitations, which has invited exploration of alternative modes of treatment. One such treatment with the potential to benefit spasticity is repetitive Transcranial Magnetic Stimulation (rTMS). The purpose of this study is to determine whether patients with upper limb spasticity as a consequence of a chronic stroke can benefit from stimulation of the non-affected hemisphere of the brain with low-frequency (inhibitory) repetitive Transcranial Magnetic Stimulation (rTMS), potentially leading to a reduction of spasticity and clinical improvement in upper limb function.
Detailed description
The purpose of this pilot study is to evaluate the efficacy of rTMS versus placebo for spasticity reduction in a cross-over design in 6 people with stroke. Our research question is: In patients with upper extremity spasticity as a consequence of chronic stroke, does stimulation of the contralesional motor cortex with low-frequency (inhibitory) rTMS lead to reduction of spasticity and thereby clinical improvement in upper extremity function? Our rationale is that the pathophysiology of post-stroke spasticity is primarily driven by ensuant cortical derangement, and further, that this derangement can be mitigated to a clinically meaningful extent by proper utilization of rTMS directed at these foci. Optimized rTMS treatment protocols may even achieve efficacy that surpasses current mainstays of spasticity management. Patients will be randomly assigned to receive either rTMS or placebo during their first treatment arm and then cross-over to receive the opposite treatment at the second treatment arm. A washout period of one month will occur between treatment arms. Each treatment arm will consist of 3 daily treatment sessions. Participants will present on a Monday for the pre-test assessment, Tuesday-Thursday for the treatment sessions and Friday for the post-test assessment. One treatment session will consist of 600 pulses of 1Hertz rTMS at an intensity of 90% of resting motor threshold (duration 10 minutes) applied to the primary motor area of the contralesional hemisphere. Sham rTMS intensity will be 0% but with a similar sound and scalp sensation. Assessments will be made at each session, and will be conducted at pre-test, post-test, and one-month follow-up. The one month follow-up test will serve as the pretest for the next treatment arm. That is, after follow-up, patients will cross-over to receive the opposite treatment in the same format. Safety has already been demonstrated for our protocol. Data will be analyzed with methods appropriate to a single-subject crossover design (visual analysis, confidence intervals and 2-Standard Deviation bandwidth). The primary outcome that we will measure is reduction of spasticity at the fingers and wrist. A secondary outcome of interest is functional improvement of the spastic upper limb.
Interventions
DEVICErepetitive Transcranial Magnetic Stimulation (rTMS)
The treatment arm will consist of 3 daily treatment sessions. One treatment session in this study with real rTMS will consist of 600 pulses of 1Hertz rTMS at an intensity of 90% of resting motor threshold (duration 10 minutes) applied to the primary motor area of the contralesional hemisphere.
DEVICESham repetitive Transcranial Magnetic Stimulation
Sham rTMS utilizes a coil that produces identical noise and tactile sensation to the real coil, but does not emit a magnetic field (0% intensity). Duration and frequency of auditory and tactile stimulation will be identical to the real intervention.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. first-time stroke 2. stroke at least six months prior to onset of study with chronic sequela of spasticity 3. stroke location- either cortical or subcortical 4. stroke type- either hemorrhagic or ischemic 5. stroke hemisphere- either left or right, dominant or non- dominant hemisphere 6. 18 years of age or older 7. gender- either male or female 8. ability to follow three-step directions 9. demonstration of 10 degrees of active extension at the metacarpophalangeal joint and wrist of the paretic upper extremity 10. demonstration of consistent resting motor evoked potential from ipsilesional and contralesional hemispheres 11. sufficient ambulation or wheelchair mobility to allow subject to present to treatment and testing areas with minimum assist
Exclusion criteria
1. history of seizure within the past two years 2. inability to follow three-step directions 3. anosognosia 4. moderate to severe receptive aphasia 5. inability to give informed consent 6. premorbid spasticity or neurologic impairment prior to stroke 7. co-morbidities impairing upper extremity function such as fracture or deformity 8. indwelling metal or medical devices incompatible with TMS 9. pregnancy 10. bi-hemispheric or multifocal stroke 11. dementia 12. neurolytic injection within the 3 months prior to onset of study or planned neurolytic injection during study period 13. planned vacation or travel during study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Contralesional Corticospinal Excitability | From Day 1 to Day 5 | Motor evoked potentials (MEPs) were measured using surface EMG. The average amplitude of 10 MEPs measured at baseline was compared to the average of 10 MEPs measured at post-test and this difference is recorded as the change in corticospinal excitability. A greater negative value would indicate larger post-test MEPs and increased corticospinal excitability. |
| Change From Baseline Finger Tracking Score | From Day 1 to Day 5 | An electrogoniometer attached to the hand was used to measure index finger movement. Patients tracked a sine wave that ranged from 85% to 15% of their individual max range of motion which does impact the accuracy measure scale. Accuracy of tracking along with the target waveform was assessed on a scale ranging from -100 to 100 (100 being perfect accuracy). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stroke Impact Scale | From Day 1 to Day 5 | Change from baseline stroke impact scale score The Stroke Impact Scale (SIS) is a standardized self-reported questionnaire used to assess the impact of stoke on an individual's quality of life. Scores range from 0-100 with higher scores indicating greater functionality and quality of life. |
| Change From Baseline Resting Motor Threshold | From Day 1 to Day 5 | Average change from baseline resting motor threshold The resting motor threshold (RMT) is the lowest possible stimulator output (% maximal stimulator output) required to reliably elicit a motor evoked potential. A lower RMT would indicate increased corticospinal excitability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rTMS Then Sham rTMS repetitive Transcranial Magnetic Stimulation (rTMS)
repetitive Transcranial Magnetic Stimulation (rTMS): The treatment arm will consist of 3 daily treatment sessions. One treatment session in this study with real rTMS will consist of 600 pulses of 1Hertz rTMS at an intensity of 90% of resting motor threshold (duration 10 minutes) applied to the primary motor area of the contralesional hemisphere. | 2 |
| Sham rTMS Then Real rTMS Sham repetitive Transcranial Magnetic Stimulation (Sham rTMS)
Sham repetitive Transcranial Magnetic Stimulation: Sham rTMS utilizes a coil that produces identical noise and tactile sensation to the real coil, but does not emit a magnetic field (0% intensity). Duration and frequency of auditory and tactile stimulation will be identical to the real intervention. | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | rTMS Then Sham rTMS | Sham rTMS Then Real rTMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Change From Baseline Contralesional Corticospinal Excitability
Motor evoked potentials (MEPs) were measured using surface EMG. The average amplitude of 10 MEPs measured at baseline was compared to the average of 10 MEPs measured at post-test and this difference is recorded as the change in corticospinal excitability. A greater negative value would indicate larger post-test MEPs and increased corticospinal excitability.
Time frame: From Day 1 to Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rTMS | Change From Baseline Contralesional Corticospinal Excitability | 67.88 microVolts | Standard Deviation 384.91 |
| Real rTMS | Change From Baseline Contralesional Corticospinal Excitability | -37.23 microVolts | Standard Deviation 542.11 |
Primary
Change From Baseline Finger Tracking Score
An electrogoniometer attached to the hand was used to measure index finger movement. Patients tracked a sine wave that ranged from 85% to 15% of their individual max range of motion which does impact the accuracy measure scale. Accuracy of tracking along with the target waveform was assessed on a scale ranging from -100 to 100 (100 being perfect accuracy).
Time frame: From Day 1 to Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rTMS | Change From Baseline Finger Tracking Score | 11.95 score on a scale | Standard Deviation 29.65 |
| Real rTMS | Change From Baseline Finger Tracking Score | 8.01 score on a scale | Standard Deviation 27.18 |
Secondary
Change From Baseline Resting Motor Threshold
Average change from baseline resting motor threshold The resting motor threshold (RMT) is the lowest possible stimulator output (% maximal stimulator output) required to reliably elicit a motor evoked potential. A lower RMT would indicate increased corticospinal excitability.
Time frame: From Day 1 to Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rTMS | Change From Baseline Resting Motor Threshold | -2.25 %MSO | Standard Deviation 4.49 |
| Real rTMS | Change From Baseline Resting Motor Threshold | -3.75 %MSO | Standard Deviation 12.6 |
Secondary
Change in Stroke Impact Scale
Change from baseline stroke impact scale score The Stroke Impact Scale (SIS) is a standardized self-reported questionnaire used to assess the impact of stoke on an individual's quality of life. Scores range from 0-100 with higher scores indicating greater functionality and quality of life.
Time frame: From Day 1 to Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rTMS | Change in Stroke Impact Scale | -0.25 score on a scale | Standard Deviation 0.433 |
| Real rTMS | Change in Stroke Impact Scale | -0.5 score on a scale | Standard Deviation 0.87 |