Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Post-Stroke Spasticity

Not Applicable

Completed

Conditions: Spasticity

Interventions: Device: Sham repetitive Transcranial Magnetic Stimulation
Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Registration Number: NCT02268461

Lead Sponsor: University of Minnesota

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 4

Inclusion Criteria

first-time stroke
stroke at least six months prior to onset of study with chronic sequela of spasticity
stroke location- either cortical or subcortical
stroke type- either hemorrhagic or ischemic
stroke hemisphere- either left or right, dominant or non- dominant hemisphere
18 years of age or older
gender- either male or female
ability to follow three-step directions
demonstration of 10 degrees of active extension at the metacarpophalangeal joint and wrist of the paretic upper extremity
demonstration of consistent resting motor evoked potential from ipsilesional and contralesional hemispheres
sufficient ambulation or wheelchair mobility to allow subject to present to treatment and testing areas with minimum assist

Exclusion Criteria

history of seizure within the past two years
inability to follow three-step directions
anosognosia
moderate to severe receptive aphasia
inability to give informed consent
premorbid spasticity or neurologic impairment prior to stroke
co-morbidities impairing upper extremity function such as fracture or deformity
indwelling metal or medical devices incompatible with TMS
pregnancy
bi-hemispheric or multifocal stroke
dementia
neurolytic injection within the 3 months prior to onset of study or planned neurolytic injection during study period
planned vacation or travel during study period

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sham rTMS	Sham repetitive Transcranial Magnetic Stimulation	Sham repetitive Transcranial Magnetic Stimulation (Sham rTMS)
rTMS	repetitive Transcranial Magnetic Stimulation (rTMS)	repetitive Transcranial Magnetic Stimulation (rTMS)

Primary Outcome Measures

Name	Time	Method
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).
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.

Secondary Outcome Measures

Name	Time	Method
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.
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.