Clinical trial NCT02268461: Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Post-Stroke Spasticity
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Post-Stroke Spasticity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spasticity
Keywords: Post-Stroke Spasticity
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2014-10-20
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline Contralesional Corticospinal Excitability
timeFrame: From Day 1 to Day 5
measure: Change From Baseline Finger Tracking Score
timeFrame: From Day 1 to Day 5
Secondary outcomes:
measure: Change in Stroke Impact Scale
timeFrame: From Day 1 to Day 5
measure: Change From Baseline Resting Motor Threshold
timeFrame: From Day 1 to Day 5
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota, Clinical and Translational Science Institute
state: Minnesota
Study officials:
affiliation: University of Minnesota, Physical Medicine and Rehabilitation
name: Matthew J Timp, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota, Program in Physical Therapy
name: James R Carey, PhD, PT
role: STUDY_CHAIR
affiliation: University of Minnesota, Physical Medicine and Rehabilitation
name: Florence S John, MD, MPH
role: STUDY_DIRECTOR
affiliation: University of Minnesota, Program in Physical Therapy
name: Kate Frost, MS
role: STUDY_DIRECTOR
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