Ischemic Stroke
Conditions
Keywords
Stroke, rTMS, Motor rehabilitation
Brief summary
A prospective, multi-center, randomized, sham-controlled, blinded study combining active Nexstim NBS-guided 1Hz rTMS or sham-rTMS targeting the healthy hemisphere with standardized task oriented rehabilitation will be conducted in patients with post-stroke motor impairment of the upper limb. The therapy will be provided for 6 weeks and primary outcome assessed 6 months later.
Interventions
DEVICENexstim NBS guided active rTMS
Nexstim NBS guided active rTMS + standardized task-oriented therapy
DEVICENexstim NBS guided sham rTMS
Nexstim NBS guided sham rTMS + standardized task-oriented therapy
Sponsors
Nexstim Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age * An ischemic stroke suffered 3-12 months prior to the study * No other known brain abnormalities by history; * A one-sided stroke resulting in upper extremity paresis * A Chedoke-McMaster Stroke Assessment arm stage and hand stage of 3-6 for the affected limb
Exclusion criteria
* Implanted metallic parts of implanted electronic devices, including pacemakers, defibrillators, or implant medication pump; * Pregnant or trying to become pregnant; Lack of pregnancy established in females of child-bearing potential by a negative urine pregnancy test at screening. * Active alcohol abuse, illicit drug use or drug abuse or significant mental illness * Patients suffering from depression as measured by a score of \>10 on the Patient Health Questionnaire (PHQ9). For clarity, patients diagnosed with depression which is controlled with stable anti-depressive medication and in whom PHQ9 is \<10 are eligible to participate in the trial. * History of epilepsy, defined as at least two unprovoked seizures occurring greater than 24 hours apart or diagnosis of an epilepsy syndrome, OR a seizure within the last 12 months. * Any condition that would prevent the subject from giving voluntary informed consent; * An implanted brain stimulator; * Any metal in head with the exception of dental work or any ferromagnetic metal -elsewhere in the body; * Enrolled or plans to enroll in an interventional trial during this study; * Scalp wounds or infections; * Claustrophobia precluding MRI; * A fixed contraction deformity in the affected limb that would prevent normal dexterity if patient were neurologically intact; * Excessive spasticity as indicated by the Modified Ashworth Spasticity (MAS) Scale \>2/4 in either elbow flexors, wrist flexors or finger flexors of the affected limb; * Previous stroke with residual deficits (TIAs not a reason for exclusion); * Premorbid (retrospective) modified Rankin Scale (mRS) score ≥2 of any aetiology; * A concurrent progressive neurologic disorder, acute coronary syndrome, severe heart disease (NYHA Classification \> 3), or other major medical condition, * Confirmed or suspected lower-limb fracture preventing mobilization, patients requiring palliative care * Patients planning to undergo any other occupational therapy during the 6 week active treatment period of the trial (see section 5.2 for study schedule) than what is provided in the study * A recent injection of botulinium toxin to the affected upper limb in the last 3 months, or the need of an injection of botulinum toxin anytime during the study period and follow up. * A recent injection of phenol to the affected upper limb in the last 6 months, or the need of an injection of phenol anytime during the study period and follow up. * Ataxia as measured by a score \> 1 on item 7 (limb ataxia) of the NIH stroke scale. * Severe sensory deficits as measured by a score of 2 on item 8 of the NIH stroke scale. * Severe aphasia as measured by a score of \> 2 on item 9 (best language) of the NIH stroke scale. * Severe neglect as measured by a score of 2 on item 11 (extinction and inattention) of the NIH stroke scale. * Patients unable to comprehend or follow verbal commands * Based on PI's or local physician's assessment patient unable to tolerate the trial procedure due to medical condition * A Mini mental status exam (MMSE) \<25.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Upper Extremity Fugl-Meyer Score | Change from baseline to 6 months after end of treatment. | Range 0 to 65. HIgher scores indicate better function. Minimal clinically important difference = change of 5 points or more on scale. Outcome measure = proportion of patients in treatment arm gaining at least 5 points on scale between baseline and 6 months after end of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Upper Extremity Fugl-Meyer Score | Change in score from baseline to 6 months after end of treatment | Range 0-65. HIgher scores indicate better function. |
| Arm-Research Action Test (ARAT) | Change in score from baseline to 6 months after end of treatment. | Range 0 to 57. Higher scores indicate better function. |
| NIH Stroke Scale (NIHSS) | Change in score from baseline to 6 months after end of treatment | National Institute of Health Stroke Scale - Motor Arm. Range 0 to 4. Lower score indicates better function. |
| Quality of Life Assessment: EQ-5D | Change in score from baseline to 6 months after end of treatment | EuroQoL - EQ-5D score. Range 0 to 100. HIgher numbers indicate better quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy | 31 |
| Control Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy | 29 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Active | Total | Control |
|---|---|---|---|
| Action Research Arm Test | 28.9 units on a scale STANDARD_DEVIATION 17.7 | 31.7 units on a scale STANDARD_DEVIATION 17.3 | 34.7 units on a scale STANDARD_DEVIATION 16.7 |
| Age, Continuous | 59.0 years STANDARD_DEVIATION 9.5 | 58.5 years STANDARD_DEVIATION 10.2 | 58.0 years STANDARD_DEVIATION 10.9 |
| EQ-5D | 61.8 units on a scale STANDARD_DEVIATION 19.9 | 65.8 units on a scale STANDARD_DEVIATION 19.5 | 70.1 units on a scale STANDARD_DEVIATION 18.4 |
| NIHSS | 2.23 units on a scale STANDARD_DEVIATION 1.74 | 2.05 units on a scale STANDARD_DEVIATION 1.8 | 1.86 units on a scale STANDARD_DEVIATION 1.88 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 15 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 44 Participants | 20 Participants |
| Sex: Female, Male Female | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Male | 23 Participants | 42 Participants | 19 Participants |
| Time from stroke 3-6 months | 15 Participants | 27 Participants | 12 Participants |
| Time from stroke 6-12 months | 16 Participants | 33 Participants | 17 Participants |
| Upper extremity Fugl-Meyer score | 37.4 units on a scale STANDARD_DEVIATION 12.7 | 39.7 units on a scale STANDARD_DEVIATION 13.1 | 42.2 units on a scale STANDARD_DEVIATION 13.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 28 |
| other Total, other adverse events | 5 / 30 | 2 / 28 |
| serious Total, serious adverse events | 4 / 30 | 5 / 28 |
Outcome results
Primary
Upper Extremity Fugl-Meyer Score
Range 0 to 65. HIgher scores indicate better function. Minimal clinically important difference = change of 5 points or more on scale. Outcome measure = proportion of patients in treatment arm gaining at least 5 points on scale between baseline and 6 months after end of treatment.
Time frame: Change from baseline to 6 months after end of treatment.
Population: Intent to treat population. All subjects completing the baseline visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Upper Extremity Fugl-Meyer Score | 18 Participants |
| Control | Upper Extremity Fugl-Meyer Score | 14 Participants |
p-value: 0.62Chi-squared, Corrected
Secondary
Arm-Research Action Test (ARAT)
Range 0 to 57. Higher scores indicate better function.
Time frame: Change in score from baseline to 6 months after end of treatment.
Population: Intent to treat population. All subjects completing the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Arm-Research Action Test (ARAT) | 4.93 units on a scale | Standard Deviation 6.99 |
| Control | Arm-Research Action Test (ARAT) | 5.68 units on a scale | Standard Deviation 7.96 |
p-value: 0.54Wilcoxon (Mann-Whitney)
Secondary
NIH Stroke Scale (NIHSS)
National Institute of Health Stroke Scale - Motor Arm. Range 0 to 4. Lower score indicates better function.
Time frame: Change in score from baseline to 6 months after end of treatment
Population: Intent to treat. All subject completing the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | NIH Stroke Scale (NIHSS) | -0.62 units on a scale | Standard Deviation 1.35 |
| Control | NIH Stroke Scale (NIHSS) | -0.50 units on a scale | Standard Deviation 1.4 |
p-value: 0.59Wilcoxon (Mann-Whitney)
Secondary
Quality of Life Assessment: EQ-5D
EuroQoL - EQ-5D score. Range 0 to 100. HIgher numbers indicate better quality of life.
Time frame: Change in score from baseline to 6 months after end of treatment
Population: Intent to treat - all subjects completing the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Quality of Life Assessment: EQ-5D | 9.86 units on a scale | Standard Deviation 21.09 |
| Control | Quality of Life Assessment: EQ-5D | 8.96 units on a scale | Standard Deviation 18.8 |
p-value: 0.7Wilcoxon (Mann-Whitney)
Secondary
Upper Extremity Fugl-Meyer Score
Range 0-65. HIgher scores indicate better function.
Time frame: Change in score from baseline to 6 months after end of treatment
Population: Intent to treat population. All enrolled subjects who completed the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Upper Extremity Fugl-Meyer Score | 5.17 units on a scale | Standard Deviation 8.24 |
| Control | Upper Extremity Fugl-Meyer Score | 5.00 units on a scale | Standard Deviation 7.29 |
p-value: 0.46Wilcoxon (Mann-Whitney)