Cerebrovascular Accident (CVA), Hemiparesis, Muscle Spasticity, Spasticity as Sequela of Stroke, Stroke, Upper Extremity Paralysis
Conditions
Keywords
stroke, CVA, Spasticity, hemiparesis, rehabilitation, trans-spinal direct current stimulation (tsDCS), non-invasive stimulation
Brief summary
The purpose of this study is to evaluate if 5 consecutive sessions of PathMaker anodal DoubleStim treatment, which combines non-invasive stimulation of the spinal cord (tsDCS- trans-spinal direct current stimulation) and of the median nerve at the peripheral wrist (pDCS-- peripheral direct current stimulation), can significantly reduce spasticity of the wrist and hand after stroke.
Interventions
DEVICEsham Doublestim
PathMaker MyoRegulator device
DEVICEanodal Doublestim
PathMaker MyoRegulator device
Sponsors
PathMaker Neurosystems Inc.
Dr. Zaghloul Ahmed
Northwell Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
The sham stimulation condition preceded the anodal stimulation condition for all participants, and subjects were told they would receive both conditions, but were blinded to order of assignment.
Intervention model description
All participants received both stimulation conditions (sham Doublestim and anodal Doublestim), separated by a 1-week washout period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. First single focal unilateral hemisphere lesion with diagnosis verified by brain imaging (MRI or CT scans) that occurred at least 6 months prior 2. Cognitive function sufficient to understand the experiments and follow instructions 3. A Modified Ashworth Scale score between 1-3 points for wrist flexor and extensor muscles 4. A minimum of 15 degrees wrist passive range of motion (ROM) for wrist flexion and extension from wrist neutral position
Exclusion criteria
1. Focal brainstem or thalamic infarcts 2. Prior surgical treatments for spasticity of the upper limb 3. Ongoing use of central nervous system (CNS)-active medications 4. Ongoing use of psychoactive medications, such as stimulants, antidepressants, and anti-psychotic medications 5. Botox or phenol alcohol treatment within 12 weeks of enrollment 6. Pregnancy in women, as determined by self-report 7. History of spinal cord injury or weakness 8. Chronic pain 9. Peripheral neuropathy including insulin dependent diabetes as determined by case history 10. Presence of additional potential tsDCS risk factors: * Damaged skin at the site of stimulation (i.e., skin with ingrown hairs, acne, razor nicks, wounds that have not healed recent scar tissue, broken skin, etc.) * Presence of an electrically, magnetically or mechanically activated implant (including cardiac pacemaker), an intracerebral vascular clip, or any other electrically sensitive support system * Highly conductive metal in any part of the body, including metal injury to the eye (jewelry must be removed during stimulation) * Past history of seizures or unexplained spells of loss of consciousness during the previous 36 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Area Under the Curve for Objectively Measured Spastic Catch Response of the Wrist Flexors at Fast Speed | baseline, final session at day 5, 1 week FU | Subjects' wrists were passively extended at fast speed by a stepper motor to induce a spastic catch response, and its resistance torque was calculated in Newton meters (Nm). Mean percent change from baseline in the area under the curve for the resistance torque were compared across two timepoints (final session at day 5 and 1 week follow-up) in two conditions (sham vs. anodal Doublestim) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Modified Tardieu Scale (MTS) Score | baseline, final session at day 5, 1 week FU | The Modified Tardieu Scale (MTS) quantifies muscle spasticity for each joint at slow and fast velocities on a 0-5 point scale. MTS scores at fast velocity were summed across 11 joints of the upper extremity (for a total of 0-55 points), with lower scores indicating improved spasticity. Mean summed MTS scores (out of 55 total points) were compared across two timepoints (final session at day 5 and 1 week FU) in two conditions (sham vs. anodal Doublestim). |
Countries
United States
Participant flow
Pre-assignment details
All participants received both the anodal and sham trans-spinal direct current stimulation + peripheral direct current stimulation (tsDCS + pDCS) conditions, and sequence of stimulation conditions was the same across participants, with sham stimulation preceding active stimulation.
Participants by arm
| Arm | Count |
|---|---|
| Sham Doublestim, Then Anodal Doublestim Crossover design study: Participants first received 5 daily, consecutive 20 min sessions of sham Doublestim (trans-spinal direct current stimulation + peripheral direct current stimulation). After a washout period of 1 week, they then received 5 daily, consecutive 20 min sessions of anodal Doublestim (trans-spinal direct current stimulation + peripheral direct current stimulation). | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Anodal Doublestim (5 Days) | Adverse Event | 1 |
| Anodal FU (7 Days) | Lost to Follow-up | 4 |
| Baseline | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Sham Doublestim, Then Anodal Doublestim |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 26 | 0 / 24 | 1 / 24 |
| serious Total, serious adverse events | 2 / 26 | 0 / 24 | 2 / 24 |
Outcome results
Primary
Mean Percent Change From Baseline in Area Under the Curve for Objectively Measured Spastic Catch Response of the Wrist Flexors at Fast Speed
Subjects' wrists were passively extended at fast speed by a stepper motor to induce a spastic catch response, and its resistance torque was calculated in Newton meters (Nm). Mean percent change from baseline in the area under the curve for the resistance torque were compared across two timepoints (final session at day 5 and 1 week follow-up) in two conditions (sham vs. anodal Doublestim)
Time frame: baseline, final session at day 5, 1 week FU
Population: Three subjects (out of 19) were found to be significant outliers for normality testing, and were consequently removed from analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Doublestim | Mean Percent Change From Baseline in Area Under the Curve for Objectively Measured Spastic Catch Response of the Wrist Flexors at Fast Speed | Mean percent change at final session (day 5) | 13.678 percent change | Standard Error 5.537 |
| Sham Doublestim | Mean Percent Change From Baseline in Area Under the Curve for Objectively Measured Spastic Catch Response of the Wrist Flexors at Fast Speed | Mean percent change at 1 week follow-up (FU) | 15.927 percent change | Standard Error 5.537 |
| Anodal Doublestim | Mean Percent Change From Baseline in Area Under the Curve for Objectively Measured Spastic Catch Response of the Wrist Flexors at Fast Speed | Mean percent change at final session (day 5) | -8.783 percent change | Standard Error 4.911 |
| Anodal Doublestim | Mean Percent Change From Baseline in Area Under the Curve for Objectively Measured Spastic Catch Response of the Wrist Flexors at Fast Speed | Mean percent change at 1 week follow-up (FU) | -16.333 percent change | Standard Error 6.18 |
p-value: 0.004ANOVA
Secondary
Mean Modified Tardieu Scale (MTS) Score
The Modified Tardieu Scale (MTS) quantifies muscle spasticity for each joint at slow and fast velocities on a 0-5 point scale. MTS scores at fast velocity were summed across 11 joints of the upper extremity (for a total of 0-55 points), with lower scores indicating improved spasticity. Mean summed MTS scores (out of 55 total points) were compared across two timepoints (final session at day 5 and 1 week FU) in two conditions (sham vs. anodal Doublestim).
Time frame: baseline, final session at day 5, 1 week FU
Population: Three subjects (out of 19) were found to be significant outliers for normality testing, and were consequently removed from analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Doublestim | Mean Modified Tardieu Scale (MTS) Score | mean score at final session (day 5) | 23.375 scores on a scale | Standard Error 0.275 |
| Sham Doublestim | Mean Modified Tardieu Scale (MTS) Score | mean score at 1 week FU | 23.125 scores on a scale | Standard Error 0.275 |
| Anodal Doublestim | Mean Modified Tardieu Scale (MTS) Score | mean score at final session (day 5) | 21.625 scores on a scale | Standard Error 0.275 |
| Anodal Doublestim | Mean Modified Tardieu Scale (MTS) Score | mean score at 1 week FU | 21.975 scores on a scale | Standard Error 0.309 |
p-value: 0.003ANOVA