Stroke, Cerebrovascular Accident (CVA), Hemiparesis
Conditions
Keywords
Transcutaneous vagus nerve stimulation (tVNS), VNS, robotic therapy, occupational therapy, motor rehabilitation
Brief summary
The purpose of this study is to evaluate if multiple therapy sessions of Transcutaneous Vagus Nerve Stimulation (tVNS) combined with robotic arm therapy lead to a greater functional recovery in upper limb mobility after stroke than that provided by robotic arm therapy in a sham stimulation condition.
Detailed description
Promising new animal research suggests that vagus nerve stimulation paired with motor intervention induces movement-specific plasticity in the motor cortex and improves limb function after stroke. These results were recently extended to the first clinical trial, in which patients with stroke demonstrated significant improvements in upper limb function following rehabilitation paired with implanted VNS. Currently, vagus nerve stimulation is being used clinically to treat a number of human diseases including migraine headaches, epilepsy, and depression, and these investigations are expanding to deliver stimulation via a transcutaneous route to potentially improve intervention efficacy and decrease side effects. This pilot study will combine non-invasive transcutaneous stimulation of the vagus nerve with upper limb robotic therapy to investigate the potential of tVNS to augment improvements gained with robotic therapy in patients with chronic hemiparesis after stroke.
Interventions
tVNS is a non-invasive form of vagus nerve stimulation, activating the auricular branch of the vagus nerve transcutaneously through the cymba concha at the pinna of the ear.
DEVICESham Transcutaneous Vagus Nerve Stimulation (tVNS)
tVNS is a non-invasive form of vagus nerve stimulation, activating the auricular branch of the vagus nerve transcutaneously through the cymba concha at the pinna of the ear. Sham tVNS means the patient is wearing the device, but it is turned off and not delivering current during the treatment. This is a placebo condition, which is used as a study control.
Sponsors
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Both the participants and investigators performing and analyzing clinical and objective outcome measures will remain blind to condition. Participants will be told that they have a 50-50 chance of receiving either active or sham stimulation, but they will not be told which condition they receive.
Intervention model description
This is a double-blind, sham controlled treatment study in which patients will have a 50/50 chance of receiving robotic arm therapy with either active transcutaneous vagus nerve stimulation (tVNS) or sham tVNS (placebo).
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Individuals between 18 and 85 years of age * First single focal unilateral supratentorial ischemic stroke with diagnosis verified by brain imaging (MRI or CT scans) that occurred at least 6 months prior * Cognitive function sufficient to understand the experiments and follow instructions (per interview with Speech Pathologist or PI) * Fugl-Meyer assessment 12 to 44 out of 66 (neither hemiplegic nor fully recovered motor function in the muscles of the shoulder, elbow, and wrist).
Exclusion criteria
* Botox treatment within 3 months of enrollment * Fixed contraction deformity in the affected limb * Complete and total flaccid paralysis of all shoulder and elbow motor performance * Prior injury to the vagus nerve * Severe dysphagia * Introduction of any new rehabilitation interventions during study * Individuals with scar tissue, broken skin, or irremovable metal piercings that may interfere with the stimulation or the stimulation device * Highly conductive metal in any part of the body, including metal injury to the eye; this will be reviewed on a case by case basis for PI to make a determination * Pregnant or plan on becoming pregnant or breastfeeding during the study period * Significant arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, sick sinus syndrome, and A-V blocks (enrollment to be determined by PI review) * Presence of an electrically, magnetically or mechanically activated implant (including cardiac pacemaker), an intracerebral vascular clip, or any other electrically sensitive support system; Loop recorders will be reviewed on a case by case basis by PI and the treating Cardiologist to make a determination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | baseline, discharge at 3 weeks (immediately following the intervention), and follow-up at 16 weeks (3 months after the intervention) | The median absolute change in surface electromyographic (sEMG) peak amplitude of the bicep/tricep during gravity-eliminated, unassisted extensor movements was calculated from baseline to discharge at 3 weeks (immediately following the intervention) and again at 16 weeks (3 months follow-up from the intervention) in each training condition (sham tVNS + robotic arm training vs. active tVNS + robotic arm training). Bicep and tricep peak sEMG amplitude scores were calculated as a percentage of the maximal volitional contraction (MVC), with larger values indicating a greater absolute change (negative or positive) in bicep/tricep peak muscle activity during extensor movements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score | baseline, discharge at 3 weeks (immediately following the intervention), and follow-up at 16 weeks (3 months after the intervention) | The median change in Upper Extremity Fugl-Meyer Score will be calculated from baseline to discharge at 3 weeks (immediately following the intervention) and again at 16 weeks (3 months follow-up from the intervention) in each training condition (sham tVNS + robotic arm training vs. active tVNS + robotic arm training). The median change in Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active tVNS + Robotic Arm Therapy Transcutaneous Vagus Nerve Stimulation (tVNS) will be delivered non-invasively via the ear (targeting the auricular branch of the vagus nerve) during robotic arm therapy sessions lasting \
60 minutes, 3x per week for 3 weeks.
Transcutaneous Vagus Nerve Stimulation (tVNS): tVNS is a non-invasive form of vagus nerve stimulation, activating the auricular branch of the vagus nerve transcutaneously through the cymba concha at the pinna of the ear. | 18 |
| Sham tVNS + Robotic Arm Therapy Sham (placebo) transcutaneous Vagus Nerve Stimulation (tVNS) will be delivered non-invasively via the ear (targeting the auricular branch of the vagus nerve) during robotic arm therapy sessions lasting \
60 minutes, 3x per week for 3 weeks.
Sham Transcutaneous Vagus Nerve Stimulation (tVNS): tVNS is a non-invasive form of vagus nerve stimulation, activating the auricular branch of the vagus nerve transcutaneously through the cymba concha at the pinna of the ear. Sham tVNS means the patient is wearing the device, but it is turned off and not delivering current during the treatment. This is a placebo condition, which is used as a study control. | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | study temporary closure due to covid-19 pandemic | 1 | 1 |
Baseline characteristics
| Characteristic | Active tVNS + Robotic Arm Therapy | Total | Sham tVNS + Robotic Arm Therapy |
|---|---|---|---|
| Age, Continuous | 56.0 years | 59.0 years | 62.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 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 | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 7 Participants | 17 Participants | 10 Participants |
| Region of Enrollment United States | 18 Participants | 36 Participants | 18 Participants |
| Sex: Female, Male Female | 9 Participants | 18 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 18 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 0 / 18 | 2 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep
The median absolute change in surface electromyographic (sEMG) peak amplitude of the bicep/tricep during gravity-eliminated, unassisted extensor movements was calculated from baseline to discharge at 3 weeks (immediately following the intervention) and again at 16 weeks (3 months follow-up from the intervention) in each training condition (sham tVNS + robotic arm training vs. active tVNS + robotic arm training). Bicep and tricep peak sEMG amplitude scores were calculated as a percentage of the maximal volitional contraction (MVC), with larger values indicating a greater absolute change (negative or positive) in bicep/tricep peak muscle activity during extensor movements.
Time frame: baseline, discharge at 3 weeks (immediately following the intervention), and follow-up at 16 weeks (3 months after the intervention)
Population: 30 patients completed 9 sessions (3x/week for 3 weeks) of robotic arm training + sham or active tVNS, and 3 month follow-up at 16 weeks. One patient in the sham condition had corrupted sEMG measures, so 29 participants were consequently included in the efficacy analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in bicep peak amplitude from baseline to 3 month follow-up | 21.730 percentage of MVC |
| Active tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in bicep peak amplitude from baseline to discharge after 3 weeks of training | 22.310 percentage of MVC |
| Active tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in tricep peak amplitude from baseline to 3 month follow-up | 10.520 percentage of MVC |
| Active tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in tricep peak amplitude from baseline to discharge after 3 weeks of training | 16.070 percentage of MVC |
| Sham tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in tricep peak amplitude from baseline to 3 month follow-up | 11.455 percentage of MVC |
| Sham tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in tricep peak amplitude from baseline to discharge after 3 weeks of training | 10.055 percentage of MVC |
| Sham tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in bicep peak amplitude from baseline to discharge after 3 weeks of training | 7.010 percentage of MVC |
| Sham tVNS + Robotic Arm Therapy | Median Absolute Change From Baseline in Electromyographic (EMG) Peak Amplitude of the Bicep/Tricep | Median absolute change in bicep peak amplitude from baseline to 3 month follow-up | 13.545 percentage of MVC |
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.445Wilcoxon (Mann-Whitney)
p-value: 0.678Wilcoxon (Mann-Whitney)
p-value: 0.777Wilcoxon (Mann-Whitney)
Secondary
Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score
The median change in Upper Extremity Fugl-Meyer Score will be calculated from baseline to discharge at 3 weeks (immediately following the intervention) and again at 16 weeks (3 months follow-up from the intervention) in each training condition (sham tVNS + robotic arm training vs. active tVNS + robotic arm training). The median change in Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.
Time frame: baseline, discharge at 3 weeks (immediately following the intervention), and follow-up at 16 weeks (3 months after the intervention)
Population: 30 patients completed 9 sessions (3x/week for 3 weeks) of robotic arm training + sham or active tVNS, and 3 month follow-up at 16 weeks. A total of 30 participants were consequently included in the efficacy analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tVNS + Robotic Arm Therapy | Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score | Median change from baseline to discharge at 3 weeks | 2.000 scores on a scale |
| Active tVNS + Robotic Arm Therapy | Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score | Median change from baseline to 3 month follow-up | 2.330 scores on a scale |
| Sham tVNS + Robotic Arm Therapy | Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score | Median change from baseline to 3 month follow-up | 1.670 scores on a scale |
| Sham tVNS + Robotic Arm Therapy | Median Change From Baseline in Upper Extremity Fugl Meyer Assessment Score | Median change from baseline to discharge at 3 weeks | 2.500 scores on a scale |
p-value: 1Wilcoxon (Mann-Whitney)
p-value: 0.95Wilcoxon (Mann-Whitney)