Essential Tremor
Conditions
Brief summary
The purpose of this study is evaluate the effectiveness and safety of a possible new treatment for Essential Tremor (ET) using external wearable sensors, which have the capability of recording acceleration and Electromyography (EMG). This therapy is called Responsive Deep Brain Stimulation (R-DBS). R-DBS systems will communicate with a computer, and apply stimulation when the computer detects patterns associated with tremor. This detection will suppress pathological activity and improve or alleviate the tremor. Currently, DBS is approved for the treatment of ET; however, stimulation is delivered continuously even when tremor or other symptoms are absent. Continuous DBS can lead to unwanted side effects such as stuttering and gait\\balance problems. On the other hand, R-DBS will turn on only if activity associated with ET from the external sensors is detected.
Detailed description
The overall purpose of this application is to capture pathological activity related to essential tremor using external wearable sensors to responsively initiate or terminate DBS. To this end, the researchers propose to use the Nexus-D system, which requires a firm ware update to an Activa Implantable Neurostimulator (INS), and it will in a smart way turn DBS on/off in patients. The study team will recruit subjects with Activa SC or PC neurostimulator implants during 6 post-operative programming visits. The research group is already familiar with and is in possession of the Nexus-D system, and the investigators have successfully performed responsive DBS in two patients with Tourette syndrome (TS) and in four patients with Parkinson's disease in acute settings. The lab is also equipped with wireless wearable sensor and amplifier systems, such as a 16-unit wireless EMG+ acceleration+inertia Trigno Wireless Bio Acquisition System (Delsys Inc, Natick, MA). The study team aims to combine these signal modalities to capture pathological symptoms and generate commands to initiate or terminate DBS (also record adverse side effects, if any). The project goal is to characterize the clinical efficacy, side effect profile, and battery life of closed-loop DBS in acute settings using wearable sensors in essential tremor patients.
Interventions
DEVICEResponsive deep brain stimulation
Responsive deep brain stimulation (R-DBS) therapy will be delivered responsively based on the level of their symptoms as detected by wearable EMG and inertia (acceleration) sensors.
Sponsors
Medtronic
De Luca Foundation
National Institute of Neurological Disorders and Stroke (NINDS)
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Provide informed consent * Patient is over 21 years of age * Patient has had a significant disabling, medication-refractory upper extremity tremor with no evidence of non-ET central nervous system disease or injury for at least three (3) months prior to implantation of Activa SC, PC, or RC device. * Patient receives Vim electrode and Activa SC, PC or RC device implants, and recovers fully after surgery. * Patient is available for study participation after their clinical programming appointments for six months.
Exclusion criteria
* Medication related movement disorders. * Any suspicion of Parkinsonian tremor, including presence of Parkinsonian features such as bradykinesia, rigidity, or postural instability. * Severe medical co-morbidity including cardiovascular disorder, lung disorder, kidney disease, continuous neurological disease, hematological disease, or frailty that impact tolerability of the surgery as judged by the screening physicians. * Patient is undergoing a lead revision surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Rating Scale for Tremor (CRST) | 30 minutes during one monthly visit after clinical continuous deep brain stimulation is optimized. | Responsive deep brain stimulation as an effective alternative to continuous deep brain stimulation. Clinical Tremor Rating Scale (TRS), rated by a blinded neurologist, during responsive brain stimulation will be compared to scores during continuous deep brain stimulation and no stimulation. The minimum and maximum score range for this scale is 0-80, with higher score indicating worse outcome. |
Countries
United States
Participant flow
Recruitment details
17 patients were enrolled into the single arm study. 5 patients withdrew from the study. We are comparing their clinical Tremor Rating Scores (TRS) for three conditions: deep brain stimulation (DBS) OFF, standard (continuous) DBS, and responsive DBS (the trial condition).
Participants by arm
| Arm | Count |
|---|---|
| Subjects With Essential Tremor This cohort will receive deep brain stimulation (DBS) therapy responsively based on the level of their symptoms as detected by wearable EMG and inertia (acceleration) sensors.
Responsive deep brain stimulation: Responsive deep brain stimulation (R-DBS) therapy will be delivered responsively based on the level of their symptoms as detected by wearable EMG and inertia (acceleration) sensors.
The clinical tremor rating scale (TRS) with R-DBS will be compare to no DBS and continuous DBS TRS scores. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Subjects With Essential Tremor |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 74.2 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 17 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Clinical Rating Scale for Tremor (CRST)
Responsive deep brain stimulation as an effective alternative to continuous deep brain stimulation. Clinical Tremor Rating Scale (TRS), rated by a blinded neurologist, during responsive brain stimulation will be compared to scores during continuous deep brain stimulation and no stimulation. The minimum and maximum score range for this scale is 0-80, with higher score indicating worse outcome.
Time frame: 30 minutes during one monthly visit after clinical continuous deep brain stimulation is optimized.
Population: We statistically compared the Tremor Rating Scale (TRS) scores for responsive deep brain stimulation (R-DBS) to standard continuous DBS (cDBS) and to NO DBS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects With Essential Tremor | Clinical Rating Scale for Tremor (CRST) | DBS Off | 18.39534884 score on a scale | Standard Deviation 9.191454455 |
| Subjects With Essential Tremor | Clinical Rating Scale for Tremor (CRST) | Continuous DBS | 13.97674419 score on a scale | Standard Deviation 5.616677429 |
| Subjects With Essential Tremor | Clinical Rating Scale for Tremor (CRST) | Responsive DBS | 14.58139535 score on a scale | Standard Deviation 5.197217929 |
Comparison: TRS scores measured across different stimulation conditions were assessed using a mixed model ANOVA with the participant as a random effect. All post-hoc comparisons were Bonferroni corrected.p-value: <0.01ANOVA