Prospective Study for Symptomatic Relief of ET With Cala Therapy

Study Overview
=================
Brief Summary
-----------------
Prospective, multi-center, single-arm, non-significant risk study designed to evaluate the Cala TWO device. Subjects will be screened for eligibility and fitted with a Cala TWO device. Subjects will wear the device at home for a period of 3 months, during which they will be asked to stimulate their dominant hand twice a day. The stimulation amplitude will be based on each subject's stimulation threshold. Subjects will have in clinic assessments at enrollment, month 1 and 3.

Official Title
-----------------
Prospective Study for Symptomatic Relief of Essential Tremor With Cala Therapy

Conditions
-----------------
Essential Tremor

Intervention / Treatment
-----------------
* Device: Cala TWO


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be ≥22 years of age Competent and willing to provide written, informed consent to participate in the study A diagnosis of essential tremor as confirmed from clinical history and examination by a movement disorder neurologist A tremor severity score of 2 or above in the dominant hand/arm as measured by any one of the TETRAS upper limb items and a minimum subset score of 6 across all upper limb items Significant disability due to essential tremor (Bain & Findley score of 3 or above in any one of the upper limb items and a minimum subset score of 8 across all upper limb items) Stable dose of tremor medications, if applicable, for 30 days prior to study entry Stable dose of antidepressant medications, if applicable, for 90 days prior to study entry Willing to comply with study protocol requirements including: remaining on a stable dosage of tremor and antidepressant medications, if applicable, during the duration of the study no significant alcohol or caffeine consumption within 8 hours prior to study visits no usage of the Cala TWO device within 8 hours prior to study visits Exclusion Criteria: Moderate to severe ethanol dependence as defined by the criteria outlined in the DSM-5 (score of 4 or higher) Implanted electrical medical device, such as a pacemaker, defibrillator, or deep brain stimulator, or implanted metal in the wrist to be stimulated Previous thalamotomy procedure, including stereotactic thalamotomy, gamma knife radiosurgical thalamotomy, and focused ultrasound for the treatment of tremor Suspected or diagnosed epilepsy or other seizure disorder Swollen, infected, inflamed areas, or skin eruptions, open wounds, or cancerous lesions of skin at stimulation site Peripheral neuropathy affecting the tested upper extremity Presence of any other neurodegenerative disease like Parkinson-plus syndromes suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease. Anyone suspected to have the diagnosis of idiopathic Parkinson's disease (PD). This includes excluding anyone with the presence of parkinsonian features including bradykinesia rigidity, or postural instability. Subjects who exhibit only mild resting tremor but no other symptoms or signs of PD may be included. Botulinum toxin injection for hand tremor within 6 months prior to study enrollment Are participating or have participated in another interventional clinical trial in the last 30 days which may confound the results of this study, unless approved by the Sponsor Significant alcohol or caffeine consumption within 8 hours prior to study enrollment, which may confound the results of the study, where significant caffeine is considered more than 95 mg (equivalent to a cup of coffee), and significant alcohol is considered more than 14 g (equivalent to 5 oz of wine, 12 oz of beer, or 1.5 oz of distilled spirits). Subjects unable to communicate with the investigator and staff Any health condition that in the investigator's opinion should preclude participation in this study Pregnancy or anticipated pregnancy during the course of the study

Ages Eligible for Study
-----------------
Minimum Age: 22 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cala TWO<br>Two 40-minute stimulation sessions daily, separated by at least two hours | Device: Cala TWO<br>* Wrist-worn stimulator which applies a tremor-customized stimulation pattern to an individual's nerves<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TRG (Tremor Research Group) Essential Tremor Rating Assessment Scale (TETRAS) Subset Score | Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) subset score: TETRAS subset score relevant to the stimulated upper limb. The subset score is the sum of 6 rated tasks. Each task is rated 0 to 4, where a higher score indicates more severe tremor. Minimum subset score = 0; Maximum subset score = 24. | Baseline to 3-months | 
| Bain & Findley Activities of Daily Living (ADL) Scale Subset Score | Bain & Findley ADL subset score relevant to the stimulated upper limb. The subset score is the sum of 8 rated tasks. Each task is rated 1 to 4, where a higher score indicates more severe tremor. Minimum subset score = 8; Maximum subset score = 32. | Baseline to 3-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinematic Measurements, as Collected With the Device During Postural Holds, Change From Pre-stimulation to Post-stimulation Across Sessions | Subjects will be prompted to perform a postural hold task before and after each stimulation session. During this task, the device will record kinematic data using on-board motion sensors to objectively assess if there are any changes in tremor level. The change in each patient's pre- and post-stimulation tremor power was defined as the median change over all valid stimulation sessions. Sample mean and standard deviations were computed using the median change value from all patients. | Average change in tremor power over 3-month study period |