Prospective Study for Symptomatic Relief of ET With Cala Therapy

• Cala TWO (Device): Wrist-worn stimulator which applies a tremor-customized stimulation pattern to an individual's nerves

Primary outcomes

• TRG (Tremor Research Group) Essential Tremor Rating Assessment Scale (TETRAS) Subset Score [Baseline to 3-months]: 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.
• Bain & Findley Activities of Daily Living (ADL) Scale Subset Score [Baseline to 3-months]: 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.

Secondary outcomes

• Kinematic Measurements, as Collected With the Device During Postural Holds, Change From Pre-stimulation to Post-stimulation Across Sessions [Average change in tremor power over 3-month study period]: 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.

Sex: All, ages: 22 Years to any

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

Participant flow

Outcome results

• TRG (Tremor Research Group) Essential Tremor Rating Assessment Scale (TETRAS) Subset Score (Primary), Mean, score on a scale: Cala TWO 12.6 +/- 2.7
• Bain & Findley Activities of Daily Living (ADL) Scale Subset Score (Primary), Mean, score on a scale: Cala TWO 18.4 +/- 3.8
• Kinematic Measurements, as Collected With the Device During Postural Holds, Change From Pre-stimulation to Post-stimulation Across Sessions (Secondary), Mean, (m/s^2)^2: Cala TWO -0.8 +/- 3.7

Adverse events

Time frame: Up to 3 months since baseline testing

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2018-06-22)
• Statistical Analysis Plan (PDF, 2019-05-22)