A Pilot Study of the Cala ONE Device for Essential Tremor (EXCITE)

A Pilot Study to Evaluate the Safety and Initial Effectiveness of the Cala ONE Device to Repeatably Aid in the Symptomatic Relief of Essential Tremor

Prospective, multi-center, randomized, controlled study designed to evaluate safety and repeatable effectiveness. Subjects will be randomized 2:1:1 to transcutaneous afferent patterned stimulation (TAPS), sham, or 'no intervention', respectively. Subjects randomized to the TAPS and sham arms will be blinded to their randomization assignments for the first two weeks of participation (controlled phase). After the first two weeks, all subjects will be crossed over to TAPS (open-label phase) for 2 weeks. During study participation, all subjects are to remain on a stable dosage of medications prescribed for the treatment of essential tremor, if applicable.

Study Overview

• Status: Completed
• Conditions: Essential Tremor
• Intervention / Treatment: Device: Cala ONE device

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94611
      • Personal Care Neurology
  • Colorado
    • Denver, Colorado, United States, 80113
      • Movement & Neuroperformance Center
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Kansas University Medical Center
  • Washington
    • Kirkland, Washington, United States, 98034
      • EvergreenHealth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be ≥22 and ≤80 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
• Postural, action or intention tremor severity score of 2 or above in the dominant hand/arm as measured by the CRST rating scale
• Significant disability due to essential tremor (Bain & Findley score of 3 or above in any one of the hand items)
• Currently or previously prescribed either propranolol or primidone for the treatment of essential tremor
• Stable dose of tremor medications for 30 days prior to study entry
• Stable dose of antidepressant medications 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 12 hours of study visits; and no significant alcohol or caffeine consumption within 4 hours of twice-daily at home assessments during the controlled phase of the study

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
• 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
• Are participating or have participated in another Cala Health clinical trial
• Significant alcohol or caffeine consumption within 12 hours of 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAPS; Subjects will receive a Cala ONE device that delivers TAPS, transcutaneous afferent patterned stimulation.	Device: Cala ONE device; The Cala ONE device is a wrist-worn stimulator which applies a tremor-customized stimulation pattern to an individual's nerves.
Sham Comparator: Sham; Subjects will receive a Cala ONE device that delivers sham stimulation.	Device: Cala ONE device; The Cala ONE device is a wrist-worn stimulator which applies a tremor-customized stimulation pattern to an individual's nerves.
No Intervention: No Intervention; Subjects will not receive a Cala ONE device, and will stay on their current treatment regimen for their essential tremor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Tremor Power	For TAPS and sham arms, subjects will be prompted to perform a lateral postural hold prior to entering their PGI-S score before and after each stimulation session. During this hold, the device will record motion data to objectively assess if there are any changes in tremor level.	Mean tremor power pre stimulation over two weeks of device usage as compared to mean tremor power post stimulation over two weeks of device usage.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Rating Scale for Tremor (CRST) After Stimulation	A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated after stimulation.	Collected before and after in-office stimulation sessions at Week 2
Change in Clinical Global Impression of Severity (CGI-S)	Tremor severity will be assessed with the 7-point CGI-S scale at baseline for all arms. For TAPS and sham arms, CGI-S will also be assessed during and after stimulation.	Collected before, during, and after in-office stimulation sessions at Week 0, Week 2, and Week 4
Clinical Global Impression of Improvement (CGI-I)	For TAPS and sham arms, the blinded rating neurologist will assess improvements in tremor level during and after stimulation.	Collected during and after in-office stimulation sessions at Week 0, Week 2, and Week 4
Change in Bain & Findley Activities of Daily Living (ADL) Scale	The complete Bain & Findley ADL questionnaire will be administered at baseline for all arms. For TAPS and sham arms, a subset of ADLs relevant to upper limb tremor will be repeated with provided props during and after stimulation. On a weekly basis, all subjects will answer the complete Bain & Findley ADL questionnaire via phone call.	Collected before, during, and after in-office stimulation sessions at Week 0, Week 2, and Week 4. Collected via phone call Week 1 and Week 3.
Subject Impression of Durability of Effect	TAPS and sham arms will also be asked how long their tremor relief lasts due to stimulation, if applicable.	Week 1, 2, 3 and 4.
Change in Quality of Life in Essential Tremor Questionnaire (QUEST)	The QUEST assessment will be administered to all subjects during in-office visits (every 2 weeks).	Week 0, 2, and 4
Change in Patient Global Impression of Severity (PGI-S)	Tremor severity will be assessed with the 7-point PGI-S scale at baseline for all arms. For TAPS and sham arms, PGI-S will also be assessed during and after stimulation during office visits. Additionally, for TAPS and sham arms, PGI-S will be entered on the device before and after each stimulation session in the home environment.	Before and after every stimulation session for TAPS and sham subjects through study completion. Twice daily for 'no intervention' subjects through study completion.
Patient Global Impression of Improvement (PGI-I)	For TAPS and sham arms, the blinded subject will assess improvements in their tremor level during and after stimulation during office visits.	Collected during and after in-office stimulation sessions at Week 0, Week 2, and Week 4
Subject Survey of Satisfaction	At the final visit, all subject will take a subject satisfaction survey which will include questions such as likelihood to recommend and other questions related to the usability of the device.	Week 4
Device Usage Metrics	For TAPS and sham arms, the device will record usage metrics such as how many times the device was used per day and stimulation amplitude, to assess if there are any changes over time within group and within subject.	Week 4
Change in Clinical Rating Scale for Tremor (CRST) After Stimulation	A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated after stimulation.	Collected before and after in-office stimulation sessions at Week 0 and 4.
Change in Clinical Rating Scale for Tremor (CRST) During Stimulation	A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated during stimulation.	Collected before and during in-office stimulation sessions at Week 0, 2 and 4.

Collaborators and Investigators

• Sponsor: Cala Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2017
• Primary Completion (Actual): March 8, 2018
• Study Completion (Actual): March 8, 2018

Study Registration Dates

• First Submitted: May 7, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2019
• Last Update Submitted That Met QC Criteria: April 8, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: ET-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data will be published, but no PHI will be made available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No