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
Phase: NA
Conditions: Essential Tremor
Sponsor: Cala Health, Inc.

EXCITE: A Pilot Study of the Cala ONE Device for Essential Tremor 
Protocol ET-13 
6 OCT 2017 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 
 
 
PROTOCOL ET-13 
6 OCT 2017 
 
 
 
 
 
 
 
 
Cala Health, Inc. 
875 Mahler Rd, Suite #168 
Burlingame, CA 94010 
 
 

3-Nov-2017

EXCITE: A Pilot Study of the Cala ONE Device for Essential Tremor 
Protocol ET-13 
6 OCT 2017 
 
 
 
CLINICAL STUDY SYNOPSIS 
Study Objective 
Title 
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 
Study Device 
Cala ONE Device 
Objective 
The study objectives are: 
- 
To evaluate the safety and initial effectiveness of the Cala ONE 
device to repeatably aid in the symptomatic relief of hand 
tremors in adults with essential tremor  
- 
To evaluate the feasibility of two different types of controls 
(sham and ‘no intervention’) and their corresponding 
endpoints for future randomized controlled trials in the home 
environment 
 
Study Design Elements 
Study Design 
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 (zero-amplitude stimulation), or ‘no intervention’, 
respectively.  Subjects randomized to the TAPS and sham arms will be 
blinded to their randomization assignments for the first 2-3 weeks of 
participation (controlled phase). After the first 2-3 weeks, all subjects 
will be crossed over to TAPS (open-label phase) for 2-3 weeks. During 
study participation, all subjects are to remain on a stable dosage of 
medications prescribed for the treatment of essential tremor, if 
applicable.   
Effectiveness 
Assessments 
The effectiveness of the Cala ONE device in reducing essential tremor 
symptoms will be evaluated by analyzing the following:  
In-office physician-rated assessments: 
- 
Clinical Rating Scale for Tremor (CRST)  
- 
Clinical Global Impression of Severity (CGI-S) 
- 
Clinical Global Impression of Improvement (CGI-I) 
Subject-rated assessments (in-office and at-home): 
- 
Bain & Findley Activities of Daily Living (ADL) Scale 
- 
Quality of life in Essential Tremor Questionnaire (QUEST) 
- 
Patient Global Impression of Severity (PGI-S) 
- 
Patient Global Impression of Improvement (PGI-I) 
- 
Subject survey of satisfaction and durability of effect (i.e. on 
average how long tremor relief lasts after a stimulation 
session) 
 

EXCITE: A Pilot Study of the Cala ONE Device for Essential Tremor 
Protocol ET-13 
6 OCT 2017 
 
 
Device-related assessments: 
- 
Motion data collected by the device during lateral postural 
holds in the home environment 
- 
Device usage metrics (e.g. number of stimulation sessions 
completed daily or changes in stimulation amplitude) 
The following measures will be evaluated between the treatment and 
sham arms during the controlled phase of the study: 
- 
In-office physician-rated assessments pre, during and post 
TAPS, compared to pre, during and post sham stimulation  
- 
In-office subject-rated assessments pre, during and post TAPS, 
compared to pre, during and post sham stimulation  
- 
At-home subject-reported assessments pre and post TAPS, 
compared to pre and post sham stimulation 
- 
Device-related assessments pre and post TAPS, compared to 
pre and post sham stimulation  
The following measures will be evaluated between the treatment and 
‘no intervention’ arms during the controlled phase of the study: 
- 
In-office physician-rated assessments post TAPS compared to 
‘no intervention’  
- 
In-office subject-rated assessments post TAPS compared to ‘no 
intervention’  
- 
At-home subject-reported assessments post TAPS compared 
to ‘no intervention’ 
The following measures will be evaluated in the open-label phase of 
the study: 
- 
In-office physician-rated assessments pre, during and post 
TAPS  
- 
In-office subject-rated assessments pre, during and post TAPS  
- 
At-home subject-reported assessments pre and post TAPS  
- 
Subject satisfaction survey 
- 
Device-related assessments 
Safety Endpoints 
The safety of the Cala ONE device will be evaluated by the incidence of 
device and therapy-related adverse events 
Number of 
Subjects 
Up to 70 subjects 
Number of Sites 
Up to five sites  
Study 
Participation 
The length of study participation is up to 6 weeks. 
Blinding 
The first 2-3 weeks of the study are double-blinded for the treatment 
and sham arms. The subjects and rating movement disorder 
neurologists will be blinded to the therapy allocation for the treatment 
and sham arms. The subjects in the ‘no intervention’ arm and their 
rating neurologists will not be blinded to their therapy allocation.   
The last 2-3 weeks are open-label, and all subjects will be given the 
option to use the Cala ONE device. 

EXCITE: A Pilot Study of the Cala ONE Device for Essential Tremor 
Protocol ET-13 
6 OCT 2017 
 
 
 
Subject Population 
Inclusion Criteria 
Prospective subjects must meet all of the following criteria to be 
eligible for study participation:  
• 
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: 
o remaining on a stable dosage of tremor and 
antidepressant medications, if applicable, during the 
duration of the study   
o no significant alcohol or caffeine consumption within 12 
hours of study visits 
o no significant alcohol or caffeine consumption within 4 
hours of twice-daily at home assessments during the 
controlled phase of the study 

EXCITE: A Pilot Study of the Cala ONE Device for Essential Tremor 
Protocol ET-13 
6 OCT 2017 
 
 
Exclusion Criteria 
Prospective subjects who meet any of the following criteria are not 
eligible for enrollment in this study:  
• 
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 
 

EXCITE: A Pilot Study of the Cala ONE Device for Essential Tremor 
Protocol ET-13 
6 OCT 2017 
 
 
Study Contacts 
Sponsor 
Cala Health, Inc.  
875 Mahler Rd, Suite #168 
Burlingame, CA 94010 
 
Contact:  Paula Chidester, MS 
Clinical Research Manager 
paula@calahealth.com 
Tel: +1 512-565-2639