Prospective Study for Symptomatic Relief of Essential Tremor With Cala Therapy
Phase: NA
Conditions: Essential Tremor
Sponsor: Cala Health, Inc.

PROSPECT: Prospective Study for Symptomatic Relief of ET with Cala Therapy 
Protocol ET-14 
Rev A; 22JUN2018 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROSPECT: PROSPECTIVE STUDY FOR SYMPTOMATIC RELIEF OF 
ESSENTIAL TREMOR WITH CALA THERAPY 
 
 
PROTOCOL ET-14 
REV A; 22 JUNE 2018 
 
 
 
 
 
 
 
 
 
 
Cala Health, Inc. 
875 Mahler Rd, Suite #168 
Burlingame, CA 94010 
 
 
 
 

PROSPECT: Prospective Study for Symptomatic Relief of ET with Cala Therapy 
Protocol ET-14 
Rev A; 22JUN2018 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page iii of viii 
 
CLINICAL STUDY SYNOPSIS 
Study Objective 
Title 
PROSPECT: PROspective study for SymPtomatic relief of Essential 
tremor with Cala Therapy 
Study Device 
Cala TWO Device 
Objective 
The study objective is to evaluate symptomatic hand tremor relief in 
the treated hand following stimulation with the Cala TWO device in 
adults with essential tremor over a 3-month duration 
 
Study Design Elements 
Study Design 
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.  
Effectiveness 
Endpoints 
The effectiveness of the Cala TWO device in reducing essential tremor 
symptoms will be evaluated by the following:  
 
Co-Primary Effectiveness Endpoints 
• 
TRG Essential Tremor Rating Assessment Scale (TETRAS) subset 
score, relevant to the stimulated upper limb, change from pre-
stimulation at baseline to post-stimulation at 3 months. 
• 
Bain & Findley Activities of Daily Living (ADL) scale subset score, 
relevant to the stimulated upper limb, change from pre-
stimulation at baseline to post-stimulation at 3 months.  
 
Secondary Effectiveness Endpoint 
• 
Tremor power, as collected with the device during postural holds, 
change from pre-stimulation to post-stimulation across sessions.  
 
Additional Exploratory Analyses 
• 
Quality of Life in Essential Tremor Questionnaire (QUEST)  
• 
Clinician/Patient Global Impression of Severity (C/PGI-S) 
• 
Clinician/Patient Global Impression of Improvement (C/PGI-I) 
• 
Patient Session Impression of Improvement (PSI-I)  
• 
TETRAS – subset relevant to non-stimulated upper limb 
• 
TETRAS and ADL pre- versus post-stimulation within each visit 
• 
Product Survey 
• 
Device usage metrics 
Safety Endpoint 
The safety of the Cala TWO device will be evaluated by the incidence 
of device and therapy-related adverse events.  Additionally, all 
adverse events documented during study conduct will be tabulated 
and reported. 
T

PROSPECT: Prospective Study for Symptomatic Relief of ET with Cala Therapy 
Protocol ET-14 
Rev A; 22JUN2018 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page iv of viii 
 
Number of 
Subjects 
Up to 500 subjects 
Number of Sites 
Up to 40 US sites  
Study 
Participation 
The length of study participation is 3 months +/- 2 weeks 
Follow-up 
Schedule 
Enrolled subjects will return to the site at 1 month +/- 1 week and 3 
months +/- 2 weeks from enrollment 
 
Subject Population 
Inclusion Criteria 
Prospective subjects must meet all of the following criteria to be 
eligible for study participation:  
• 
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: 
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 8 
hours prior to study visits 
o no usage of the Cala TWO device within 8 hours prior to 
study visits 
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) 

PROSPECT: Prospective Study for Symptomatic Relief of ET with Cala Therapy 
Protocol ET-14 
Rev A; 22JUN2018 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page v of viii 
 
• 
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 
 
 
 
 
 
 

PROSPECT: Prospective Study for Symptomatic Relief of ET with Cala Therapy 
Protocol ET-14 
Rev A; 22JUN2018 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page vi of viii 
 
Study Contacts 
Sponsor 
Cala Health, Inc.  
875 Mahler Rd, Suite #168 
Burlingame, CA 94010 
 
Contact:  Paula Chidester, MS 
Clinical Program Manager 
paula@calahealth.com 
Tel: +1 512-565-2639