A Study of Safety and Efficacy of Transcutaneous Afferent Patterned Stimulation (TAPS) for Reduction of Action Tremor in Parkinson's Disease (PD)
Phase: NA
Conditions: Parkinson Disease
Sponsor: Cala Health, Inc.

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A STUDY OF SAFETY AND EFFICACY OF TRANSCUTANEOUS AFFERENT PATTERNED STIMULATION 
(TAPS) FOR REDUCTION OF ACTION TREMOR IN PARKINSON’S DISEASE (PD) 
 
PROTOCOL PD-02 
1-0CT-2020 
REV A 
 
 
 
 
 
 
 
 
Cala Health, Inc. 
875 Mahler Rd, Suite #168 
Burlingame, CA 94010 
 
 
 
 
 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation (TAPS) 
for reduction of action tremor in Parkinson’s Disease (PD) 
PD-02 
SPONSOR SIGNATURE PAGE 
Prepared by: 
Ruta Deshpande 
Date 
Approved by: 
Clinical Affairs 
Vivien Zraick 
Date 
Regulatory Affairs 
Janeece Richards 
Date 
27-OCT-2020
28-OCT-2020
10/28/2020

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page i of vii 
 
 
CLINICAL STUDY SYNOPSIS 
Study Objective 
Title 
A study of safety and efficacy of Transcutaneous Afferent Patterned 
Stimulation (TAPS) for reduction of action tremor in Parkinson’s 
Disease (PD) 
Study Device 
Cala Trio 
Objective 
Demonstrate safety and efficacy of TAPS delivered by the Cala Trio™ 
device as a treatment for action tremor in subjects with Parkinson’s 
disease hand tremor. 
 
Study Design Elements 
Study Design  
Single arm study 
Overview of 
Study Visits and 
Procedures 
This study will include both subjects on levodopa and subjects taking 
other Parkinson’s medications/unmedicated for Parkinson’s.  Subjects 
will be screened for eligibility and fitted with a Cala Trio device. Due to 
COVID-19 social distancing requirements, visits requiring physician or 
subject rated assessments will be conducted via telemedicine (i.e., 
video call). During Visit 1 (Day -7), enrollment will consist of subject 
eligibility/screening using clinician rated UPDRS assessments. During 
Visit 2a (Day -1), subjects will receive device training and calibration 
instructions. During Visit 2b (Day 0), UPDRS assessments and ability 
to conduct ADLs will be assessed pre and post stimulation session. 
Visits 2a and 2b may be combined into a single visit. Subjects will use 
Cala Trio at home for a period of 4 weeks (Day 1- Day 28). During Visit 
3 (Day 28), the subjects will exit the study after a UPDRS and ADLs 
assessment pre and post stimulation session. 
Efficacy 
Assessments 
• 
Primary: Within subject comparison of tremor power before 
stimulation to after stimulation in dominant arm 
• 
Secondary: Within subject comparison of ADLs and UPDRS across 
Visits 1-3 
Safety  
The safety of the peripheral nerve stimulation will be characterized by 
the incidence of device and therapy-related adverse events 
Number of 
Subjects 
Up to 60 subjects 
Number of Sites 
1 site  
Study 
Participation 
The length of study participation is up to 6 weeks 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page ii of vii 
 
 
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 
• 
Clinically significant postural tremor as defined by: 
o Dominant hand/arm exhibiting postural tremor ≥ 2 
(while in the off state) as assessed by the MDS-UPDRS 
postural tremor score 
• 
Stable dose of Parkinson’s disease medications, if applicable, for 
30 days prior to study entry 
• 
Willing to comply with study protocol requirements including: 
o Having the ability to do telemedicine or video calls for 
study visits  
o remaining on a stable dosage of Parkinson’s medications, 
if applicable, during the duration of the study 
o no significant caffeine consumption within 8 hours of 
study visits 
Exclusion Criteria 
Prospective subjects who meet any of the following criteria are not 
eligible for enrollment in this study: 
 
• 
Implanted electrical medical device, such as a pacemaker, 
defibrillator, or deep brain stimulator 
• 
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 or dementia. 
These may include: multisystem atrophy, progressive 
supranuclear palsy, dementia with Lewy bodies, and Alzheimer’s 
disease. 
• 
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 caffeine consumption within 8 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). 
• 
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 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page iii of vii 
 
 
Study Contacts 
Sponsor 
Cala Health, Inc.  
875 Mahler Rd, Suite #168 
Burlingame, CA 94010 
 
Contact:  
Vivien Zraick  
Director of Clinical Operations 
vivien@calahealth.com 
415-786-6848 
 
 
 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page iv of vii 
 
Table of Contents 
1.0 
Introduction ...................................................................................................................................... 1 
1.1 
Scientific Background ................................................................................................................................... 1 
2.0 
Device Description .......................................................................................................................... 2 
2.1 
Intended Use .................................................................................................................................................... 2 
2.2 
Instruction for Use and Labeling ............................................................................................................. 3 
3.0 
Study Design ...................................................................................................................................... 4 
3.1 
Overview ............................................................................................................................................................ 4 
3.2 
Study Objectives ............................................................................................................................................. 4 
3.3 
Inclusion Criteria ............................................................................................................................................ 4 
3.4 
Exclusion Criteria ........................................................................................................................................... 4 
3.5 
Study Assessments ........................................................................................................................................ 5 
3.6 
Safety ................................................................................................................................................................... 5 
3.7 
Blinding .............................................................................................................................................................. 5 
3.8 
Sample Size ....................................................................................................................................................... 5 
3.9 
Study Design Schematic ............................................................................................................................... 6 
3.10 
Subject Recruitment ...................................................................................................................................... 6 
3.11 
Pre-Screening/Scheduling ......................................................................................................................... 6 
3.12 
Informed Consent ........................................................................................................................................... 6 
3.13 
Screening ........................................................................................................................................................... 6 
3.14 
Enrollment ........................................................................................................................................................ 7 
3.15 
Visit 1 ................................................................................................................................................................... 7 
3.16 
Visit 2 ................................................................................................................................................................... 7 
3.17 
Home-Usage ...................................................................................................................................................... 8 
3.18 
Visit 3/Study exit ............................................................................................................................................ 9 
3.19 
Subjects Compensation ............................................................................................................................. 10 
4.0 
Schedule of Assessments ............................................................................................................ 10 
5.0 
Risk and Benefit Assessment ..................................................................................................... 11 
5.1 
Justification for the Study ........................................................................................................................ 11 
5.2 
Description and Analysis of All Potential Risks to Subjects ...................................................... 11 
5.3 
Potential Benefits ........................................................................................................................................ 13 
5.4 
Alternatives for Participation ................................................................................................................ 13 
6.0 
Clinical Event Definitions and Reporting .............................................................................. 13 
6.1 
Definitions ...................................................................................................................................................... 13 
6.2 
Adverse Event Reporting ......................................................................................................................... 13 
6.3 
Device Observations and Malfunctions ............................................................................................. 14 
7.0 
Data Quality Assurance ............................................................................................................... 14 
7.1 
Data Collection and Storage .................................................................................................................... 14 
8.0 
Site Training .................................................................................................................................... 15 
8.1 
Protocol Deviations .................................................................................................................................... 15 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc. 
Page v of vii 
 
9.0 
Statistical Methods ........................................................................................................................ 15 
9.1 
General Principles ....................................................................................................................................... 15 
9.2 
Safety Endpoint Analysis ......................................................................................................................... 15 
9.3 
Primary Effectiveness Endpoints Analyses ..................................................................................... 15 
9.4 
Secondary Effectiveness Endpoint Analysis .................................................................................... 16 
9.5 
Additional Exploratory Effectiveness Analyses ............................................................................. 16 
9.6 
Planned Analyses ........................................................................................................................................ 16 
9.7 
Sample Size and Power ............................................................................................................................. 17 
10.0 
Study Administration ............................................................................................................... 17 
10.1 
Institutional Review Board Approval ................................................................................................. 17 
10.2 
Amending the Protocol ............................................................................................................................. 17 
10.3 
Privacy and Confidentiality ..................................................................................................................... 18 
10.4 
Record Retention ......................................................................................................................................... 18 
10.5 
Device Accountability ................................................................................................................................ 18 
10.6 
Sponsor Responsibilities .......................................................................................................................... 18 
10.7 
Investigator Responsibilities .................................................................................................................. 18 
11.0 
Publication .................................................................................................................................. 19 
12.0 
References ................................................................................................................................... 20 
13.0 
Revision History ........................................................................................................................ 21 
 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 1 of 24 
 
 
1.0 Introduction 
Idiopathic Parkinson’s disease (PD) is characterized by the cardinal motor signs and 
symptoms of rest tremor, bradykinesia and muscle rigidity. The perception of most PD 
clinicians is that of these, bradykinesia is the most disabling symptom in early and moderate 
PD (balance/gait difficulties and cognitive impairment are almost universally agreed to be 
the most disabling feature in more advanced PD). The classic teaching of treatment for PD 
tremor is that because it is predominant at “rest” and often resolves with movement and 
when reaching for a target, it is not functionally very disabling and therefore should not be a 
focus of therapeutic outcomes. However, for a substantial number of people with PD, the 
postural and kinetic components of their tremor are indeed disabling.    
Further, of all of the cardinal motor features of PD, tremor is the most resistant in response 
to dopaminergic therapies [1-2]. For many with disabling PD tremor, the only effective 
therapeutic alternative is Deep Brain Stimulation (DBS), which is a highly invasive 
procedure. 
The Cala Trio device may offer patients with PD a novel non-pharmacological, non-invasive 
alternative, in the form of stimulation of peripheral nerves, to aid in action hand tremor 
relief. This highly innovative form of therapy will have important health, quality of life, and 
economic benefits for PD patients.   
1.1 
Scientific Background 
Transcutaneous electrical nerve stimulation (TENS) is a form of noninvasive stimulation of 
peripheral nerves that has been shown to be safe and effective in treating various pain 
syndromes [3-6].  The mechanism of TENS is thought to be modulation of sensory input at 
the level of the spinal cord or brain.  
Traditional TENS and DBS use continuous, fixed-frequency stimulation; however, 
accumulating evidence suggests that patterned electrical stimulation may improve the 
therapies’ selectivity and effectiveness [7-10].   There is also specific evidence supporting 
the use of an alternating stimulation pattern for tremor reduction [11]. Peripheral nerve 
stimulation at the wrist activates neural networks similar to those responsible for the 
therapeutic mechanism of DBS in suppressing tremor [12-13]. Furthermore, recent 
literature suggests that the timing of stimulation in relation to the tremor is critical for 
effective tremor suppression [14-15]. 
Based on this research, Cala Health developed the Cala Trio device, which delivers 
alternating bursts of transcutaneous electrical stimulation to the radial and median nerves 
at the wrist.  The stimulation is tremor-customized, meaning that each nerve receives bursts 
of stimulation at the patient’s measured tremor frequency. This new form of non-invasive 
peripheral nerve stimulation is called transcutaneous afferent patterned stimulation 
(TAPS).  TAPS is designed specifically to relieve hand tremor symptoms in patients with 
essential tremor (ET). The purpose of this study is to demonstrate the safety and efficacy of 
TAPS’ utility in the new indication of PD.  
 
 
 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 2 of 24 
 
 
2.0 Device Description 
2.1 
Intended Use 
The Cala Trio device (Figure 1) is an investigational device designed for the delivery of 
Transcutaneous Afferent Peripheral Stimulation (TAPS). The device is to be used only in 
accordance with the approved investigational plan and requires informed consent. 
2.1.1 
Cala Trio Device 
The Cala Trio device is designed to deliver TAPS to the median and radial nerves of the wrist 
on which it is worn. The device system includes three components listed below; details 
about these components follow. 
Stimulator – a body worn stimulator which snaps into a wristband to apply a customized 
stimulation pattern to the median and radial nerves of an individual; 
Band – a wristband with embedded multi-use electrodes which conduct the stimulation. 
Unlike standard hydrogel electrodes, the multi-use electrodes are not limited to single use 
and may be repeatedly used by the same subject; 
Base station – a charging base station which charges the device and may upload device data 
to a secure cloud platform. 
 
 
 
 
 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 3 of 24 
 
 
2.1.2 
Stimulator 
The stimulator contains the electronics for providing TAPS and was designed with careful 
considerations of use by subjects with hand tremors. There are 3 easy-to-press buttons 
(Figure 1) on the stimulator that are used for calibration and stimulation amplitude 
adjustment, among other functions. Text prompts, stimulation delivery parameters, and 
other messages are provided on a full color display to provide instructions and stimulation 
delivery information to the clinician and subject throughout device use. A countdown timer 
automatically terminates the delivery of stimulation after a 40-minute treatment session. 
The stimulator is powered by a rechargeable battery, which can be recharged through the 
base station (see additional details below). The stimulator produces charge-balanced, 
current-controlled, biphasic, square waveforms. The duration of the primary (depolarizing) 
phase is 300 μsec, the frequency is 150 Hz, and the maximum current is 8 mA. The current is 
delivered to alternating electrode pairs in the band that target the median and radial nerves 
of the subject. The stimulation alternates between electrode pairs at the subject’s tremor 
frequency (4 – 12 Hz), which is measured during a calibration procedure while the subject 
performs a tremor-inducing task. The tremor frequency is measured by motion sensors 
contained within the stimulator which gather kinematic data. 
2.1.3 
Band 
Bands are constructed from a microfiber material with connectors to interface with the 
stimulator and a Velcro fastener to comfortably secure the device to the subject’s wrist, 
much like a wristwatch. 
There are multiuse electrodes are embedded in the band. The electrodes allow for good 
electrical conduction to the subject’s skin. Unlike standard hydrogel electrodes, the 
electrodes are not limited to single use and may be repeatably used by the same subject for 
up to 90 consecutive days. 
The electrodes are spaced at appropriate intervals around the circumference of the band in 
order to target the median and radial nerves properly. To accommodate a broad 
distribution of wrist sizes, the band has three sizes (small, medium, and large). The band is 
also right or left-handed to target the appropriate nerves of the prescribed hand with 
tremor. 
2.1.4 
Base Station 
The base station is supplied with the Cala Trio device. For safety considerations, the Cala 
Trio device is designed such that it cannot be mechanically connected to the base station 
when it is worn by a subject (e.g., during stimulation delivery). The Cala Trio device is 
charged through the base station, which may be connected to a secure cloud platform which 
stores device data (e.g. kinematic data and usage information). 
2.2 
Instruction for Use and Labeling  
The Cala Trio device will be used in accordance with its instructions for use. 
The labeling on the Cala Trio device includes the statement, "CAUTION:  Investigational 
Device.  Limited by United States law to investigational use", as required by United States 
federal regulations. 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 4 of 24 
 
 
3.0 Study Design 
3.1 
Overview 
This is a single arm study done involving telemedicine visits and a home use period. 
Subjects will be seen for up to 4 telemedicine visits and will have a 4 week treatment period 
at home. During the treatment period, subjects will be asked to stimulate their dominant 
hand at home 2 times per day, preferably at the same time every day, measuring kinematics 
before and after every therapy session.  
This study will include both subjects on levodopa and subjects taking other Parkinson’s 
medications/unmedicated for Parkinson’s.  
3.2 
Study Objectives 
The study objective is to demonstrate safety and efficacy of TAPS delivered by the Cala 
Trio™ device as a treatment for action hand tremor in subjects with Parkinson’s disease. 
3.3 
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 
• 
Clinically significant postural tremor as defined by: 
o Dominant hand/arm exhibiting postural tremor ≥ 2 (while in the off state) as 
assessed by the MDS-UPDRS postural tremor score 
• 
Stable dose of Parkinson’s disease medications, if applicable, for 30 days prior to study 
entry 
• 
Willing to comply with study protocol requirements including: 
o remaining on a stable dosage of Parkinson’s medications, if applicable, during 
the duration of the study 
o no significant caffeine consumption within 8 hours of study visits 
o Having the ability to do telemedicine or video calls for study visits  
3.4 
Exclusion Criteria 
Prospective subjects who meet any of the following criteria are not eligible for enrollment in 
this study: 
• 
Implanted electrical medical device, such as a pacemaker, defibrillator, or deep brain 
stimulator 
• 
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 or dementia. These may include: 
multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and 
Alzheimer’s disease. 
• 
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 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 5 of 24 
 
 
• 
Significant caffeine consumption within 8 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). 
• 
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 
3.5 
Study Assessments 
The following assessments will be done: 
 
Subset of Activities of Daily Living (ADLs) 
• 
Telemedicine, supervised and subject rated 
• 
At home, instructed and subject rated  
 
UPDRS Part III assessment  
• 
Telemedicine, modified Part III (tremor tasks only) 
 
CGI-S, I/PGI-S, I 
• 
Clinical Global Impression of Severity (CGI-S) & Improvement (CGI-I): The investigator 
or designee will rate the subject’s overall tremor severity & improvement. 
• 
Patient Global Impression of Severity (PGI-S) & Improvement (PGI-I): The subject will 
self-assess their overall tremor severity & improvement. 
 
Kinematic measurements performed with the Cala Trio device with motion sensors. 
3.6 
Safety 
The safety of the peripheral nerve stimulation will be characterized by the incidence of 
device and therapy-related adverse events. 
For this study, transient skin redness and/or itchiness lasting approximately less than 30 
minutes will not be considered an adverse event. Similarly, transient discomfort with 
stimulation will not be considered an adverse event; however, persistent pain from 
stimulation will be considered an adverse event. For a complete list of potential risks to the 
subject see Section 5.2.2. 
3.7 
Blinding 
Subjects and investigators/raters will not be blinded. 
3.8 
Sample Size 
Up to 50 subjects will be enrolled. 

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 6 of 24 
 
 
3.9 
Study Design Schematic 
 
Figure 2. Study schematic of the study design. 
3.10 Subject Recruitment 
The study site may use several methods to identify and recruit potential subjects.  These 
methods may include, but are not limited to, evaluation of subjects from their existing 
clinical practice, referrals from other physicians, review of available databases, or direct 
subject recruitment via advertising (with prior review and approval from Sponsor and 
reviewing IRB).   
3.11 Pre-Screening/Scheduling 
Prospective subjects may be pre-screened for the inclusion/exclusion criteria through an 
IRB approved script.  The subject will be informed that they do not have to answer any 
questions they would not like to answer. If the subject appears to meet the 
inclusion/exclusion criteria and chooses to participate, they will be scheduled for a 
screening visit via telemedicine. Once subject is scheduled for a screening visit, they will be 
asked to hold their last dose of their Parkinson’s medications prior to the visit. 
3.12 Informed Consent 
When a prospective subject has been identified and prior to beginning protocol-mandated 
testing, the study will be presented to them for consideration.  The subject will be given 
adequate time to have their questions answered and to carefully consider participation.  If, 
after understanding the purpose, potential risks and benefits, and requirements of the 
study, as well as their rights as a research subject, the individual agrees to participate, 
informed consent will be obtained.  Informed consent will be documented in the subject’s 
study records.   
3.13 Screening 
Following obtaining informed consent, potential subjects will undergo the following 
evaluations in order to ensure the subjects meet all of the inclusion criteria and none of the 
exclusion criteria:  
• 
Document current Parkinson’s disease medications and medicine schedule 
• 
Tremor Severity: MDS-UPDRS Part III will be performed. 
• 
Medical History: A brief medical history will be conducted to evaluate prior and 
existing medical conditions that may exclude individuals from the study. No medical 
records will be used for this study, so all eligibility criteria will be based upon self-

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 7 of 24 
 
 
reported information from each subject and in-person verification by qualified study 
staff. 
 
Subjects that don’t meet all of the inclusion criteria and meet any one of the exclusion 
criteria will be considered screen fails.  
3.14 Enrollment 
Prospective, eligible subjects are considered officially enrolled in the study after they have 
signed the informed consent, completed the screening stage, and are confirmed to satisfy all 
protocol-mandated inclusion and exclusion criteria. If a prospective subject chooses to 
withdraw during or just after the screening stage but before they begin use of the Cala Trio, 
they will be considered a screen fail and exited from the study; they will not be counted as 
enrolled. 
3.15 Visit 1 
Subjects will be reminded to be in the off state, i.e. to skip their last dose of PD medication, 
prior to their telemedicine Visit 1. The following assessments will occur: 
• 
Screening activities including medication review and medical history. No medical records 
will be used for this study, so all eligibility criteria will be based upon self-reported 
information from each subject and verification by qualified study staff. 
• 
Tremor assessments (while in the off state) including: 
o Modified MDS Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS) to 
confirm eligibility will be rated by the PI  
o Bain & Findley Activities of Daily Living (ADL) upper limb subset score will be 
rated by the subject based on their recall of the previous week (no props will be 
used) 
 
• 
Demographic information, Parkinson’s clinical characteristics, and wrist size and 
handedness will be collected based on self-reported information from subjects. 
Once a subject has been confirmed to be eligible for the study, a device kit containing a 
stimulator, base station and band will be shipped directly to the subject’s home ahead of 
Visit 2. 
3.16 Visit 2 
3.16.1 Visit 2a 
Once a subject has received the device kit, device training will occur via telemedicine, as 
follows: 
3.16.1.1.1 Positioning and Fastening Cala Trio 
Prior to device positioning, subjects should dampen the wrist of the prescribed hand to 
ensure good connection between the electrodes and wrist. Subjects should position the 
device on the prescribed hand such that the electrodes are positioned over the median and 
radial nerves, and securely tighten the band.  

A study of safety and efficacy of Transcutaneous Afferent Patterned Stimulation 
(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
Confidential and Proprietary 
This document is the property of Cala Health, Inc.  
Page 8 of 24 
 
 
3.16.1.1.2 Device Calibration 
To calibrate the Cala Trio device, subjects will perform a series of postural hold tremor 
tasks, in which the device measures the subject’s tremor frequency and sets the stimulation 
burst frequency based on the measured tremor frequency.  
For the purposes of this study, only the outstretched postural hold tremor task will be used. 
3.16.1.1.3 Setting Stimulation Intensity 
The subject will set the stimulation intensity to an amount they can comfortably tolerate 
while doing light activities. Paresthesia should be perceived in the parts of the hand and/or 
fingers innervated by the median and radial nerves. The stimulation intensity selected 
during the initial amplitude calibration is saved on the device for subsequent sessions. The 
subject can decrease or turn off the stimulation at any point in time, and may adjust their 
stimulation intensity from session to session to maintain the minimum paresthesia 
threshold.  
3.16.1.1.4 Device Training 
During the course of the visit, study personnel will instruct the subject on proper use of the 
device. Subjects must demonstrate competence to operate the device and comprehension of 
the instructions for use prior to completing the training. 
3.16.2 Visit 2b 
Once a subject is trained on the device, the subject will receive a single 40-minute therapy 
session with their Cala Trio. The subject will be asked to not stimulate at least 8 hours prior 
to this visit. The following assessments will be made prior to the therapy session and again 
immediately post the therapy session:  
o Tremor assessments (while in the off state) including: 
§ 
Modified MDS Unified Parkinson’s Disease Rating Scale Part III (MDS-
UPDRS) be rated by the PI  
§ 
Bain & Findley Activities of Daily Living (ADL) upper limb subset score 
will be rated by the subject. The ADL assessment will be performed using 
the subject’s own household props 
o CGI-S, I/PGI-S, I 
§ 
Clinical/Patient Global Impression of Severity (CGI-S/PGI-S): The 
investigator or designee (CGI) and Patient (PGI) will rate the overall 
tremor severity prior to stimulation  
§ 
Clinical/Patient Global Impression of Improvement (CGI-I/PGI-I): The 
investigator or designee (CGI) and Patient (PGI) will rate the overall 
tremor improvement following stimulation  
 
Additionally, the Cala Trio will direct the subject to perform the outstretched postural 
hold tremor tasks before and after the stimulation session to measure tremor power. 
Finally, subjects will input their Patient Session Impression of Improvement (PSI-I) 
rating on the device after the stimulation session 
 
Visits 2a and 2b may be combined into a single Visit 2. 
3.17 Home-Usage  

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The home use portion of the study will last 4 weeks. It will include: 
 
• 
2 stimulation sessions/day preferably at the same time every day-recommended as one 
in the morning and one in the evening. 
 
• 
Motion Data on device before and after each stimulation session. Cala Trio will direct the 
subject to perform postural hold tremor tasks before and after the stimulation session to 
measure tremor power. Additionally, subjects will input their Patient Session Impression 
of Improvement (PSI-I) rating on the device after the stimulation session 
 
• 
Weekly Bain & Findley Activities of Daily Living (ADL) upper limb subset score will be 
rated by the subject based on their recall of the previous week (no props will be used) 
 
• 
Device factory reset of the Cala Trio will occur on Day 14 of treatment via a call with study 
staff  
3.18 Visit 3/Study exit 
Subjects will be reminded to be in the off state, i.e. to skip their last dose of PD medication, 
prior to their telemedicine Visit 3/Study exit. The subject will be asked to not stimulate at 
least 8 hours prior to this visit. The subject will receive a single 40-minute therapy session 
with their Cala Trio. The following assessments will be made prior to the therapy session 
and again immediately post the therapy session:  
• 
Tremor assessments (while in the off state) including: 
o Modified MDS Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS) be 
rated by the PI  
o Bain & Findley Activities of Daily Living (ADL) upper limb subset score will be 
rated by the subject. The ADL assessment will be performed using the subject’s 
own household props 
• 
CGI-S, I/PGI-S, I 
o Clinical/Patient Global Impression of Severity (CGI-S/PGI-S): The investigator or 
designee (CGI) and Patient (PGI) will rate the overall tremor severity prior to 
stimulation  
o Clinical/Patient Global Impression of Improvement (CGI-I/PGI-I): The 
investigator or designee (CGI) and Patient (PGI) will rate the overall tremor 
improvement following stimulation  
 
• 
Product/preference survey 
 
• 
Subjects will return all study materials with provided shipping packages  
 
A factory device reset and re-calibration may be required if the device does not prompt a 
tremor task measurement of postural hold prior to starting the stimulation session. 
All subjects will be informed of their right to withdraw from the clinical study at any time 
without penalty or loss of benefits.  The Investigator may prematurely discontinue any 
subject from the study if the Investigator feels that the subject can no longer fully comply 
with the requirements of the study or if any of the study procedures are deemed potentially 
harmful to the subject. 

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3.19 Subjects Compensation 
In order to compensate subjects for their time and effort, they will be paid an amount as 
listed on the site-specific Informed Consent Form (ICF).   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.0 Schedule of Assessments 
The following table outlines the schedule of assessment for subjects throughout the entire 
duration of the study. 
 
Table 1. Schedule of Assessments 
 
Assessment 
 
Visit 1 
(screening/ 
enrollment) 
 
Visit 2a/b 
(device  
calibration/ 
training) 
 
Home Use 
 
 
Visit 3 
(Study Exit) 
 
After device 
is returned 
to Cala 
 
Time  
 
Day -7  
 
Day -1/0 
(+ 7 days) 
 
Days 1-28  
 
Day 28 
(+ 7 days) 
 
N/A 
PI or designee 
Informed Consent 
X 
 
 
 
 
Medical History & Demographics 
X 
 
 
 
 
Medication Review 
X 
 
 
 
 
UPDRS modified Part III  
X 
 
 
 
 
Confirmation of Subject Eligibility 
X 
 
 
 
 

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5.0 Risk and Benefit Assessment 
5.1 
Justification for the Study 
While there are medications available to Parkinson’s disease patients, they are not always 
effective in treating hand tremor.  Another common treatment option is DBS, which, while 
effective, is highly invasive and risky.  Therefore, effective alternative, non-pharmacologic 
treatment for Parkinson’s disease may prove to be of value. The Cala Trio is a treatment 
alternative that is non-invasive, reversible, and potentially lower risk than currently 
available therapies. 
5.2 
Description and Analysis of All Potential Risks to Subjects 
5.2.1 
Risk Categories 
Cala Health believes the investigational Cala Trio device and this study are nonsignificant 
risk as defined by the US IDE regulations (21 CFR 812). 
5.2.2 
Potential Risks and Protection against Risks 
5.2.2.1 
Potential Risks 
The risks associated with the Cala Trio device are similar to those risks observed in the 
routine clinical use of commercially available transcutaneous electrical nerve stimulators 
(TENS devices) or cutaneous-placed electrodes.  Cala Health’s previous clinical study of a 
similar device showed a 2% chance of significant and persistent skin irritation (including 
redness, itchiness, and/or swelling), a 1% chance of stinging pain in the wrist, and a 1% 
chance of a feeling of weakness in the wrist.  All incidences resolved without treatment or 
sequelae, and there were no serious adverse events.  
Possible minor risks/adverse reactions that may occur with the use of the Cala Trio device 
and in this study are:  
• 
Discomfort with stimulation (e.g. stinging, sensation of weakness, etc.) 
• 
Allergic reaction to electrodes or other materials 
UPDRS modified Part III (pre/post 
stim) 
 
X 
 
X 
 
CGI-S/I 
 
X 
 
X 
 
Cala 
Device Calibration & Training 
 
X 
 
 
 
Final device upload and device 
unassignment followed by factory reset 
 
 
Factory reset 
on Day 14 
 
X 
Subject  
Stimulation & PSI-I 
 
X 
2x per day 
X 
 
Kinematics 
 
Pre/Post stim 
Pre/Post stim Pre/Post stim 
 
B&F ADLs (recall) 
X 
 
1x per week 
X 
 
B&F ADLs (pre/post stim) 
 
X 
 
X 
 
PGI-S/I 
 
X 
 
X 
 
Product Survey 
 
 
 
X 
 
ALL 
 Adverse Events 
X 
X 
X 
 
X 
 

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• 
Skin irritation, including redness and/or itching 
Possible adverse reactions that are more serious, but less likely to occur, with the use of the 
Cala Trio device and in this study are:  
• 
Signs of significant skin irritation, sores, electrical burns or lesions at the site of 
stimulation 
• 
Significant and persistent increase in muscle tightness or stiffness 
• 
A feeling of chest pressure during stimulation 
• 
Swelling of the arm, wrist, or hand 
5.2.2.2 
Protection against Risks: 
The Cala Trio device will be used in the clinical study in accordance to the instructions for 
use provided with the investigational device.  The instructions for use disclose the above 
risks and appropriate actions to take if these events should occur (e.g., stop using the device, 
notify the investigator, etc.). 
Some subjects may find the tingling sensation from the stimulation to be unpleasant. To 
mitigate this risk, subjects will always have control over the stimulation level and may 
reduce or discontinue a stimulation level at any point in time. 
To further minimize risk, subjects will be trained on device usage by a study staff member 
prior to using the device at-home and must demonstrate ability to successfully operate the 
device.  
To mitigate the chance of adverse events occurring, all subjects participating in the study 
are evaluated and monitored during the study.  
The relatively low current (<8 mA) electrical stimulation administered in this study is 
applied to the wrist, away from vital organs such as the heart.  Therefore, this study does 
not pose any electrical safety hazard to the subject.   
5.2.3 
Minimization of Risks 
5.2.3.1 
Design Considerations 
Cala Health has designed the Cala Trio device to minimize the risk posed to study subjects. 
The stimulator pulses are safe, observe charge delivery thresholds and safeguards, and are 
within the range of those used clinically for TENS devices [24].  The Cala Trio device delivers 
lower levels of energy than many commercially available transcutaneous stimulation 
devices, so Cala Health expects fewer potential complications and risks for the Cala Trio 
device. 
5.2.3.2 
Stimulation- current unable to be delivered 
If the Cala Trio device were to malfunction and electrical current could not be delivered, this 
would not present a potential for serious risk to the health, safety or welfare of the subject.   
The effect would be that the subject would not receive stimulation and would require 
returning the malfunctioning device to the study site.  

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5.3 
Potential Benefits 
The subject’s hand tremor may improve while in this study; however, this will not be 
guaranteed or promised to a subject.  
5.4 
Alternatives for Participation 
Subject participation in this study is voluntary.  Should the subject elect not to participate, 
alternatives to participation include medications and/or surgical options.  
6.0 Clinical Event Definitions and Reporting 
6.1 
Definitions 
6.1.1 
Adverse Event 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device.   
6.1.2 
Adverse Event Rate 
The adverse event rate is defined as percentage of subjects who experienced an adverse 
event. 
6.1.3 
Serious Adverse Event 
A SAE is an adverse event that either: 
• 
Led to death 
• 
Led to serious deterioration in the health of the subject, that either resulted in:  
• 
A life-threatening illness or injury 
• 
A permanent impairment of a body structure or a body function 
• 
In-subject hospitalization or prolonged hospitalization 
• 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
• 
Led to fetal distress, fetal death or a congenital abnormality of birth defect.   
6.1.4 
Unanticipated Serious Adverse Device Effect 
An unanticipated serious adverse device effect (UADE) is a serious adverse effect, which by 
its nature, incidence, severity, or outcome has not been identified, in the current version of 
the risk analysis report.   
An anticipated serious adverse device effect (ASADE) is an effect that by its nature, 
incidence, severity or outcome has been identified in the risk analysis report.   
6.2 
Adverse Event Reporting 
AE information will be collected from subject enrollment through study exit.  AEs that occur 
during this study should be treated by established standards of care that will protect the life 
and safety of the subject.   
The Investigator will report any AEs to the Sponsor and will assess AEs for their 
relationship to the device and therapy, and whether or not the event meets the definition of 

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serious.  Subsequent intervention required, resolution status and whether or not the AE 
resulted in the subject’s discontinuation in the study will also be reported.   
Any SAE or UADE must be reported to the Sponsor within 24 hours of knowledge of the 
event.  The Investigator is responsible for notifying the Institutional Review Board (IRB), as 
required by the site-specific IRB requirements.    
All AEs must be recorded, as applicable, on the case report forms provided.   
6.3 
Device Observations and Malfunctions 
A device malfunction is defined as failure of an investigational medical device to perform in 
accordance with its intended purpose when used in accordance with the instructions for 
use.   
All device malfunctions are required to be documented on a case report form, reported to 
the Sponsor and, if required, reported to the IRB within the required timeframe.   
In the event of a suspected device malfunction or device observation, the device and 
accessories will be returned to the Sponsor for analysis. Instructions for returning the 
device will be provided by the Sponsor. 
All device malfunctions will be evaluated by Cala Health staff.  Serious injuries and/or 
deaths during the study will be evaluated to determine if the Cala Trio device might have 
malfunctioned or contributed to the event.  
 
7.0 Data Quality Assurance 
7.1 
Data Collection and Storage 
Data will be collected using case report forms (CRFs) designed specifically for this study. 
The data will be analyzed by Cala Health staff and reviewed by the investigators and a 
biostatistician, as needed. Investigators will be responsible for completion and timely 
submission of the forms to Cala Health for data processing. 
Cala Health quality assurance procedures are designed to ensure that complete, accurate, 
and timely data are submitted, that protocol requirements are followed, and that 
complications and adverse device effects are reported.  Incoming data are reviewed to 
identify inconsistent or missing data and adverse effects.  Data problems will be addressed 
in calls to the investigational site and during site visits.   
Collected data will be stored on paper documents or on a 21 CFR Part 11-compliant 
electronic data capture (EDC) system.  All paper documents will be securely stored at the 
study sites. Each subject’s data will be de-identified by assigning a unique identification 
number per subject. This identification number will be assigned by the researchers at the 
time of consent. The identification number will be securely stored at the study site, and only 
researchers involved in the study will have access to the information in the cabinet.   
Investigators are to maintain all source documents as required by the protocol, including 
worksheets and Informed Consent forms.  The source documents can be used by Cala Health 
staff (as needed) to verify information submitted on the CRFs. 

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8.0 Site Training 
The Sponsor, or designee, is responsible for the training of clinical site personnel, including 
the Investigator, sub-investigator(s), research coordinator(s), and other participating site 
staff.  The Sponsor will conduct initial training on Cala Trio use, data collection, proper 
reporting of AEs, compliance with the protocol, informed consent process and associated 
activities necessary to conduct this clinical study in accordance with the regulations and 
Good Clinical Practices.  
8.1 
Protocol Deviations 
Any deviations from the study plan identified during monitoring visits or through other 
means will be documented on CRFs. These include, but are not limited to items such as the 
following:  
• 
Failure to obtain written informed consent prior to conducting study related 
measurements 
• 
Subject enrolled that does not meet inclusion/exclusion criteria 
• 
Subject received stimulation using the wrong device (i.e. a right-handed device was 
used on the left wrist or a device of the wrong size was used) 
If the study site demonstrates a pattern of consistent and frequent deviations, the Sponsor 
will undertake appropriate activities (e.g. re-training) to attempt to bring the site into 
compliance with the protocol. A pattern of repeated serious deviations from the protocol 
may result in site termination from the study.  
9.0 Statistical Methods 
9.1 
General Principles 
Standard summary statistics will be calculated for all study variables.  For continuous 
variables, statistics will include means, standard deviations, medians and interquartile 
ranges.  Categorical variables will be summarized in frequency distributions. 
One-sided statistical tests will have p-values less than 0.025 deemed significant while two-
sided tests will have p-values less than 0.05 deemed significant.  Statistical analyses will be 
conducted in SAS version 9.3 or above (SAS Institute, Cary, N.C.), R version 3.2 or above (R 
Foundation for Statistical Computing, Vienna, Austria) or another validated statistical 
software package. 
9.2 
Safety Endpoint Analysis 
The safety of the Cala Trio 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. 
9.3 
Primary Effectiveness Endpoints Analyses 
Primary endpoint for the study is defined as within subject comparison of tremor power 
before stimulation to after stimulation. Statistical testing of the primary endpoint will be 

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based on the cohort of all enrolled and treated subjects for whom outcome data are 
available. 
The statistical objective related to the primary endpoint is to demonstrate that Parkinson’s 
disease action hand tremor is reduced from pre-stimulation values at baseline to post-
stimulation values at 4 weeks, under treatment with the Cala Trio device.  Formally, the null 
and alternative hypotheses to be tested for each primary endpoint are as follows: 
H0: µT ≥ 0  
HA: µT < 0  
where µT is the change from pre-stimulation at baseline to post-stimulation at 4 weeks in 
the endpoint in question. 
9.4 
Secondary Effectiveness Endpoint Analysis 
The study secondary endpoint is defined as within subject comparison of ADLs and UPDRS 
across Visit 1-3 captured as defined in the protocol.  Statistical analyses will be performed 
incorporating intra-subject correlation for repeated measures, and as for the primary 
endpoint the statistical objective is to demonstrate that Parkinson’s disease action tremor is 
reduced under treatment with the Cala Trio device. 
Null and alternative hypotheses are analogous to those shown above. 
9.5 
Additional Exploratory Effectiveness Analyses 
Additional exploratory analyses include: 
• 
Patient Session Impression of Improvement (PSI-I) 
• 
UPDRS modified Part III (tremor tasks only) – subset relevant to non-stimulated 
hand 
• 
UPDRS modified Part III (tremor tasks only) and ADL pre- versus post-stimulation 
within each visit 
• 
ADLs based on recall 
• 
Product Survey 
• 
Device usage metrics 
• 
CGI-S/I, PGI-S/I 
 
Note that the same UPDRS modified Part III (tremor tasks only) are collected on the non-
stimulated hand in order to determine if the device has a bilateral effect.  
The listed analyses will be evaluated using analogous statistical methods as described for 
the primary and secondary endpoints.  
 
9.6 
Planned Analyses 
All participants in this study will be using the same device as the commercial users of Cala 
Trio diagnosed with ET, with a common user interface workflow. As with all commercial 
users, an accelerometer on the device will measure tremor power before and after a subset 
of 40-minute therapy sessions (every session for the first 40 sessions, followed by every 7th 
session thereafter). Subject-reported ratings of the therapy sessions (improved, no change, 
worsened) will be recorded after the acceleration measurements on the device. 

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The analysis will evaluate de-identified data from up to 50 subjects who complete Cala Trio 
therapy sessions during 4 weeks of at-home use. Subjects will be given instruction on how 
to calibrate the device’s stimulation to their hand tremor frequency and will be instructed to 
use the therapy twice daily at home. Therapy efficacy will be quantified using improvement 
in tremor power pre- and post- stimulation. Tremor severity will be visually rated for all 
subjects by an expert rater according to UPDRS and the ADL score will be noted. 
 
Formal analyses of the primary and secondary endpoints will be conducted after completion 
of study.  It will take place once 50 subjects have reached the 4-week visit, at which time 
analyses subgroups of interest will also be investigated, tabulated and reported. 
Study hypotheses will be tested for p-values of 0.05 and 0.01. 
9.7 
Sample Size and Power 
The study sample size (N) is predicated on primary endpoints as detailed above. Assuming 
same effect from the ET-14 data, at p = 0.01 we have the following results.  
 
 
Metric 
p value 
N 
Kinematic measurements for study duration of 
2 weeks 
 
Kinematic measurements for study duration of 
4 weeks 
0.01 
 
 
0.01 
40 
 
 
30 
 
Under these effect sizes, assuming up to 10% data attrition and with a paired difference test 
at 0.01 alpha against the null hypothesis of no change from baseline, the 34 to 50 subject 
analysis provides at least 90% power for simultaneous testing of the primary endpoint.  
 
10.0 Study Administration 
10.1 Institutional Review Board Approval 
The study protocol will be reviewed and approved by the Investigator’s IRB prior to subject 
enrollment. The Sponsor and the IRB prior to implementation must approve proposed 
significant changes to the clinical study protocol.  A significant change is one which may 
increase the risk or present a new risk to a subject, affects the subject’s rights or welfare, or 
which may adversely affect the scientific validity of the study. 
Investigators are responsible for obtaining and maintaining annual renewal of the study by 
their IRB (or according to renewal schedule imposed by the IRB).   
10.2 Amending the Protocol 
The protocol, subject informed consent, or other clinical investigation documents shall be 
amended as needed throughout the clinical investigation. Proposed amendments to the 
protocol shall be agreed upon between the Sponsor and Investigator (or delegate). The 
amendments to the protocol and the subject's informed consent form shall be notified to, or 

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approved by, the IRB and regulatory authorities. The version number and date of 
amendments shall be documented. 
10.3 Privacy and Confidentiality 
Subject data obtained in connection with this clinical study will be treated as confidential 
and will be disclosed only as required by law.  A number will identify subjects, not a name.  
The subject informed consent discloses how subject information is collected and used, and 
all subjects must consent in writing prior to any study-related treatments.   
10.4 Record Retention 
Investigators will maintain complete, accurate and current study records in accordance to 
the requirements in the IDE regulation (21 CFR 812).  
These records shall be maintained for a period of two years after the latter of the following 
two dates:  the date on which the investigation is terminated or completed, or the date that 
the records are no longer required for purposes of supporting a regulatory submission. 
10.5 Device Accountability 
Device accountability records will be maintained at the study site. Devices used during the 
study will be recorded in the device accountability and disposition logs.  
10.6 Sponsor Responsibilities 
The Sponsor (Cala Health, Inc.) is responsible for: 
• 
Ensuring that the study is designed and managed in compliance with all appropriate 
regulatory standards and is conducted according to the protocol 
• 
Selecting qualified investigators and providing them with the information and 
materials necessary to conduct this study in compliance with the protocol and local 
applicable regulatory requirements 
• 
Providing appropriate training to Investigators, site staff and all sponsor 
representatives to conduct this study in compliance with the protocol and local 
applicable regulatory requirements 
• 
Securing compliance with the clinical protocol, investigator agreement, and local 
regulations 
• 
Confirming that IRB review and approval are obtained prior to subject enrollment or 
conducting protocol-required testing 
• 
Ensuring that the Investigators and the reviewing IRB are promptly notified of 
significant new information about this clinical study 
 
• 
Supervising the overall conduct of the study: ensuring proper monitoring of the clinical 
study and data, analyzing data (including evaluations of AEs) and preparing study 
reports 
• 
Controlling the distribution of the device(s) under investigation. 
10.7 Investigator Responsibilities 
The Investigator is responsible for the following:  

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• 
Ensuring sufficient time and resources (including qualified staff and facilities) are 
available to manage the day-to-day conduct of the study, and ensuring data integrity 
and the rights, safety and well-being of subjects 
• 
Obtaining approval from the IRB, including subsequent protocol amendments and 
changes to the subject informed consent and obtaining renewals throughout the 
duration of the study 
• 
Compliance with the clinical study protocol and applicable regulatory requirements 
• 
Investigational device accountability and use of the investigational device in 
accordance with the approved protocol 
• 
Reporting all SAEs to the Sponsor as soon as possible after knowledge of the event, and 
to the IRB as specified in the requirements. 
 
11.0 Publication 
The Sponsor may disclose the results of the study through a publication or any other public 
disclosure.  A Publications Review Committee may be formulated to oversee the publication 
process.  Authorship on a primary publication of the results from this study will be based on 
contributions to study design, enrollment, data analysis, and interpretation of results.   

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12.0 References 
[1] Nonnekes J et al Unmasking Levodopa Resistance in Parkinson’s Disease. Movement 
Disorders 2016. 
[2] Yahr MD, Duvoisin RC, Schear MJ, Barrett RE, Hoehn MM. Treatment of parkinsonism 
with levodopa. Arch Neurol 1969; 21(4):343-354. 
[3]  Louis, E. D. (2015). More Time with Tremor: The Experience of Essential Tremor 
Versus Parkinson's Disease Patients. Movement Disorders Clinical Practice. 
[4]  Walsh, D. M., Howe, T. E., Johnson, M. I., Moran, F., & Sluka, K. A. (2009). 
Transcutaneous electrical nerve stimulation for acute pain. The Cochrane Library. 
[5]  Dubinsky, R. M., & Miyasaki, J. (2010). Assessment: Efficacy of transcutaneous electric 
nerve stimulation in the treatment of pain in neurologic disorders (an evidence-based 
review) Report of the Therapeutics and Technology Assessment Subcommittee of the 
American Academy of Neurology. Neurology, 74(2), 173-176. 
[6]  Vance, C. G., Dailey, D. L., Rakel, B. A., & Sluka, K. A. (2014). Using TENS for pain 
control: the state of the evidence. Pain management, 4(3), 197-209. 
[7]  Yoo, P. B., Hincapie, J. G., Hamann, J. J., Ruble, S. B., Wolf, P. D., & Grill, W. M. (2011, 
August). Selective control of physiological responses by temporally-patterned 
electrical stimulation of the canine vagus nerve. In Engineering in Medicine and Biology 
Society, EMBC, 2011 Annual International Conference of the IEEE (pp. 3107-3110). 
IEEE. 
[8]  Birdno, M. J., Kuncel, A. M., Dorval, A. D., Turner, D. A., Gross, R. E., & Grill, W. M. (2012). 
Stimulus features underlying reduced tremor suppression with temporally patterned 
deep brain stimulation. Journal of neurophysiology, 107(1), 364-383. 
[9]  Brocker, D. T., Swan, B. D., Turner, D. A., Gross, R. E., Tatter, S. B., Koop, M. M., ... & Grill, 
W. M. (2013). Improved efficacy of temporally non-regular deep brain stimulation in 
Parkinson's disease. Experimental neurology, 239, 60-67. 
[10] Miocinovic, S., Khemani, P., Whiddon, R., Zeilman, P., Martinez-Ramirez, D., Okun, M. S., 
& Chitnis, S. (2014). Outcomes, management, and potential mechanisms of 
interleaving deep brain stimulation settings. Parkinsonism & related disorders, 20(12), 
1434-1437. 
[11] Tass, P. A., Qin, L., Hauptmann, C., Dovero, S., Bezard, E., Boraud, T., & Meissner, W. G. 
(2012). Coordinated reset has sustained aftereffects in Parkinsonian monkeys. Annals 
of neurology, 72(5), 816-820. 
[12] Hanajima, R., Dostrovsky, J. O., Lozano, A. M., Hutchison, W. D., Davis, K. D., Chen, R., & 
Ashby, P. (2004). Somatosensory evoked potentials (SEPs) recorded from deep brain 
stimulation (DBS) electrodes in the thalamus and subthalamic nucleus (STN). Clinical 
neurophysiology, 115(2), 424-434. 

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(TAPS) for reduction of action tremor in Parkinson’s Disease (PD) 
Protocol PD-02 
Rev A; 1-OCT-2020 
 
 
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[13] Klostermann, F., Wahl, M., Schomann, J., Kupsch, A., Curio, G., & Marzinzik, F. (2009). 
Thalamo-cortical processing of near-threshold somatosensory stimuli in 
humans. European Journal of Neuroscience, 30(9), 1815-1822. 
[14] Brittain, J. S., Cagnan, H., Mehta, A. R., Saifee, T. A., Edwards, M. J., & Brown, P. (2015). 
Distinguishing the Central Drive to Tremor in Parkinson's Disease and Essential 
Tremor. The Journal of Neuroscience, 35(2), 795-806. 
[15] Cagnan, H., Brittain, J. S., Little, S., Foltynie, T., Limousin, P., Zrinzo, L., ... & Brown, P. 
(2013). Phase dependent modulation of tremor amplitude in essential tremor through 
thalamic stimulation. Brain, awt239. 
 
13.0 Revision History 
Protocol 
Version 
Summary of Changes 
Author 
 
A 
 
Initial Release 
 
Ruta 
Deshpande