Randomized Controlled Clinical Trial of Non-invasive Device to Alleviate Carpal Tunnel Syndrome
Phase: NA
Conditions: Carpal Tunnel Syndrome
Sponsor: Pressure Profile Systems, Inc.

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Aim 2 Trial Protocol 
 
Study Name 
Randomized Controlled Clinical Trial of Non-invasive Device to 
Alleviate Carpal Tunnel Syndrome 
Short Title 
Non-invasive CTS Device Clinical Trial 
Study ID  
PPS-CTS-SBIR2 
Ver. / Date 
3 / 2018 December 20 
Sponsor 
Pressure Profile Systems (PPS) 
5757 W Century Blvd, Ste 600, Los Angeles, CA 90045 
Funded By 
National Institute of Biomedical Imaging and Bioengineering (NIBIB) 
SBIR, R44 EB024713-01 
 
 
 
The information contained in this document is confidential and the proprietary property of 
Pressure Profile Systems. 
 
 
Approvals 
 
Name 
Title 
Signature and Date 
Jae Son 
CEO/Founder, PPS 
Feb 5, 2018 
Pauline Luong 
Clinical Research 
Manager 
 
 
 
 
 
 
 
 
 
signed 5/9/19 but protocol v3
IRB-approved 1/2/19

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Aim 2 Trial Protocol 
Study Name 
Randomized Controlled Clinical Trial of Non-invasive Device to 
Alleviate Carpal Tunnel Syndrome 
Short Title 
Non-invasive CTS Device Clinical Trial 
Study ID  
PPS-CTS-SBIR2 
Ver / Date 
3 / 2018 December 20 
INVESTIGATOR’S SIGNATURE PAGE  
I agree to: 
  
1. Implement and conduct this study diligently and in strict compliance with the protocol, 
good clinical practices and all applicable laws and regulations. 
  
1. Maintain all information in confidence and, when this information is submitted to an 
Institutional Review Board (IRB), Independent Ethics Committee (IEC) or another group, it will 
be submitted with a designation that the material is confidential. 
  
I have read this protocol in its entirety and I agree to all aspects. 
 
 
_______________________________ 
_______________________________ 
______________ 
  Investigator Printed Name 
  Signature 
  Date 
_______________________________ 
_______________________________ 
______________ 
  Investigator Printed Name 
  Signature 
  Date 
_______________________________ 
_______________________________ 
______________ 
  Investigator Printed Name 
  Signature 
  Date 
_______________________________ 
_______________________________ 
______________ 
  Investigator Printed Name 
  Signature 
  Date 
   
Acknowledged By: 
 
_____________________________ 
___________________________ 
_____________ 
Sponsor Representative, Printed 
Name 
  Sponsor Representative, Signature 
  Date 
Send signed/dated Investigator’s Signature Page to Sponsor 
 

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Aim 2 Trial Protocol 
TABLE OF CONTENTS 
1. 
Personnel & Facilities 
6 
2. 
Protocol Summary 
7 
2.1. 
Study Synopsis 
7 
2.2. 
Schedule of Events (SOE) 
8 
2.3. 
Study Procedures Flow-chart 
8 
3. 
INTRODUCTION 
10 
3.1. 
Background & Rationale 
10 
3.2. 
Study Device 
10 
3.3. 
Potential Risks & Benefits 
11 
3.3.1. 
Known Potential Risks 
11 
3.3.2. 
Known Potential Benefits 
11 
4. 
Objectives & Endpoints 
11 
5. 
Study Design 
13 
5.1. 
Overall Design 
13 
5.2. 
Scientific Rationale 
14 
6. 
STUDY POPULATION 
14 
6.1. 
Inclusion Criteria 
14 
6.2. 
Exclusion Criteria 
15 
6.3. 
Prior/Concomitant Medications or Therapies 
15 
6.4. 
Enrollment Determination 
16 
6.5. 
Screen Failures 
16 
6.6. 
Strategies for Recruitment & Retention 
16 
7. 
STUDY PROCEDURES 
16 
7.1. 
Screening, Informed Consent and HIPAA 
16 
7.2. 
Enrollment, Baseline Assessment, and Randomization 
17 
7.2.1. 
Enrollment Procedures 
17 
7.2.2. 
Subject ID Assignment 
17 
7.2.3. 
Baseline Assessment 
17 
7.2.4. 
Randomization 
17 
7.3. 
Treatment Period 
18 
7.4. 
Post-Treatment Period (Active Study Device Group) 
18 
7.5. 
Post-Treatment Period (Sham Device Group) 
18 

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7.6. 
Exit Procedures 
19 
7.7. 
Subject Withdrawal 
19 
8. 
Study Supplies 
19 
8.1. 
Study Device Supply 
19 
8.2. 
Study Device Reconciliation and Destruction 
19 
8.3. 
Other Study Supplies 
20 
9. 
SAFETY ASSESSMENTS 
20 
9.1. 
Specification of and Methods for Collecting Safety Parameters 
20 
9.2. 
Adverse Events and Serious Adverse Events 
20 
9.3. 
Reporting Procedures 
20 
9.4. 
Follow-up for Adverse Events 
20 
10. 
STATISTICAL CONSIDERATIONS 
21 
10.1. 
Statistical Hypotheses 
21 
10.2. 
Sample Size Determination 
21 
10.3. 
Randomization and Blinding Procedures 
22 
10.4. 
Population for Analyses 
22 
10.5. 
Statistical Analyses 
22 
11. 
DATA COLLECTION AND QUALITY ASSURANCE 
22 
11.1. 
Data Collection Methods 
22 
11.2. 
Data Management 
23 
11.3. 
Quality Assurance 
23 
11.4. 
Study Data & Records Retention 
24 
12. 
PARTICIPANT RIGHTS AND CONFIDENTIALITY 
24 
12.1. 
Institutional Review Board (IRB) 
24 
12.2. 
Informed Consent Forms 
25 
12.3. 
Participant Confidentiality 
25 
13. 
PUBLICATION OF RESEARCH 
25 
14. 
ABBREVIATIONS 
26 
15. 
REFERENCES 
27 
REVISION HISTORY 
28 
APPENDICES 
29 
APPENDIX I: BOSTON CARPAL TUNNEL QUESTIONNAIRE (BCTQ) 
30 

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APPENDIX II: NERVE CONDUCTION STUDY (NCS) 
33 
 
 
 

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1. 
Personnel & Facilities 
 
Sponsor 
Jae Son, Ph.D. 
Pressure Profile Systems, Inc. 
5757 W Century Blvd, Ste 600 
Los Angeles, CA 90045 
(310) 641-8228 
jaeson@pressureprofile.com 
NIH/NIBIB Program Officer 
Michael Wolfson, Ph.D. 
6707 Democracy Blvd, 
Democracy II, Suite 200, 
Bethesda, MD 20817 
(301) 451-4778 
michael.wolfson@nih.gov 
Research Site (#002) 
Zong-Ming Li, Ph.D. 
Cleveland Clinic 
9500 Euclid Ave, ND20 
Cleveland, OH 44195 
 
Research Site (#001) 
Frank J King, M.D. 
Mission Pain & Spine 
26932 Oso Pkwy #275, 
Mission Viejo, CA 92691 
 
Research Site (#003) 
David Nguyen, M.D. 
Southern California Permanente Medical Group 
100 S Los Robles, 5th Floor, 
Pasadena, CA 91101 
 
 
 
 
 
 
 
 

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2. 
Protocol Summary 
2.1. 
Study Synopsis 
Title 
Randomized Controlled Clinical Trial of Non-invasive Device to Alleviate 
Symptoms of Carpal Tunnel Syndrome 
Study Description Sham-controlled, multi-center and remote patient-centered randomized controlled 
clinical trial to investigate the efficacy of a novel non-invasive, unobtrusive study 
device in reducing symptoms of carpal tunnel syndrome (CTS). Daily wear of the 
study device is expected to significantly reduce symptom severity (evaluated by 
the Boston Carpal Tunnel Questionnaire) in mild to severe CTS-diagnosed 
patients. Subjects are randomized into the active device group or sham group for 
8 weeks, then followed for 12 weeks post-treatment. 
Objectives 
Primary: Investigate whether daily wear of the study device significantly reduces 
patient-reported CTS symptom severity. 
 
Secondary: Determine whether there is a difference between the active device 
group and sham group. Investigate whether changes in symptoms are sustained or 
continue post-treatment. 
Endpoints 
Primary: BCTQ-SSS of the treatment group at 8 weeks compared to Baseline.  
 
Secondary: BCTQ-SSS at 8 weeks and at post-treatment timepoints between the 
treatment and sham groups 
Study Population 
Sample size: 102 (51 in each arm) 
Adults diagnosed with mild to severe CTS, ages 21-65 of any gender 
Any geographic location within the United States 
Phase 
Confirmatory/pivotal 
Sites 
At least 3 physical sites located in the United States (national enrollment) 
Study Device 
Stiffness-optimized thermoplastic curved band that has a strong biocompatible 
adhesive in the center of the concave side of the device. Device is designed to 
decompress the median nerve and thus relieve symptoms of carpal tunnel 
syndrome. 
Study Duration 
Approximately 12 months 
Participant 
Duration 
5 months  
 
 
 
 

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2.2. 
Schedule of Events (SOE) 
Schedule of Events Table – Active Device Group 
Treatment Period (8wk) 
Post-Treatment Period (12wk) 
Wks Into Study 
0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
Enrollment1 
X* 
  
  
  
  
  
  
  
  
  
  
NCS2 
X* 
  
  
  
  
  
  
  
  
  
  
BCTQ3 
X* 
X* 
X* 
X* 
X* 
  
X* 
 
X 
  
X 
Follow-up4 
  
X* 
X* 
X* 
X* 
  
X* 
 
X 
  
X 
Usage Diary5 
  
X* 
X* 
X* 
X* 
  
  
 
 
 
 
User Survey6 
  
  
  
  
X* 
  
  
  
 
 
 
Day 
0 
14 
28 
42 
56 
70 
84 
98 
112 
126 
140 
 
Schedule of Events Table – Sham Device Group 
 
 
Treatment Period  
(8wk with Sham Device) 
Post-Rx 
Period 
Treatment Period 
(8 wk with Active Device) 
Wks Into Study 
0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
Enrollment1 
X* 
  
  
  
  
  
  
  
  
  
  
NCS2 
X* 
  
  
  
  
  
  
  
  
  
  
BCTQ3 
X* 
X* 
X* 
X* 
X* 
  
X* 
X 
X 
 X 
X 
Follow-up4 
  
X* 
X* 
X* 
X* 
  
X* 
X 
X 
 X 
X 
Usage Diary5 
  
X* 
X* 
X* 
X* 
  
  
X 
X 
X 
X 
User Survey6 
  
  
  
  
X* 
  
  
  
 
 
X 
Day 
0 
14 
28 
42 
56 
70 
84 
98 
112 
126 
140 
* = required 
 
 
 
1 - Enrollment includes completing ICF and baseline questions (eligibility check, CTS diagnosis/history, 
randomization, demographics, medical history) 
2 - NCS within 24 months required to enroll 
3 - BCTQ incorporated into Follow-up Surveys 
4 - Follow-up Surveys completed by patient online 
5 - Usage Diary completed online by patient DAILY 
6 - User Feedback Survey (feedback on design and use of device) completed by patient online. 
 
 
2.3. 
Study Procedures Flow-chart 
See next page 
 

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Screening: 
• 
Identify patients 
• 
Pre-screening Questionnaire 
• 
Eligibility Confirmation 
 
 
 
 
Enrollment: 
• 
BCTQ and NPRS 
• 
NCS if needed 
• 
Randomized 
• 
Study Devices Mailed 
 
 
 
Group A: Active Device 
 
Group B: Sham Device 
 
 
 
Follow-up 1 (Day 14): 
• 
BCTQ & NPRS 
• 
Daily Diary (up to 14) 
 
 
 
 
Follow-up 2 (Day 28): 
• 
BCTQ & NPRS 
• 
Daily Diary (up to 28) 
 
 
 
 
Follow-up 3 (Day 42): 
• 
BCTQ & NPRS 
• 
Daily Diary (up to 42) 
 
 
 
 
Follow-up 4 (Day 56): 
• 
BCTQ & NPRS 
• 
Daily Diary (up to 56) 
• 
User Feedback Survey 
 
 
 
 
 
Post-Treatment Follow-up 1 (Day 84): 
• BCTQ & NPRS 
 
Post-Treatment Follow-up 1 (Day 84): 
• 
BCTQ & NPRS 
• 
Offer Real Device Treatment 
 
 
Treatment with Active Device Start 
(Day 85) 
 
 
Post-Treatment Follow-up 2 (Day 
112):  
• BCTQ & NPRS  
 
Follow-up 1 (Day 98): 
• 
BCTQ & NPRS 
 
 
Follow-up 2 (Day 112): 
• 
BCTQ & NPRS 
 
 
Post-Treatment Follow-up 3 (Day 
140):  
• 
BCTQ & NPRS 
 
Follow-up 3 (Day 126): 
• 
BCTQ & NPRS 
 
 
Follow-up 4 (Day 140): 
• 
BCTQ & NPRS 
• 
User Feedback Survey 
 
 
 
Exit Study 
 

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3. 
INTRODUCTION 
3.1. 
Background & Rationale 
Carpal tunnel syndrome (CTS) is one of the most common peripheral neuropathies and the 
most well-known workplace repetitive stress injury.1-4 The carpal tunnel is located at the wrist and 
is composed of the eight carpal bones and the transverse carpal ligament. The median nerve travels 
through the carpal tunnel at the wrist and may become entrapped due to inflammation, awkward 
wrist postures, repetitive hand motions, or other causes. Compression impairs normal median nerve 
function, which leads to paresthesia, pain, numbness, and other symptoms in the distribution of the 
median nerve. Chronic compression may lead to irreversible nerve damage, significant impairment 
of hand function, and muscle atrophy.1,4 
Commonly, CTS is first addressed with conservative treatment options, including wearing 
wrist braces or splints, lifestyle changes, or the use of oral non-steroidal anti-inflammatory agents 
(NSAIDs).3-6 Although wrist splints are prescribed at night and as much as possible during the day, 
fulltime compliance is poor.7 Patients may elect to receive a steroid injection into the wrist, but the 
procedure is hazardous3 and the effects are short-term. Repeat injections are not recommended. 
Severe cases of CTS are often referred directly to surgery to prevent further nerve damage. 
Approximately 70-90% of carpal tunnel release (CTR) surgeries have good to excellent long-term 
outcomes,4 but, like all operations, there are risks associated with CTR surgery. Some of these risks 
include injury to the median nerve, its branches, vessels or tendons; infection; and scar sensitivity.8 
In a review of 186 CTR cases, about 24% of patients experienced mild residual symptoms and 8% 
experienced recurrent or persistent problems.3 
The shortcomings of current conservative treatment options and the fear of invasive 
procedures, scarring, or return of symptoms after surgery motivate several patients to explore other 
conservative, non-invasive treatment options.  
 
3.2. 
Study Device 
The study device is a stiffness-optimized thermoplastic curved band that has a strong 
biocompatible adhesive in the center of the concave side of the device. Similar to other non-invasive 
devices for CTS, the study device is a Class I device that requires Food and Drug Administration 
(FDA) registration but does not require 510(k) clearance.  
Unlike the majority of traditional and dynamic splints, the study device was developed to 
decompress the median nerve without excessive applied force and cumbersome usage 
requirements. The design of the study device allows for free movement of the wrist with minimal 
impediment of daily activities. 
The study device is indicated for people who have been diagnosed with mild to severe carpal 
tunnel syndrome. It is fit to the subject based on the criteria in the Instructions for Use. 

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The sham device is similar to the active study device but with a conformable cushion attached 
to the underside to prevent the main mechanism of action. Neither the sham nor the active study 
device contain any medicinal substances or electromagnetic properties that could affect human 
tissue. 
The active study device and the sham device should be stored at room temperature. 
3.3. 
Potential Risks & Benefits 
3.3.1. 
Known Potential Risks 
Immediate risks related to the device include skin irritation or reaction to the 
adhesive used on the device, and discomfort related to any forces that the device applies to 
the wrist. 
Previous studies have found the study device can be worn for over 12 hours with 
little to no discomfort and minor to no redness.9 
The sham device is the same as the active device but with a cushion on the underside. 
This cushion is similar to sponges used for make-up or healthcare applications. 
3.3.2. 
Known Potential Benefits 
Prolonged wear (anywhere from 1 week to 4 weeks) of the study device may 
reduce symptoms of CTS.9 
The sham device may cause a placebo effect and reduce symptoms of CTS as well. 
 
4. 
Objectives & Endpoints 
Objective 
Endpoints 
Explanation 
Primary 
Investigate whether daily 
wear of the study device 
significantly reduces 
patient-reported CTS 
symptom severity. 
Symptom Severity Score (SSS) 
of the Boston Carpal Tunnel 
Questionnaire (BCTQ) in the 
treatment group at 8 weeks 
compared to Baseline.  
The SSS is a validated 
combined measure of the 
patient’s perception of the 
level and frequency of pain, 
numbness, tingling caused by 
CTS. 8 weeks is the end of 
the treatment period. 
Secondary 
Determine whether there is a 
difference between the 
active device group and 
sham group.  
Comparing SSS at 8 weeks and 
between the active device 
group and sham group. 
Between group comparison 
conducted for the primary 
outcome variable at the 
primary endpoint (8 weeks).  

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Additionally, we will 
determine if this difference 
continues post-treatment. 
Comparing SSS 1 month post-
treatment (12 weeks) between 
the active device group and 
sham group. 
Single timepoint at 12 weeks 
compared between groups for 
post-treatment analysis. 
Exploratory 
Does CTS symptom 
improvement occur before 8 
weeks? 
Significant reduction in SSS 
compared to Baseline at any 
time point before 8 weeks. 
Identification of significant 
SSS reduction before 8 weeks 
suggests a shorter minimum 
duration of wear. 
Do unilateral and bilateral 
CTS patients respond 
differently to treatment? 
Change in SSS at 4 and 8 
weeks in a unilateral subgroup 
compared to a bilateral 
subgroup. 
Unilateral patients showed 
significant SSS improvement 
in the pilot study, whereas 
bilateral patients seemed to 
show none.9 Both 4- and 8-
week timepoints compared in 
case a difference is seen 
before the end of treatment. 
Do patients respond 
differently based on 
Baseline severity? 
Change in SSS at 4 and 8 
weeks in mild, moderate, and 
severe subgroups. 
AANEM guidelines 
categorize CTS into 3 
severity groups. 
Describe the effect of study 
device treatment on patients 
with hormonal-induced 
CTS, such as pregnancy. 
Change in SSS at or within 8 
weeks in a subgroup of 
pregnant women. 
The study device is 
hypothesized to work 
primarily for repetitive stress 
induced CTS. Pregnant 
women often develop CTS 
due to swelling of the tissue. 
Demonstrate high subject 
compliance. 
Diary wear time responses. 
Number of dropouts due to 
non-compliance. 
Compliance is measured by 
adherence to daily wear and 
actual vs advised wear time. 
Obtain user feedback on the 
comfort, use, and design of 
the study device. 
User Feedback Survey 
responses at the end of 
Treatment Period 
Collects qualitative data on 
practical aspects of the 
device. 
 

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5. 
Study Design 
5.1. 
Overall Design 
It is hypothesized that daily wear of the study device will result in significant improvements in 
patient-reported symptom severity. It is also hypothesized that the effects from active study device 
treatment will be significantly greater than effects from sham treatment. In both cases, it is 
hypothesized that improvements will be sustained post-treatment. 
This study is designed as a randomized, double-blind, sham-controlled, two-arm trial 
consisting of an eight-week treatment period (active study device or sham), followed by one 
required follow-up four weeks later (at week 12). After the required follow-up evaluation, the active 
device group can optionally continue to report symptom changes for an additional 8 weeks. The 
sham group participants can elect to wear the active study device for 8 weeks after completing their 
week 12 follow-up evaluation of the sham device. For both groups, completion through the optional 
follow-ups results in a 5-month patient duration. 
There are two study groups: the active device group receiving the active study device and the 
sham group receiving a non-active sham device. Subjects will be informed that they have a 50:50 
chance of receiving treatment or a sham. They will also be informed that if they receive sham 
device, they will be offered the active device 4 weeks into the post-treatment period. However, all 
subjects will not know what treatment they are on until the conclusion of the trial. Study devices 
are shipped directly to enrolled subjects from the Sponsor’s designated shipping associate, which 
blinds site staff to group assignment.  
There are (at minimum) three physical research sites but subjects are primarily enrolled 
remotely. The physical research sites are clinics that local subjects can physically go to if needed 
(e.g., medical concern, AE). Enrolled subjects are assigned to the PI of the geographically closest 
physical site. 
Subjects are enrolled following confirmation of CTS in one or both wrists via a recent Nerve 
Conduction Study (NCS) and are asked to wear the assigned device daily for 8 weeks. The NCS is 
an electrodiagnostic technique used to confirm clinical diagnosis of CTS, with a 56% to 85% 
sensitivity and at least 95% specificity for CTS.15 The primary outcome measure, Symptom 
Severity Score (SSS) of the Boston Carpal Tunnel Questionnaire (BCTQ), is evaluated at: 
● Baseline 
● Once every 2 weeks during the 8-week treatment period 
● 4 weeks after the end of treatment (at week 12) 
 
After week 12, the active device group can continue to complete follow-ups every 4 weeks for 
another 8 weeks. At the end of week 12, the sham group will be given the opportunity to wear the 
active study device for 8 weeks. These subjects will be evaluated once every 2 weeks during an 8-
week treatment period with the active study device (similar to the initial treatment period). 
For visual representation of the study design, see Section 2.2 Schedule of Events (SOE). 

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5.2. 
Scientific Rationale 
The study device was used in a pilot clinical trial (PPS-CTMD-15-001, 
ClinicalTrials.gov ID NCT02534493) that finished in October 2016 with promising results. 
Participants showed an average improvement in symptom severity scale (SSS) score of the Boston 
Carpal Tunnel Questionnaire (BCTQ) of 0.59 ± 0.68 points at 4 weeks (end of treatment period) 
compared to baseline SSS scores. After the 4-week treatment period, symptoms continued to 
improve for a total of 0.79 ± 0.74 points lower SSS compared to Baseline at 12 weeks.9 These 
results motivate the primary objective of this study. 
The pilot study investigated the effects of the study device up to 4 weeks, but the 
trajectory of SSS did not indicate that improvement plateaued by 4 weeks. Thus, the treatment 
period is extended to 8 weeks in this study to determine if improvements continue with longer-term 
wear. 
Analysis of the unilateral vs bilateral CTS patients showed a stark contrast in response. 
SSS of the unilateral patients improved 0.9 ± 0.5 points at 4 weeks and up to 1.2 ± 0.5 points at 12 
weeks. In contrast, the bilateral patients appeared to show no improvement; however, the pilot 
study was not powered to detect differences in unilateral and bilateral subgroups. This difference 
is being explored as an exploratory objective in this study. 
Most participants described the study device as being very comfortable and easy to 
wear. However, there were occasional comments about discomfort from the edges of the device. In 
Aim 1 of the NIBIB grant R44 EB024713-01, a series of experiments were conducted to investigate 
the applied pressures on wrists using tactile pressure sensors, the changes in median nerve 
dimensions using magnetic resonance imaging (MRI), and the changes in carpal tunnel or median 
nerve compression pressures in cadavers when the study device was applied to the wrist. This 
allowed the study device to be re-designed to fit a wider range of people and to reduce 
uncomfortable pressure points. A user feedback survey is incorporated in the present study to 
improve user satisfaction, which is critical for any practical application and success. 
 
6. 
STUDY POPULATION 
The study population includes adults ages 21 to 65 of all races and ethnicities and of both 
genders who meet the inclusion/exclusion criteria below. We expect to recruit at least twice as 
many women as men because studies have found that approximately 3 times as many women are 
affected by CTS as men.10,11 
6.1. 
Inclusion Criteria 
1. Ages 21-65 
2. Clinically diagnosed with mild to severe carpal tunnel syndrome (CTS) 
3. CTS diagnosis confirmed by a nerve conduction study (NCS) performed within the 
past 24 months OR at enrollment/baseline visit 
a. CTS severity determined via AANEM criteria13 
b. Bilateral CTS accepted (worse wrist via NCS and/or BCTQ is designated as the 
study wrist) 

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4. BCTQ SSS > 2 
5. Reliable access to and ability to use Internet, Wi-Fi, or mobile data through 
computers, mobile devices, laptops, and/or tablets 
6. Willing to abstain from any other treatment or therapies for CTS throughout the study 
7. Ability to read and write English, or has a reliable person to assist with reading and 
writing English 
6.2. 
Exclusion Criteria 
1. Other upper extremity neuropathies (e.g., epicondylitis, radial nerve neuropathies, 
ulnar nerve neuropathies) 
2. Double crush syndrome 
3. Cervical stenosis 
4. Brachial plexopathy 
5. Wrist fractures or cysts 
6. Prior wrist surgeries, especially carpal tunnel release surgery 
7. Injection of corticosteroid/cortisone into the wrist or hand within the past 6 months 
8. Thyroid disease 
9. Rheumatoid arthritis 
10. Diabetes 
11. Systemic diseases 
12. Connective tissue diseases 
13. Fibromyalgia or chronic pain syndrome 
14. Diabetic neuropathy 
15. BMI >40 
16. Participation in other research studies or clinical trials currently or within the past 2 
weeks. 
6.3. 
Prior/Concomitant Medications or Therapies 
1. No other therapies for carpal tunnel syndrome may be undertaken during the study 
(e.g., hand therapy, wearing wrist brace/splint, corticosteroid/cortisone injection to 
the wrist, carpal tunnel release surgery). 
2. Hand stretching exercises and stretches indicated for carpal tunnel syndrome are 
allowed. 
3. Yoga, tai chi, and other fitness programs often associated with helping with carpal 
tunnel syndrome are allowed but should be reported. 
4. No narcotics, opioids, or other prescription painkiller or pain medication may be 
taken during the study and must not have been taken for 3 months prior to 
enrollment. 
5. Over-the-counter low-dose NSAIDs or painkillers (e.g., Advil, Tylenol) are allowed 
if taken only as needed (e.g., to relieve pain caused by injuries, migraines, period 
cramps, menstrual pain) and taken no more than the recommended doses on the 
medication’s label (e.g., no more than 6 tablets in 24 hours). 
6. Pain creams should not be applied to the wrist where the device is applied. 

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6.4. 
Enrollment Determination 
Subjects that pass the inclusion/exclusion criteria, have provided or completed a NCS report 
confirming mild to severe CTS diagnosis, and have signed the Informed Consent Form (ICF) are 
considered enrolled in the study.  
6.5. 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical trial 
(i.e., sign the ICF) but are not subsequently randomized to a study intervention or enrolled. Some 
reasons for not enrolling after signing the ICF include the subject deciding not to participate or the 
discovery of disqualifying criteria after signing the ICF. 
In certain cases, a subject may need an NCS performed under their primary care 
provider after having signed the ICF. If the NCS report does not meet the inclusion criteria, the 
subject is not enrolled and is categorized as screen failure. 
6.6. 
Strategies for Recruitment & Retention 
Each site will advertise and recruit subjects per each site’s best practices and following 
applicable GCP, HIPAA, and all local to federal laws. Recruitment may be supplemented with 
IRB-approved physical advertisements such as flyers or cards and with IRB-approved digital 
advertisements on webpages and social media. Sponsor may supply advertising and marketing 
materials at Sponsor’s discretion or as needed by the sites.  
Sites may identify eligible subjects from their patient or volunteer databases or from 
their (electronic) medical records. Physicians at each site may identify eligible subjects during 
routine appointments, at which point the physician should offer information about the study to the 
patient. Sites may also obtain referrals from nearby or partner clinics. 
Before enrollment, all subjects are informed that there is a 50/50 chance of receiving 
the real device or the sham device. However, the sham group will be given the opportunity to 
undergo treatment with the real device upon completion of the main part of the trial (after Week 
12). This method seeks to increase fairness of participation and improve retention of sham group 
participants. 
 
7. 
STUDY PROCEDURES 
7.1. 
Screening, Informed Consent and HIPAA 
Subjects that pass the pre-screening questionnaire and meet all inclusion/exclusion 
criteria will be asked to participate in the study. The study design, objective, procedures, schedule, 
and participation parameters/criteria will be provided to and/or discussed with subjects prior to 
enrollment. Subjects wishing to participate must read and complete the Informed Consent Form 
(ICF) and sign an “Authorization for Use and Disclosure of Health Information for Research” 
release as a component of the ICF (HIPAA authorization) prior to undergoing any study-related 
procedures. 

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The ICF/HIPAA Authorization may be sent electronically to the subject. Subjects and 
designated site staff may sign electronically or can physically sign but must provide a scanned 
signed copy ICF/HIPAA Authorization to the site for documentation. 
Documentation of screening, eligibility confirmation, and reasons for ineligibility or 
non-participation will be kept in a Screening Log. 
 
7.2. 
Enrollment, Baseline Assessment, and Randomization 
7.2.1. 
Enrollment Procedures 
After the subject has passed the pre-screening questionnaire, the subject will begin 
enrollment, which includes reading and signing the ICF/HIPAA Authorization, completing 
the Enrollment Form which includes the BCTQ and NPRS, and confirmation of CTS 
diagnosis via NCS. After confirming meeting all inclusion/exclusion criteria, the subject is 
considered enrolled. The subject will be randomized into either the active device group or 
the sham group and assigned a Subject ID.  
Once the subject is enrolled, study devices are shipped (expedited) to the subject 
to begin treatment as soon after enrollment as possible. If a subject is bilateral, only the 
worse wrist (via NCS severity and/or SSS score) will be treated during the study. If NCS 
severity and/or SSS score are the same for both wrists, the dominant wrist will be treated. 
Standardized training and instructional materials will be provided to the subject on how to 
use the study devices, how and when to complete surveys, Diaries, etc.; how and when to 
report AE’s/SAE’s; and how to contact site staff or PI. 
7.2.2. 
Subject ID Assignment 
Subjects will be assigned a unique identification code (Subject ID). The subject ID 
is unique across all sites. After the subject is enrolled in the study, all forms will refer to 
the subject with the Subject ID and not the subject’s name. Each site will maintain an 
Enrollment Log linking identity of study subjects to the Subject IDs.  
7.2.3. 
Baseline Assessment 
The Enrollment CRF captures Baseline assessment measures. These include: 
● Date of birth/age 
● Gender  
● CTS severity (mild, moderate, or severe, from NCS) 
● CTS diagnosis by hand (unilateral/bilateral, right/left/both) 
● BCTQ and NPRS for affected hand(s) 
 
7.2.4. 
Randomization 
There are two treatment groups: active study device or sham device. Subjects will 
be equally randomized across all sites to ensure equal and equivalent active device and 

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sham groups. Randomization will occur using a Sponsor-supplied randomization tool or 
using the randomization module of the Electronic Data Capture (EDC) platform. 
 
7.3. 
Treatment Period 
The Treatment Period begins the first day that the subject begins wearing the device. 
Electronic Diaries are sent to subjects every day from the first day of treatment for 56 days. 
Subjects should be reminded if (s)he does not complete an entry. If 3 or more consecutive diary 
entries are missed, the site should contact the subject to remind them to complete entries or they 
could be withdrawn from the study. No more than 3 consecutive Diary entries and no more than 
25% of total entries should be missed (14 out of 56 diary entries), but withdrawal due to missed 
Diary entries will be up to Sponsor after evaluating the situation 
Follow-up surveys are electronically sent to subjects every 2 weeks from the subject’s first 
day of device wear up to 8 weeks. The subject should complete the surveys within 3 days and 
reminders should be sent if the subject does not complete the survey. If the subject does not 
complete the survey within 3 days, the site should follow up with the subject to remind them to 
complete the survey and address any issues preventing the subject from completing the survey. 
All subject correspondences and contact attempts should be documented. 
On the last day of treatment, the subject will complete a User Feedback Survey. This should 
be completed within 5 days. 
 
7.4. 
Post-Treatment Period (Active Study Device Group) 
After the 56th day of treatment (end of Week 8), subjects will stop wearing the device. A post-
treatment follow-up will then occur 4 weeks after the last day of treatment (Week 12). Survey 
completion and reminder timelines are the same as for the Treatment Period Follow-up Surveys 
above. 
Subjects in the treatment group will be exited after the last day of the Post-Treatment Period 
(end of Week 12) and after they have completed all required surveys and follow-ups. See Section 
7.6 Exit Procedures. 
7.5. 
Post-Treatment Period (Sham Device Group)  
After the 56th day of treatment (end of Week 8), subjects will stop wearing the device. A 
post-treatment follow-up will then occur 4 weeks after the last day of treatment (Week 12). The 
sham group will be offered the active study device at this point. If the subject agrees, then (s)he 
will wear the active study device daily for an additional 8 weeks and complete Follow-up 
Surveys biweekly and Diary entries daily. On the last day of treatment (Week 20), the subject 
will complete a User Feedback Survey. 
If the subject decides not to test of the active study device, then the subject will be Exited 
from the study. 

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7.6. 
Exit Procedures 
Exit procedures will only occur after the assigned site has ensured the subject has completed 
all required assessments and follow-ups. The assigned site staff member will complete the Exit 
CRF.  
An Exit CRF must be completed for any subject that has signed the ICF and is being 
withdrawn for any reason. 
7.7. 
Subject Withdrawal 
Potential reasons for withdrawal or removal of subjects are outlined below: 
● Subject decides it is in his/her best interest to withdraw 
● Principal investigator decides it is in the subject’s best interest to withdraw 
● Subject is noncompliant during the 12-week treatment period (i.e., Sponsor deems subject 
has missed too many Diary entries or Follow-ups). 
● Subject is lost-to-follow-up at any point (more than 5 documented attempts to contact and 
ask to complete follow-ups with no response after 3 weeks) 
● Subject fails to refrain from other CTS treatments or therapies. 
If the subject is withdrawn, the PI or designated staff member must fill out the Exit Form and 
document the reason for withdrawal or removal of the subject from the study. Unless the subject 
requests removal of their data, any data or information collected from the subject will remain in the 
database and analyzed at the sponsor’s discretion. 
 
8. 
Study Supplies 
8.1. 
Study Device Supply 
A designated Sponsor employee independent from the clinical trial will be delegated authority 
for shipping supplies to enrolled subjects (heretofore referred to as “Shipping Associate”). This 
individual will not reveal any PHI or PII to the other Sponsor employees involved in the clinical 
trial.  
Once a subject is enrolled, the Shipping Associate will be informed of the type of devices to 
ship (active device or sham), quantity, and the name and address to ship to. The Shipping Associate 
will expedite the package to the newly enrolled subject.  
If subject has not received devices by the expected delivery date, site staff must contact the 
Shipping Associate to re-send the package. Shipment and Confirmation Logs will be kept by the 
sites. 
8.2. 
Study Device Reconciliation and Destruction 
Subjects are asked to retain all used and unused study devices throughout the Treatment Period. 
At the end of the Treatment Period, or otherwise determined by the Sponsor, subjects will be asked 
to return all used and unused study devices by mailing the devices using supplied shipping 
materials.  
Number of lost, used, and unused devices will be reconciled for each subject. 

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The Sponsor will retain devices. Device destruction or disposition is at the discretion of the 
Sponsor.  
8.3. 
Other Study Supplies 
Study-related documents, investigator binders, study subject binders, and project trial binders 
will be provided by the sponsor. Other supplies will be supplied as needed and negotiated by site. 
 
 
9. 
SAFETY ASSESSMENTS 
9.1. 
Specification of and Methods for Collecting Safety Parameters  
Subjects will be able to report safety concerns on their surveys and Diaries. Subjects 
may also contact their assigned site staff directly with safety concerns. Subjects will be instructed 
to report any safety concern or medical event including injury, sickness, hospitalization or other 
adverse event that occurs during their involvement in the study.  
9.2. 
Adverse Events and Serious Adverse Events 
An adverse events (AE) is any unexpected medical problem experienced by the 
subject that occurs during treatment or during the study that may or may not be associated with 
the treatment.  
A serious adverse event (SAE) is any AE that results in a life-threatening situation, 
inpatient or prolonged hospitalization, significant incapacity or disruption of normal life 
functions, abnormal birth defect, or death. Any major medical event that may jeopardize the 
subject and may require medical or surgical intervention may be interpreted as SAEs. 
9.3. 
Reporting Procedures 
Site staff and Sponsor’s Clinical Research Manager will regularly monitor survey and 
Diary responses (e.g., daily for Diaries and as they come in for other surveys) for any safety 
concerns. Severity and relatedness of patient-reported safety concerns will be assessed by the PI or 
appropriately qualified site staff member. If determined to be the level of an adverse event or 
serious adverse event, the safety concern will be recorded in the AE/SAE Log within the IRB’s 
reporting timeframe. The PI or appropriately qualified site staff member will determine the 
necessary follow-up medical response.  
Minor AEs such as minor injuries (e.g., sprains, cuts, bruises) or minor illnesses (e.g., 
colds, flus, food poisoning) that are clearly not associated with device do not need to be reported 
to the Sponsor or IRB. AEs that result in injury to the affected wrist area or in discontinuation of 
device use should be reported to the Sponsor. 
SAEs are to be recorded as soon as possible from the discovery of the SAE and both 
the PI, sponsor, and IRB notified promptly. The Sponsor should notify all sites of an SAE. 
AEs/SAEs should be reported within the timeframes from IRB and GCP guidelines. 
9.4. 
Follow-up for Adverse Events 
Site staff should contact subjects that report an AE within 3 days of learning of the 
AE, unless the AE is minor (see above). 

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For subjects with a reported and recorded AE, site staff should contact the subject at 
each subsequent Follow-up (i.e., every 2 weeks during Treatment Period, every 4 weeks during 
Post-Treatment Period) to obtain an update on the status of the AE/SAE. The AEs should be 
followed until resolved, considered stable, or the subject is exited from the study. 
 
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Statistical Hypotheses 
10.1.1. 
Primary Efficacy Endpoint 
H0: Daily wear of the study device does not improve symptom severity. 
H1: Daily wear of the study device improves symptom severity by at least 0.4 
points. 
10.1.2. 
Secondary Efficacy Endpoint 
H0: Daily wear of the study device does not improve symptom severity in 
comparison to sham treatment. 
H1: Daily wear of the study device improves symptom severity by at least 0.4 
points more than the sham group. 
H0: Changes in symptom severity are not sustained after stopping treatment. 
H1: Changes in symptom severity are sustained or continue after stopping 
treatment. 
 
10.2. 
Sample Size Determination 
A total of 102 subjects are required for this study, with 51 in each group.  
The outcome measure used for calculations in the SSS of the BCTQ, which ranges 
from 1 to 5 with 1 being no symptoms (improved) and 5 being the worst symptoms (worsened). 
A moderate effect size of 0.4 was chosen, assuming that study device efficacy is 0.4 
greater than sham. 
The pilot study experienced a drop-out rate of 20% (2 out of 13 total). With the longer 
treatment and follow-up times of this study, a higher drop-out is expected.  Therefore the sample 
size calculation is modified by an estimated attrition rate of 25%.  
The primary objective examines the 8 week vs baseline within-active group SSS 
change. Sample size determination explanation. The power analysis using the above results in a 
significance level of 0.05 and a power of 0.94*. 
The secondary objective examines the change in SSS after 8 weeks between the active 
study device and sham groups. Sample size calculation is based on a parallel, one-sided t-test power 
analysis to identify an effect size of 0.4, standard deviation of 0.7 (based on the pilot study PPS-
CTMD-15-001), significance level of 0.05, power of 0.8, and an estimated attrition rate of 25%. 

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The sample size was chosen to meet both the primary and secondary objectives.  
10.3. 
Randomization and Blinding Procedures 
A simple randomization scheme is used to allocate subjects into the treatment group or 
the sham group. Site staff will be blinded to the randomization list and the Sponsor clinical research 
team blind to the allocation of each subject.  
Blinding will be broken for each sham group participant at his/her first post-treatment 
follow-up (Week 12) so that the site can offer the sham group participant the opportunity to try the 
active study device. Complete blinding will be broken at the end of the study when all data has 
been entered and validated and the database has been locked. 
Blinding may be broken if a subject experiences a SAE and if knowledge of the device 
is necessary for proper medical treatment of the SAE. Due to the low risk and minimal side effects 
associated with the device from previous studies, unblinding in most cases is not deemed necessary 
for medical treatment. 
The subject’s assigned site must obtain approval from the Sponsor to break the blind. 
After approval, the Shipping Associate responsible for randomization will provide the assignment 
for the subject in question. After a subject’s treatment has been revealed, this must be noted along 
with reasons for breaking the blind in the subject’s records and in the Deviation/Violation Log.  
10.4. 
Population for Analyses 
Statistical analyses will be based on a per protocol analysis - i.e., performed only on the SSS 
scores for subjects that have completed the full 8 week treatment period. 
10.5. 
Statistical Analyses 
The primary efficacy endpoint is the improvement (reduction) in SSS of the treatment 
group at 8 weeks after the first day of device wear. The primary efficacy endpoint will be analyzed 
using a paired, one-sided t-test. 
The secondary efficacy endpoint is the improvement (reduction) in SSS of the 
treatment group compared to the sham group at T4 (8 weeks after the first day of device wear). The 
secondary endpoint will be analyzed using a two sample one-sided t-test. 
A repeated measures analysis of variance will be used to evaluate changes over time 
in both the active and sham groups.  
The exploratory endpoints will be analyzed using descriptive methods. 
Safety analyses will be performed on all subjects that received treatment. 
 
11. 
DATA COLLECTION AND QUALITY ASSURANCE 
11.1. 
Data Collection Methods 
Data for each subject at each site will be entered into an electronic data capture (EDC) 
system. Paper forms used as CRFs, during enrollment, or at other time points will be entered into 

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the EDC by site staff. Surveys are administered to subjects to collect baseline, follow-up, AE/SAE, 
user feedback, and exit data. Subjects use their own devices to complete these surveys and Diaries 
online. Forms will record the subject’s ID, assigned site, date completed, and other relevant 
information. Subjects will be trained during or after enrollment on how to use and fill out these 
surveys. Support and re-training will be provided to subjects whenever requested. 
Appropriate security and privacy settings in the EDC system, or procedures set up for 
use with the EDC system, will be put in place to meet minimum applicable regulations. These may 
include audit trails, unique log-ins, and custom user access. The EDC system will be set up and 
managed by the sponsor’s Clinical Trials Manager or Clinical Trials Data Manager. Before study 
launch, the system will be tested and validated. 
11.2. 
Data Management 
The Sponsor Clinical Research (Data) Manager will control access to the EDC. 
Specific forms and functions will be granted to Sponsor and site staff based on their role in the 
study. The Clinical Research (Data) Manager will create the surveys and electronic workflow. 
Site staff and the Clinical Research Manager will have access to subject responses in 
the EDC and will have the ability to correct data when necessary. Data correction may occur in 
instances where a subject enters the wrong information (e.g., puts in 2018 for their birth year) and 
the correction has been verified.  
Once data collection is complete, the Clinical Research (Data) Manager will work with 
site staff to ensure accuracy and completeness of the data. Data will be exported, reviewed, cleaned 
as necessary, and then locked for statistical analysis. 
Unlocking of the database requires justification and approval. Reasons for unlocking, 
date of unlocking, and date of re-locking the database will be documented. 
11.3. 
Quality Assurance 
11.3.1. 
Training 
Training on the protocol, procedures, forms, and EDC system will be provided to 
the site prior to launch of the study. Training may be completed through teleconference 
or in-person, as determined between the Sponsor and the site. Training will be 
documented in Training logs. 
11.3.2. 
Deviations/Violations 
A deviation is an unplanned departure from protocol by the staff, participant, or 
investigator that does not cause significant consequences and is not intended to be a 
permanent or systematic change. 
A violation is a divergence from protocol that reduces the quality or 
completeness of the data (e.g., missing or erroneous critical information on the surveys, 
I/E criteria not met), makes the Informed Consent Form inaccurate (e.g., ICF not fully 
signed), or impacts a subject's safety, rights, or welfare (e.g., unreported SAEs). Other 
violations include repeated subject non-compliance and intentional departures from 
protocol. 

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Site staff and PIs should be vigilant in identifying, recording, and addressing all 
deviations from and violations of the protocol. All deviations and violations should be 
recorded in the Deviations/Violations Log. The PI or appropriately delegated individual 
will determine if the Sponsor and/or IRB should be notified. Any deviation or violation 
performed to protect patient safety or confidentiality or otherwise impacting patient 
safety or confidentiality should be immediately reported to the IRB and Sponsor.  
11.3.3. 
Monitoring 
A staff member(s) at each site will be responsible for regularly monitoring subject 
responses in the EDC system. If a subject misses Diary entries or survey responses beyond 
the acceptable windows, the designated site staff member will contact subject to ensure 
completion of the documents. 
The site staff member will also follow up with subjects to clarify entries that are 
or seem to be incorrect or questionable. 
The Sponsor Clinical Trials Manager or Data Manager will similarly monitor 
subject compliance and safety across all sites weekly or biweekly. Any errors, 
discrepancies, missed entries, or other entries of concern will be queried to the respective 
site. The clinical research coordinators (CRC) or similarly designated staff member at each 
site is expected to respond to and resolve or help the Manager resolve the issue in a timely 
manner. Queries and resolution will be tracked by the Clinical Trials Manager. 
The Clinical Trials Manager (or similarly designated staff member) will also check 
in regularly with each site to review items such as enrollment status, subject compliance 
and safety, supplies, and site questions or issues. These will be tracked in a Remote 
Monitoring Log. 
After the first 3 subjects are enrolled at each site, the Clinical Trials Manager or 
Associate will check in with the site to ensure procedures are being conducted as expected 
and to address any problems early on. If refresher training is needed, the site may request 
virtual in-person training with the Clinical Trials Manager. 
Interim monitoring visit(s) may be scheduled as needed. 
11.4. 
Study Data & Records Retention 
Study records will be maintained for at least 2 years after study close-out.  
 
12. 
PARTICIPANT RIGHTS AND CONFIDENTIALITY 
12.1. 
Institutional Review Board (IRB) 
This protocol and the informed consent document (provided as a separate document) and 
any subsequent modifications will be reviewed and approved by the IRB or ethics committee 
responsible for oversight of the study.  

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12.2. 
Informed Consent Forms 
The most recently approved version of the Informed Consent Form (ICF) will be used to 
obtain and document informed consent of study participants. The ICF is provided in English with 
no translations planned. If a new version of the ICF is approved during the study, previously 
consented and enrolled subjects will be re-consented using the newly approved ICF, only if the 
changes to the ICF are substantial and the IRB requires re-consent. 
A signed ICF will be obtained from each participant. For participants who cannot consent 
for themselves, such as those with a legal guardian, the guardian must sign the ICF. The ICF will 
describe the purpose of the study, the procedures involved, the requirements to follow, the risks and 
benefits of participation, and compensation. A copy will be given to each participant or legal 
guardian. 
12.3. 
Participant Confidentiality 
During screening, prospective subjects agree to provide their name, email, phone number, 
and potentially general area of residence (such as zip code, for assignment to closest research site). 
This information is used to email the prospect introductory study information and send study surveys 
and forms. To protect the privacy of enrolled subjects, no personally identifiable information will 
be included in any material sent to the Sponsor (except in cases listed below). This includes: 
enrollment logs, patient names, phone numbers, fax numbers, patient addresses, Social Security 
numbers, local hospital medical record number.  
The Sponsor employee responsible for shipping devices to enrolled subjects (“Shipping 
Associate”) will be not be involved in any other clinical research and will only receive the minimum 
necessary information to ship the correct devices to the subject (i.e., name, address, treatment).  
Compensation also requires that the name and address of the subject be provided to a 
Sponsor employee handling finances. In these cases, the name and address of the subject without 
the associated Subject ID will be sent to the designated employee to process and send compensation. 
The shipping and compensation employees will not be involved with any other component of the 
study and will not share any subject’s personally identifiable information with Sponsor employees 
associated with the study. 
 
13. 
PUBLICATION OF RESEARCH 
Authorship will reflect joint cooperation between PPS and participating PI(s). Authorship 
responsibilities should be established prior to the writing of any manuscript. 
No individual publications are allowed unless agreed upon, reviewed, and approved by the Sponsor 
before submission and/or publication. No individual publications are allowed prior to the completion of 
a final report for the study. 
 
 
 
 

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14. 
ABBREVIATIONS 
 
AE 
Adverse Event 
BCTQ 
Boston Carpal Tunnel Questionnaire 
CFR 
Code of Federal Regulations 
CRA 
Clinical research associate 
CRC 
Clinical research coordinator 
CRF 
Case report form 
CTR 
Carpal tunnel release 
CTS 
Carpal tunnel syndrome 
EDC 
Electronic data capture (usually followed by “system”) 
FDA 
(U.S.) Food and Drug Administration 
FSS 
Functional Severity Scale (of the BCTQ) 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form  
IRB/IEC 
Institutional Review Board / Independent Ethics Committee 
NCS 
Nerve conduction study 
NIBIB 
National Institute of Biomedical Imaging and Bioengineering 
NIH 
National Institute of Health 
NPRS 
Numeric Pain Rating Scale 
NSAID 
Non-steroidal anti-inflammatory drug 
PPS 
Pressure Profile Systems, Inc. (Sponsor)  
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SSS 
Symptom Severity Scale (of the BCTQ) 
Survey 
Various questionnaires completed by patients and used to collect study data (includes 
Follow-up and User Feedback Surveys) 
 
 
 
 
 
 
 

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15. 
REFERENCES 
1. Chammas M, Boretto J, Burmann LM, Ramos RM, dos Santos Neto FC, Silva JB. Carpal tunnel 
syndrome – Part I (anatomy, physiology, etiology and diagnosis). Rev Bras Ortop. 2014;49(5):429–
36. 
2. Dale AM, Harris-Adamson C, Rempel D, Gerr F, Hegmann K, Silverstein B, Burt S, Garg A, 
Kapellusch J, Merlino L, Thiese MS, Eisen EA, Evanoff B. Prevalence and incidence of carpal tunnel 
syndrome in US working populations: pooled analysis of six prospective studies. Scand J Work 
Environ Health. 2013;39(5):495–505. 
3. Hayward AC, Bradley MJ, Burke FD. Primary care referral protocol for carpal tunnel syndrome. 
Postgrad Med J. 2002;78:149-152. Published by group.bmj.com. 
4. Ibrahim I, Khan WS, Goddard N, Smitham P. Carpal tunnel syndrome: A review of the recent 
literature. The Open Orthopedics Journal. 2012;6(Suppl 1:M8):69-76. 
5. Chammas M, Boretto J, Burmann LM, Ramos RM, Neto FS, Silva JB. Síndrome do túnel do carpo – 
Parte II (tratamento). Rev Bras Ortop. 2014;49(5):437–45. 
6. Carlson H, Colbert A, Frydl J, Arnall E, Elliot M, Carlson N. Current options for nonsurgical 
management of carpal tunnel syndrome. Int J Clin Rheumtol. 2010;5(1):129–142. 
7. Walker WC, et al. Neutral wrist splinting in carpal tunnel syndrome: a comparison of night-only versus 
full-time wear instructions April 2000;81:424–9. 
8. Karl JW, Gancarczyk SM, Strauch RJ. Complications of Carpal Tunnel Release. Orthop Clin N Am. 
2016(47):425-433. Obtained from:  
http://www.orthopedic.theclinics.com/article/S0030-5898(15)00189-3/abstract.  
9. Luong PT, King FJ, Li Z-M, Dickason M, Diamond M, Son J. Pilot Clinical Study of a Novel 
Unobtrusive Carpal Tunnel Tissue Manipulation Device in Reducing Symptoms of Carpal Tunnel 
Syndrome. Poster presented at: American College of Rheumatology/Association of Rheumatology 
Health Professionals Annual Meeting, 2018 Nov 3-8; San Diego, CA. 
10. Ablove RH, Ablove TS. Prevalence of Carpal Tunnel Syndrome in Pregnant Women. Wisconsin 
Medical Journal. 2009;108(4):194-196. 
11. Stolp-Smith KA, Pascoe MK, Ogburn PL, Jr. Carpal Tunnel Syndrome in Pregnancy: Frequency, 
Severity, and Prognosis. Arch Phys Med Rehabil.1998;79:1285-1287. 
12. “Numeric Pain Rating Scale.” Physiopedia. Retrieved January 17, 2018, from https://www.physio-
pedia.com/Numeric_Pain_Rating_Scale. 
13. Leite JC de C, Jerosch-Herold C, Song F. A systematic review of the psychometric properties of the 
Boston Carpal Tunnel Questionnaire. BMC Musculoskeletal Disorders. 2006;7:78. doi:10.1186/1471-
2474-7-78. 
14. American Association of Electrodiagnostic Medicine, American Academy of Neurology, and American 
Academy of Physical Medicine and Rehabilitation. Practice Parameter for Electrodiagnostic Studies in 
Carpal Tunnel Syndrome: Summary Statement. Muscle Nerve. 2002;25:918–922.  
http://www.aanem.org/Practice/Guidelines-and-Performance-Measures. 
15. LeBlanc KE and Cestia W. Carpal Tunnel Syndrome. Am Fam Physician. 2011 Apr 15;83(8):952-8. 
 
 
 
 
 
 
 

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REVISION HISTORY 
VER # 
Effective Date 
Author 
Signature 
Notes 
3 
12/20/2018 
Pauline 
Luong 
 
1. Revised NCS time limit from 12 months to 24 
months 
2. Corrected minor date errors, flowchart errors 
3. Clarified blinding 
4. Clarified re-consent with new ICF versions 
2 
8/16/2018 
Pauline 
Luong 
 
5. Study design updated to minimize drop-out. 
Duration reduce to minimum needed for evaluation 
of Sponsor goals. Changes implemented under 
Synopsis, Schedule of Events & flowchart 
(including new SOE chart and flowchart to improve 
clarity), Study Design, Objectives & Endpoints, and 
Study Procedures.  
6. Replaced “COA” and “PRO” with the more 
accurate term “survey” 
7. Updated language regarding Survey and Diary 
completion requirements 
8. Corrected Daily Diary sent 56 days, not 28 days 
9. Included brief NCS explanation and associated 
Works Cited 
10. 
Updated example of withdrawal due to 
Sponsor’s evaluation of subject’s missing entries, 
rather than a flat number of missed entries. 
11. 
Updated that EDC system does not need to 
be 21 CFR Part 11 compliant but will be integrated 
within a system of processes to ensure minimum 
security  
1.1 
02/21/2018 
Pauline 
Luong 
 
12. 
Moved PROs from Appendix to separate 
documents 
13. 
Updated IFU and make separate document 
14. Added BCTQ as Appendix I (added reference). 
1.0 
02/05/2018 
Pauline 
Luong 
 
1st release 
 
 
 
 

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APPENDICES 
 
Appendix I: Boston Carpal Tunnel Questionnaire (BCTQ) 
Appendix II: Nerve Conduction Study (NCS) 
 
 

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APPENDIX I: BOSTON CARPAL TUNNEL QUESTIONNAIRE (BCTQ) 
The Boston Carpal Tunnel Questionnaire (BCTQ) is a patient-administered measure of symptom severity 
and functional impairment due to carpal tunnel syndrome. It has been shown to be “valid, reliable, 
responsive, and acceptable” tool to use as a primary outcome measure in carpal tunnel syndrome 
studies13.  
 
Each response has a value from 1 to 5. The average value of the responses to the first 11 questions 
provides the Symptom Severity Scale (SSS) score. The average value of the responses to the remaining 
7 questions provides the Functional Severity Scale (FSS) score. The lowest value is 1 and represents no 
symptoms or functional impairment. The highest value is 5 and represents the worst possible symptoms 
and functional impairment. 
 
Boston Carpal Tunnel Questionnaire (BCTQ)  
The BCTQ is 2-part survey that quantifies the severity of your carpal tunnel syndrome. Thinking about 
your symptoms due to carpal tunnel syndrome for a typical twenty-four (24) hour day during the past 
two (2) weeks, please answer the following questions. (If you have bilateral CTS (both hands affected), 
answer for the wrist that is more severe based on the nerve conduction study (NCS) results. If difficult to 
tell, answer for your dominant hand.) 
 
Part I - Symptom Severity Scale (SSS)  
  
1. How severe is the hand or wrist pain that you have at night? 
❏ I do not have hand or wrist pain at night 
❏ Mild pain 
❏ Moderate pain 
❏ Severe pain 
❏ Very severe pain 
 
2. How often did hand or wrist pain wake you up during a typical night in the past two 
weeks? 
❏ Never 
❏ Once 
❏ Two or three times 
❏ Four or five times 
❏ More than five times 
 
3. Do you typically have pain in your hand or wrist during the daytime? 
❏ I never have pain during the day 
❏ I have mild pain during the day 
❏ I have moderate pain during the day 
❏ I have severe pain during the day 
❏ I have very severe pain during the day 
 
4. How often do you have hand or wrist pain during the daytime? 
❏ Never 
❏ Once or twice a day 
❏ Three to five times a day 
❏ More than five times a day 

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❏ The pain is constant 
 
5. How long, on average, does an episode of pain last during the daytime? 
❏ I never get pain during the day 
❏ Less than 10 minutes 
❏ 10 to 60 minutes 
❏ Greater than 60 minutes 
❏ The pain is constant throughout the day 
 
6. Do you have numbness (loss of sensation) in your hand? 
❏ No 
❏ I have mild numbness 
❏ I have moderate numbness 
❏ I have severe numbness 
❏ I have very severe numbness 
 
7. Do you have weakness in your hand or wrist? 
❏ No weakness 
❏ Mild weakness 
❏ Moderate weakness 
❏ Severe weakness 
❏ Very severe weakness 
 
8. Do you have tingling sensations in your hand? 
❏ No tingling 
❏ Mild tingling 
❏ Moderate tingling 
❏ Severe tingling 
❏ Very severe tingling 
 
9. How severe is numbness (loss of sensation) or tingling at night? 
❏ I have no numbness or tingling at night 
❏ Mild 
❏ Moderate 
❏ Severe 
❏ Very severe 
 
10. How often did hand numbness or tingling wake you up during a typical night 
during the last two weeks? 
❏ Never 
❏ Once 
❏ Two or three times 
❏ Four or five times 
❏ More than five times 
 
 
11. Do you have difficulty with grasping and use of small objects such as keys or 
pens? 
❏ No difficulty 
❏ Mild difficulty 
❏ Moderate difficulty 

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❏ Severe difficulty 
❏ Very severe difficulty 
 
 
Part II - Functional Severity Scale (SSS)  
  
On a typical day during the past two weeks have hand and wrist symptoms caused you to have 
any difficulty doing the activities listed below?  Please circle one number that best describes 
your ability to do the activity. 
 
 
ACTIVITY 
 
 
No Difficulty 
 
Mild 
Difficulty 
 
Moderate 
Difficulty 
 
Severe 
Difficulty 
Cannot do at all 
due to hand or 
wrist symptoms 
Writing 
1 
2 
3 
4 
5 
Buttoning clothes 
1 
2 
3 
4 
5 
Holding a book 
while reading 
1 
2 
3 
4 
5 
Gripping a phone 
1 
2 
3 
4 
5 
Opening a jar 
1 
2 
3 
4 
5 
Household chores 
1 
2 
3 
4 
5 
Carrying grocery 
bags 
1 
2 
3 
4 
5 
Bathing and 
dressing 
1 
2 
3 
4 
5 
 
 
 
 

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APPENDIX II: NERVE CONDUCTION STUDY (NCS) 
An electrodiagnostic confirmation of carpal tunnel syndrome (CTS) in addition to clinical diagnosis of CTS 
is required for enrollment into the PPS-CTS-SBIR2 study.  A nerve conduction study (NCS) must be 
performed and provided to the site before patients can be enrolled into the study. The objective of the 
examination is to determine the presence of nerve damage or destruction in study subjects and to classify 
CTS severity as mild, moderate, or severe (per AANEM criteria13). The following NCS tests are the 
minimum tests that must be performed to confirm CTS diagnosis and provided for reference. 
 
Median and ulnar motor and sensory studies should have been performed on either (unilateral CTS) or 
both wrists (bilateral CTS) of each study subject to confirm CTS diagnosis. 
  
Procedure 
The study subject will be placed in a supine position and any clothing will be adjusted or removed to allow 
for exposure of the wrist and forearm.  Electrodiagnostic testing will be performed with a Cadwell Sierra 2 
EMG unit and a grounding pad will be used.  Skin temperature will be measured and testing will be 
performed with skin temperatures in the 26–32°C range. 
  
Four (4) separate sub-studies will be performed as part of the overall nerve conduction study 
(electrodiagnostic carpal tunnel testing) as follows: 
  
Median nerve sensory distal latency study: 
Orthodromic stimulation with active ring electrode placed at the base of the second finger and reference 
electrode placed distally 4 cm apart.  Stimulation is performed 13 cm proximal to the active ring electrode 
over the median nerve between the tendons of the palmaris longus and flexor carpi radialis. 
  
Normal values: 
Amplitude: > 20 µV 
Conduction velocity: > 50 m/sec 
Distal peak latency: < 3.5 msec 
  
Ulnar nerve sensory distal latency study: 
Ring electrodes are placed over the fifth digit 4 cm apart with the active electrode proximally at the base 
of the finger.  Stimulation is performed 14 cm proximally radial to the flexor carpi ulnaris.  Distal distance 
will be 11 cm. 
  
Normal values: 
Amplitude: > 17 µV 
Conduction velocity: > 50 m/sec 
Distal peak latency: < 3.1 msec 
  
Median nerve motor conduction velocity and latency study: 
The active surface electrode is placed one half the distance between the metacarpophalangeal joint and 
the thumb and the midpoint of the distal wrist crease.  The reference electrode is placed on the distal 
phalanx of the thumb. 
  

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Distal stimulation is performed 7 cm proximal to the active electrode over the median nerve between the 
tendons of the flexor carpi radialis and palmaris longus.  Proximal stimulation is performed over the 
medial aspect of the antecubital space between the biceps tendon and brachial artery. 
  
Normal values: 
Amplitude: > 4.0 mV 
Conduction velocity: > 49 m/sec 
Distal latency: < 4.4 msec 
  
Ulnar nerve motor conduction velocity and latency study: 
The active surface electrode is placed over the abductor digiti minimi on appointment between the distal 
wrist crease and the crease at the base of the fifth digit.  The reference electrode is placed on the fifth 
digit.  The elbow is flexed to 90°.  Stimulation is performed 8 cm proximal to the active electrode just over 
the flexor carpi ulnaris tendon; a second stimulation just distal to the ulnar groove and a third stimulation 
proximal to the ulnar groove, with the cathode distally placed. 
  
Normal values: 
Amplitude: > 6.0 mV 
Conduction velocity: > 49 m/sec 
Distal latency: < 3.3 msec 
  
All amplitude, conduction velocity and latency values will be recorded in the subject’s chart and results 
will be printed and attached to the subject’s chart. 
  
A one-sided (unilateral) nerve conduction study (electrodiagnostic carpal tunnel test) will take 
approximately 20 minutes to perform. 
  
In the case that diagnosis is still uncertain after performing these four sub-studies, the following two (2) 
sub-studies may be performed: 
  
Median/radial sensory study: 
Antidromic stimulation with the active ring electrode placed at the base of the thumb and reference 
electrode placed distally 4 cm apart.  Stimulation performed 10 cm proximal to the ring electrode over the 
radial nerve at the radial styloid process and over the median nerve at the wrist between the tendons of 
the flexor carpi radialis and palmaris longus. 
  
A difference of > 0.4 msec between the radial and median nerve peak latency, where the median nerve 
would be slower, will be considered abnormal. 
  
Median versus ulnar sensory latencies to digit 4 study: 
Ring electrodes are placed at the base of the 4th finger, active proximal, reference distal, 4 cm apart. 
Stimulation is performed over the medial and ulnar nerves at the wrist at identical distances from the 
proximal electrode (11-13 cm). 
  
A difference of > 0.5 msec will be considered significant.