Utilizing Platelet-Rich Plasma as an Adjuvant to Carpal Tunnel Release for Severe Carpal Tunnel Syndrome
Phase: NA
Conditions: Carpal Tunnel Syndrome, PRP
Sponsor: Michael Fredericson, MD

Utilizing Platelet-Rich Plasma as an Adjuvant to 
Carpal Tunnel Release for Severe Carpal 
Tunnel Syndrome 
NCT04811287 
February 28, 2023 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
This study assesses the potential benefit of adjuvant platelet-rich plasma (PRP) with 
carpal tunnel release (CTR) for patients with severe carpal tunnel syndrome (CTS). CTR 
is a rather common procedure performed and seems to be quite effective for those with 
moderate CTS, but a number of patients with severe CTS do not have quite the same 
response post-CTR. We will recruit patients who fall into the severe CTS category and 
compare CTR with and without adjuvant PRP to see if PRP can improve outcomes of this 
common surgery. 
b. 
Objectives 
Our primary aim of the project is to compare the post-CTR outcomes of patients with 
severe CTS with and without adjuvant PRP. We hypothesize that patients with severe 
CTS that undergo CTR with adjuvant PRP will have significantly improved Boston 
Carpal Tunnel Questionnaire (BCTQ) scores and grip strength in the long-term when 
compared to those with severe CTS that undergo CTR without adjuvant PRP. 
 
We hope that this study will provide evidence that PRP can be used as an effective 
adjuvant treatment for those with severe CTS that undergo CTR who have not 
traditionally had the best post-operative results. In particular, this will add to the field of 
evidence for PRP being used in nerve regeneration that is currently scant. This could 
open up doors for many other utilizations of PRP for peripheral nerve injuries within 
sports medicine. 
c. 
Rationale for Research in Humans 
The purpose of this study is to assess adjuvant PRP with CTR in patients with severe 
CTS. There are previous studies looking at the role of PRP in nerve regeneration at the 
basic science and animal model levels, but there are few-to-no studies that investigate it 
in humans. Human studies are thus required to assess this purpose. 

February 28, 2023 
 
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2. 
STUDY PROCEDURES 
a. 
Procedures 
1. Study team recruits patients with severe CTS who meet inclusion and exclusion criteria 
in an outpatient hand surgery clinic. Patient will be consented by the research team if they 
agree to participate in the research study. 
2. This will be a single blinded study, and participants will have an equal chance to be 
placed in either group. Participants will be randomized using permuted block 
randomization predetermined by our dedicated orthopedic biostatistician into two study 
groups: those that undergo CTR with adjuvant intra-operative PRP and those that 
undergo CTR without adjuvant PRP. All participants will have a pre-operative 
electromyography/nerve conduction study (EMG/NCS). 
3. Primary outcome measures (BCTQ and grip strength), and secondary outcome 
measures (PROMIS; 2 point discrimination - thumb, index finger and middle finger; key 
pinch; 3 finger pinch; and EMG/NCS results) will be collected and stored in REDCap at 
initial visit. BCTQ and PROMIS will actually be available online for patient to complete 
at his/her convenience. 
4. Patients will undergo CTR with or without adjuvant PRP (based on assigned study 
group). They will not know which group they are in (single blinded). 
5. BCTQ and PROMIS will be collected online at 3 months and 6 months post-
operatively. EMG/NCS will be performed pre-operatively, at 6 month post-operatively in 
the Sports Medicine clinic. At this visit, we will also collect data on 2 point 
discrimination, grip strength, key pinch, and 3 finger pinch. 
6. We will store data in REDCap. 
7. Data will be analyzed with the assistance of our biostatistician, and results will be 
written up. 
 
We will also be borrowing a centrifuge machine from Factor Medical, the company 
providing the Selphyl PRP kits. The machine will be used in conjunction with the PRP 
kits to derive the PRP. 
b. 
Procedure Risks 
The research procedures are optimized to be the least risky that can be performed with 
sound research design. CTR is a standard treatment for those with severe CTS, and 
numerous studies have looked into PRP as non- operative treatment for mild to moderate 
cases of CTS with some promising results and few negative side effects reported. Thus 
from previous studies, this investigation involves the least risky procedures while also 
advancing the science behind PRP. 
c. 
Use of Deception in the Study 
No deception will be used in the study. Patients will be notified of the two possible 
treatment groups they will be assigned to prior to consenting. 
d. 
Use of Audio and Video Recordings 
No audio or video recording will occur. 

February 28, 2023 
 
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e. 
Alternative Procedures or Courses of Treatment 
Alternative courses of treatment and procedures include conservative management with 
bracing, hand therapy, and steroid injections. However, once patients have reached the 
severe form of CTS that we are recruiting, standard treatment is CTR unless there is a 
surgical contraindication. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
Yes. Conclusion of this study does not preclude the patients from further treatment 
including repeat surgery in the future. 
g. 
Study Endpoint(s) 
We can analyze the data after each of the collection points during the study. However, 
since it will be continuous enrollment, each of the participants will be at different stages 
of the study procedure at any one time point. It would be reasonable to look at outcomes 
after half of the target sample size (aiming for 46 total participants) has had their 6 month 
post-operative data collected). If one treatment proves to be clearly more effective than 
the other during the course of the study (although this is unlikely given required statistical 
sample size), we could terminate the study prior to enrolling the projected total 
participant population. Otherwise the study will continue until we have reached our target 
sample size of 46 (23 in each group) that is based on our power calculation to achieve 
statistical significance. We approximate that the recruitment period will be about 3 years. 
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
CTS is the most common peripheral nerve entrapment and affects approximately 3% of 
the general population. Clinical symptoms include pain, numbness, tingling, and 
weakness in the hand innervated by the median nerve. Although CTS is a clinical 
diagnosis, EMG/NCS is traditionally used to categorize CTS into mild, moderate, and 
severe. Mild and moderate cases of CTS can often be treated with conservative measures 
including splinting, hand therapy, and steroid injections. Moderate cases that do not 
respond to conservative treatment as well as severe cases typically require surgical 
management with CTR. CTR seems to be quite effective for those with moderate CTS 
without axonal loss, but many of those with severe CTS with axonal loss on EMG/NCS 
do not necessarily respond well even after surgery. 
 
Over the past decade, regenerative medicine techniques have been increasingly utilized in 
the treatment of musculoskeletal disorders. PRP is one of the first and most studied 
regenerative medicine techniques. It activates cell proliferation by concentrating platelets 
and growth factors and creating an environment for healing. There have been some 
studies on utilizing PRP to promote nerve regeneration, but these have been primarily in 
the basic science and animal model realms. PRP has been studied in treating mild to 
moderate CTS non-operatively with promising results that suggest a role in nerve 
regeneration. Thus, PRP can be considered as a potential adjuvant treatment to CTR for 
severe cases of CTS that may otherwise not respond well to CTR alone. 

February 28, 2023 
 
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To date, there is only one study (by Trull-Ahuir et al. in Scientific Reports - Nature 
Research) that looked at this specific topic. However, our study will differ in numerous 
ways. First, we will have a control group (Trull-Ahuir et al. had compared PRP versus 
PPP). Also we plan to perform longer term follow-up up to 6 months. Our outcome 
measures will include more objective data such as repeat EMG/NCS. Additionally, we 
plan to focus on only those with severe CTS since it is the group that has a relatively poor 
prognosis even with surgical release. 
b. 
Findings from Past Animal Experiments 
There have been previous studies looking at PRP's effect in peripheral nerve regeneration 
in rat models (Kucuk et al. in Acta Orthop Traumatol Turc) and in rabbit models (Ikumi 
et al. in Microsurgery). Both studies demonstrated positive effects of PRP on nerve 
regeneration. This has led us to attempt to further investigate these positive effects in 
humans. 
4. 
RADIOISOTOPES OR RADIATION MACHINES 
N/A 
5. 
DEVICES USED IN THE STUDY 
a. 
Investigational Devices (Including Commercial Devices Used Off-Label) 
N/A 
b. 
IDE-Exempt Devices 
IND-Exempt Device 1 
Name: 
PRP Kit (Selphyl) 
Description: 
Platelet-Rich Plasma (PRP) Kit - Utilized to derive PRP from subject's 
own blood. 
 
6. 
DRUGS, BIOLOGICS, REAGENTS, OR CHEMICALS USED IN THE STUDY 
a. 
Investigational Drugs, Biologics, Reagents, or Chemicals 
N/A 
b. 
Commercial Drugs, Biologics, Reagents, or Chemicals 
Commercial Product 1 
Name: 
Platelet-Rich Plasma 
7. 
DISINFECTION PROCEDURES FOR MEDICAL EQUIPMENT USED ON BOTH HUMANS AND 
ANIMALS 
N/A 

February 28, 2023 
 
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8. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
(i) We expect to enroll 46 participants at the Stanford-affiliated site. 
(ii) Our study is single-site, so 46 will remain the expected total number of participants. 
(iii) Participants will all be adults aged 18 years and older seen in the outpatient hand 
surgery clinic who are diagnosed with severe CTS. 
b. 
Age, Gender, and Ethnic Background 
The participant population will consist of adults aged 18 years and older seen in the 
outpatient hand surgery clinic who are diagnosed with severe CTS based on EMG/NCS 
criteria. The participant population may have a small predominance of females over 
males as in previous studies, females have had a slightly greater incidence of CTS than 
males. Ethnic backgrounds of the participant population are currently unknown. 
c. 
Vulnerable Populations 
No potentially vulnerable subjects will be enrolled in our study. Women and minorities 
will be included, but treatment of their condition and participation in the study will not be 
predicated based on their volunteering in the study. All patients will receive the standard 
of care even if they do not participate in the study, and there are no financial incentives to 
persuade those who are economically disadvantaged to participate in the study. 
d. 
Rationale for Exclusion of Certain Populations 
Children are not included in the study as CTS is rarely found in this population. 
e. 
Stanford Populations 
We do not plan for there to be any study participants who are laboratory personnel, 
employees, and/or students. 
f. 
Healthy Volunteers 
There will not be any healthy volunteers as the inclusion criteria requires that the 
participants have severe CTS. 
g. 
Recruitment Details 
The study team will chart review EMG/NCS studies performed in the Sports Medicine 
clinic weekly and provide a list to the Hand Surgery providers of the patients that meet 
inclusion/exclusion criteria. In the Hand Surgery clinic, the patients will be provided 
information on the study and be consented if he/she decides to participate. 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
To be included in the study, participants must meet the following criteria: 
1. Adult age 18 years and up. 

February 28, 2023 
 
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2. Diagnosed with severe CTS based on EMG/NCS, meaning those with evidence of 
axonal loss (absent or low amplitude median sensory nerve action potential and/or 
absent or low amplitude median motor nerve action potential and/or evidence of 
abnormal spontaneous activity, reduced recruitment, or motor unit action potential 
changes on needle EMG of median innervated muscles). 
ii. 
Exclusion Criteria 
Study participants will be excluded if they meet the following criteria: 
1. Younger than age 18 years (minor status). 
2. Diagnosed with concomitant peripheral neuropathy. 
3. Previous CTR on the affected side. 
4. Have contraindications to PRP (platelet dysfunction syndrome, critical 
thrombocytopenia, hemodynamic instability, septicemia, local infection at site of 
procedure, consistent use of NSAIDs within 48 hours of procedure, steroid injection 
at treatment site within 1 month, systemic use of steroids within 2 weeks, tobacco 
use, recent fever or illness, or cancer). 
i. 
Screening Procedures 
1. All potential participants will have a pre-operative EMG/NCS performed. Based on the 
EMG/NCS results, the research team will speak to those patients who qualify during their 
normally scheduled office visit regarding their interest in participating in the study. 
2. The patients who volunteer to participate will be consented in clinic. If the patient 
would like some time after the office visit to think about it, the research team may 
consent the patient over email if the patient decides to proceed with the study. 
j. 
Participation in Multiple Protocols 
The first question on the consent form asks the participant if they are participating in any 
other research studies. We do not plan on having participants enrolled in multiple studies 
at the same time, and if they are already enrolled in another study, we will ensure that 
those study protocols would not affect ours prior to consenting. 
k. 
Payments to Participants 
Research participants will not be paid to participate in the study. All data will be 
collected during the typical office visits that patients who undergo CTR have even 
outside of this study. 
l. 
Costs to Participants 
PRP kits will be donated from a vendor, so there are no additional costs for the 
participants in the study. 
m. 
Planned Duration of the Study 
The duration of the entire study will likely be from 3/1/2021 to 2/28/2024. We anticipate 
that it will take approximately 3 years to recruit our desired sample size of 46 participants 
based on our power calculation to detect minimally clinically important differences in our 
primary outcome measures. Analysis of the data can be ongoing throughout the data 

February 28, 2023 
 
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collection process, but we should have all of our 6 month data by 2/28/2024. Then the 
data can be written up. 
(i) We estimate that screening of a participant should take about 5 minutes during the 
office visit. 
(ii) Subjects will be required to have additional visits in the Sports Medicine clinic at 6 
months post-op for quick repeat EMG/NCS's. Otherwise, there is no significant increased 
time in terms of active participation in the study for the patient. 
(iii) Analysis of participant data will take approximately 4 weeks following the 
completion of data collection. 
9. 
RISKS 
a. 
Potential Risks 
i. 
Investigational devices 
There are no investigational devices in this study. 
ii. 
Investigational drugs 
Not applicable. 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
There has been increasing evidence on PRP's use for musculoskeletal conditions, but the 
majority of the evidence is on knee osteoarthritis and chronic tendinopathies. Based on 
these previous studies, the primary risks include local infection (<1% chance) and pain at 
the site which are also risks of CTR alone. 
iv. 
Procedures 
Risks associated with the CTR include bleeding, local infection, increased pain, damage 
to the median nerve and/or surrounding structures, and risks associated with anesthesia. 
Major complications such as nerve damage occur in <1% of cases. Blood draws for the 
PRP also have risks of bleeding and infection but are very commonly done with rare 
complications. Risks associated with EMG/NCS include bleeding, local infection, and 
discomfort during the test. Bleeding and infection occur in <1% of tests performed. 
v. 
Radioisotopes/radiation-producing machines 
There are no radioisotopes/radiation-producing machines involved in this study. 
vi. 
Physical well-being 
The major risks to physical well-being for participants in the study involve those 
mentioned above associated with CTR, PRP, and EMG/NCS. 
vii. 
Psychological well-being 
There are no risks to the psychological well-being for participants in the study. 
viii. 
Economic well-being 

February 28, 2023 
 
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There are no direct risks to the participants' economic well-being as there are no 
additional costs to them during the study. 
ix. 
Social well-being 
There are no risks to the social well-being for participants in the the study. 
x. 
Overall evaluation of risk 
Low 
b. 
International Research Risk Procedures 
N/A 
c. 
Procedures to Minimize Risk 
All participants will be notified of potential risks of the study that, as outlined above, are 
primarily related to CTR and PRP. Patients will be followed longitudinally in one of the 
investigator's outpatient hand surgery clinic, and all adverse events will be recorded and 
monitored. To minimize risks to the confidentiality of identifiable information, 
participants will be assigned a study ID number, and all data will be stored securely in 
REDCap. Only the research team at Stanford will have access to the data. 
d. 
Study Conclusion 
The experiment will terminate for each patient following the 12 month follow-up visit. 
Those who decide to receive other interventions within these follow-up windows will 
have these interventions noted in our data. Necessary medical and professional 
intervention will be available through the clinic for adverse events as these will all be 
patients of one of the investigators. 
e. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 
Adverse events related to CTR with or without PRP as well as protocol deviations 
such as variation from post-operative standard of care will be reported and monitored 
throughout the study. 
ii. 
Person(s) responsible for Data and Safety Monitoring 
The protocol director and study team will be responsible for Data and Safety 
Monitoring for this study. 
iii. 
Frequency of DSMB meetings 
N/A 
iv. 
Specific triggers or stopping rules 
If there are 2 or more SAEs reported that are deemed related to the adjuvant PRP, this 
will trigger evaluation by the study team to determine whether it is safe to continue 

February 28, 2023 
 
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the study. Otherwise the study will end once the target sample size of 46 patients has 
been reached. 
v. 
DSMB Reporting 
The PD will disseminate the outcome of the reviews to the IRB and the study sponsor 
if reviews related to SAEs are required during the study. 
vi. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
Yes 
vii. 
Will a board, committee, or safety monitor be responsible for study monitoring? 
(Y/N) 
No 
f. 
Risks to Special Populations 
N/A 
10. 
BENEFITS 
Participants who are in the adjuvant PRP group may experience enhanced improvement in CTS 
symptoms if our hypothesis proves correct. In terms of the knowledge acquired from this study, 
we hope that this study will provide evidence that PRP can be used as an effective adjuvant 
treatment for those with severe CTS that undergo CTR who have traditionally had a relatively 
poor prognosis even with surgical release. This will add to the field of evidence for PRP being 
used in nerve regeneration that is currently scant and could open up doors for many other 
utilizations of PRP for peripheral nerve injuries within sports medicine. 
11. 
PRIVACY AND CONFIDENTIALITY 
Patient recruitment and consent will primarily be completed in person in clinic. In the cases 
where the patient decides to participate following their office visit and consent is obtained via 
email, we will utilize secure mail through Stanford and limit transmission of information to the 
consent form. 
 
PHI and HIPAA identifiers to be collected in this study include name, date of birth, gender, 
ethnicity, handedness, date of surgery, medical comorbidities, questionnaire results, EMG/NCS 
data, and physical exam data including grip strength and 2 point discrimination. 
 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, Stanford 
Health Care, and Stanford Children’s Health.