Evaluation of Objective Pain Measurement Device
Phase: NA
Conditions: Pain, Analgesia, Labor Pain
Sponsor: Stanford University

Evaluation of Objective Pain Measurement Device   
NCT03975660 
May 4, 2022 
 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
The aim of the study is to develop a device that can objectively measure pain. The study 
will attempt to objectively measure labor pain with an experimental device (CereVu 
ROPA). We will apply the device to determine if it is objectively able to measure patients 
reported pain due to uterine contractions before and after labor epidural analgesia. A 
brain oxygenation device, Edwards Foresight, will be used to concurrently to monitor 
brain oxygenation and hemodynamics, so the relationship between the CereVu ROPA 
device objective measure of pain and brain oxygenation/hemodynamic changes and 
patient-reported pain can be determined. 
b. 
Objectives 
The investigators hope to learn: If the pain measurement device (CereVu ROPA) is 
capable of reflecting different levels of pain ratings in patients in labor having uterine 
contractions and then changes in pain after receiving different neuraxial techniques for 
labor pain. Additionally determine the relationship between the CereVu ROPA device, 
brain oxygenation/hemodynamic changes and patient-reported pain scores. 
c. 
Rationale for Research in Humans 
The pain measurement device is intended to be used in humans. The study is using 
dynamic psychophysical testing, which necessitates the use of specific pain-related 
questions in order to get patients' feedback. 
2. 
STUDY PROCEDURES 
a. 
Procedures 
This study contains two phases. In phase 1 (device algorithm development) and phase 2 
(validating the device compared to your reported pain scores). Both phase will follow 
identical methods, only the data analysis is different.  Qualified subjects will be identified 
and contacted by the anesthesia team prior to their clinical evaluation for labor neuraxial 
analgesia. Potential patients will be informed of the study, and if they choose to 
participate, all to investigate be answered and an informed consent form will be signed 
prior to any study related activities. When they request labor analgesia, the area where the 
sensors of the pain measurement devices (CereVu ROPA and Edwards Foresight) will be 
applied to will be prepped with an alcohol swab. After allowing to dry, the sensors will 
be applied to the forehead on each side of the head and connected to the devices. Data 
recording is then started.  CereVu ROPA: Patients brain activity "objective pain" data 

May 4, 2022 
 
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will be obtained by the sensor and will be stored on a custom-built, radio shielded device 
that stores the data for further offline analysis along with patient-reported pain measures.  
Edwards Foresight device: Will be used to concurrently to monitor brain oxygenation and 
hemodynamics, so the relationship between the CereVu ROPA device objective measure 
of pain and brain oxygenation/hemodynamic changes and patient-reported pain can be 
determined.  After collection of baseline data for device algorithm development of up to 
70 patients, we will be moving to clinical validation study in which patients will receive 
our institution's standard labor epidural based on clinician preference (either epidural, 
dural puncture epidural or combined spinal epidural) to provide labor analgesia. Patients 
will undergo their standard medical and obstetric treatment at the discretion of the 
obstetrical and anesthesia team. There will be no delay in their treatment due to this 
study, and the device data will not be available of influence care. During the time of 
preparation of block, we will be obtaining baseline data. The research staff will be 
recording pain scores with contractions at regular intervals until approximately 45 
minutes after the epidural is placed and the patient is comfortable. 
b. 
Procedure Risks 
The above procedures pose minimal risk to the patients because the questionnaires should 
not cause any psychological or physical harm. There will be no change compared to 
standard treatment if the patient decides to participate in this study. The pain 
measurement will only be recording during standard clinical care. There will be no online 
display for "pain" on the device so potentially no change in medical treatment. 
c. 
Use of Deception in the Study 
No 
d. 
Use of Audio and Video Recordings 
No 
e. 
Alternative Procedures or Courses of Treatment 
The medical treatment will be the same for those patients involved in the study as for 
those in the general patient population. The alternative to participating in the study is not 
to participate. No standard treatments will be withheld in either case. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
NA 
g. 
Study Endpoint(s) 
Study end-point will be the completion of sample size. We will complete the enrollment 
and then do the data analysis. 

May 4, 2022 
 
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3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
Despite astonishing progress in our understanding of the basic mechanisms leading to the 
sensation of pain in the last few decades, the gold standard for measuring pain is still a 
subjective verbal numeric rating scale rating (0-10 or 0-100) obtained from the individual 
reporting pain. This is by no means objective, nor is it available whenever such a rating is 
warranted, for example from patients who are sedated or confused or anesthetized e.g. in 
intraoperative or intensive care settings. Pilot studies have shown promising correlations 
between subjective pain ratings and "pain" measured by similar pain measurement 
devices like the one we will use in this study. We, therefore, want to investigate the 
possible use of these objective pain devices in a clinical setting. 
b. 
Findings from Past Animal Experiments 
None 
4. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
This study will be done in two phases.  
i) In the validation study, 70 patients in labor will be recruited to get the baseline data.  
ii)Then in the clinical trial, we will be enrolling 60 patients to determine how the 
objective pain devices measurements correspond with the patient's reported pain score 
before and after labor epidural analgesia. The study population will be representative of 
the general laboring patient population receiving epidural analgesia (epidural, combined-
spinal epidural and dural puncture epidural as per clinician preference). 
b. 
Age, Gender, and Ethnic Background 
All ethnicities will be included. All females from 18 to 50 years will be included in the 
study. 
c. 
Vulnerable Populations 
The study will involve 130 pregnant women. Patients will be connected to the pain 
measurement devices via a sensor that will be applied to their forehead on each side. This 
carries a minimal risk of skin irritation. Patients will be monitored closely in the hospital 
per routine labor pain management. Analgesia will be provided by the obstetric 
anesthesia team per hospital routine, using all of the guidelines required to minimize risk. 
Every effort will be made to make sure subjects are comfortable while they complete the 
questionnaires. 
d. 
Rationale for Exclusion of Certain Populations 
Minors will not be included in this study. 

May 4, 2022 
 
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e. 
Stanford Populations 
These groups will not be targeted. If anyone from these groups will participate, they will 
be subject to the same inclusion/exclusion criteria, and provide the same written informed 
consent. 
f. 
Healthy Volunteers 
NA 
g. 
Recruitment Details 
In the LPCH labor and delivery, research personnel will first identify the patients suitable 
for the study by chart review and then they will be given information leaflets for the 
study. Research personnel will conduct all discussions about the study and answer any 
questions in a private manner. 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
1. Age 18-50 
2. ASA I-III +/-E 
3. Patient requesting epidural labor analgesia 
4. Good toco tracing (clearly showing contractions at least every 5 minutes) 
5. Pain score greater than or equal to 3 out of 10 with contractions 
ii. 
Exclusion Criteria 
1. History of chronic pain 
2. History of chronic opioid use 
3. BMI > 45 
4. Allergy to sensor adhesive material, local anesthetic or opioids 
5. Contraindication to neuraxial block 
6. Patient on magnesium infusion 
7. Inability to give informed consent 
8. Severe co-morbidities 
i. 
Screening Procedures 
Prospective subjects will be asked if they want to participate in this research study. If 
their answer is yes this will be documented on a Screening Questionnaire and they will be 
considered eligible to participate. Informed consent will then be obtained. 
j. 
Participation in Multiple Protocols 
Subjects will be asked if they are currently participating in other studies. If they are, each 
case will be evaluated separately to determine the potential for harm to subjects, or 
confounding study data. If it is determined that participating in more than one study at a 
time compromises either subject health or viability of the study data, subjects will not be 
enrolled. 

May 4, 2022 
 
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k. 
Payments to Participants 
There will be no payment for patients participating in this study. 
l. 
Costs to Participants 
There will be no charge to study subjects. 
m. 
Planned Duration of the Study 
The study is anticipated to take 1-1.5 years. 
The total time per participant will likely be: 
i) Patients requesting labor epidural will be screened. If interested, the study is described 
in more detail to them and written informed consent will be obtained. This screening 
process will take 10 minutes. 
ii) The period of active participation will be approximately 1 hour to obtain baseline data 
while setting up for the epidural (15 minutes), and then measure pain for 45 min after 
epidural placement. 
iii) Individual data analysis will take approximately 4 weeks. 
5. 
RISKS 
a. 
Potential Risks 
i. 
Investigational devices 
Patients will be connected to two objective pain measurement devices (CereVu ROPA 
and Edwards Foresight) via a sensor that will be applied to their forehead (one sensor on 
each side of their forehead). 
ii. 
Investigational drugs 
NA 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
NA 
iv. 
Procedures 
Non-investigational procedures include: 
1) Neuraxial blocks, risks of which may include (but are not limited to) injection pain, 
perivascular or inadvertent arterial injection with the risk of necrosis, postoperative 
nausea, and vomiting, nerve injury, post dural headache, rarely meningitis, compression 
of the spinal cord secondary to clot formation or abscess, paresthesia, and weakness. 
Patients will receive neuraxial analgesia as part of standard care and unrelated to this 
study. 
 
Study-related procedures include: 
1) Answering questions. This carries no risk. 
2) Applying a sensor with adhesive on the forehead of the patient. This carries a minimal 
risk of skin irritation. 

May 4, 2022 
 
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v. 
Radioisotopes/radiation-producing machines 
NA 
vi. 
Physical well-being 
Very mild risk of skin irritation due to sensor placement. 
vii. 
Psychological well-being 
No risks from study procedures. 
viii. 
Economic well-being 
No risks from study procedures. 
ix. 
Social well-being 
No risks from study procedures. 
x. 
Overall evaluation of risk 
Low 
b. 
International Research Risk Procedures 
NA 
c. 
Procedures to Minimize Risk 
Patients will be monitored closely in the hospital per routine labor pain management. 
Analgesia will be provided by the ob anesthesia team per hospital routine, using all of the 
guidelines required to minimize risk. Every effort will be made to make sure subjects are 
comfortable while they complete the questionnaires. 
d. 
Study Conclusion 
The experiment terminates after all data has been collected from the patients. 
Patients will be free to opt out of this study at any time. Patients will be able to contact 
any member of the research team in order to inform them about opting out. Patients can 
also opt out of the study by informing a member of the nursing staff. We will liaise with 
the nursing staff to ensure that the research team is informed if patients opt out by 
informing a member of the nursing staff. Once this is confirmed, no further patient or 
study data will be included in this study. A study investigator will confirm in writing that 
the patient has opted out of the study with relevant documentation in the patient's chart. 
We will ensure that our study does not detract from or interfere with any aspect of 
clinical management for each enrolled patient. If this occurs, study investigators will 
terminate the participation of individual participants in this study, and all data will be 
destroyed. 
e. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 

May 4, 2022 
 
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Initial data collection will occur at labor and delivery in LPCH. Patients will be asked 
to fill out the questionnaires. 
The sensors will then be applied to the forehead and the pain measurement device 
recording will be started. From this point on, the patient will receive the standard 
medical treatment as chosen by the anesthesia team. Any adverse event will be 
reviewed by research team. 
ii. 
Person(s) responsible for Data and Safety Monitoring 
The PD will monitor data and communicate if any concerns arise. This study is 
observing the usual standard of care with no interventions that could affect safety. 
iii. 
Frequency of DSMB meetings 
Data will be captured monthly. In case of any serious adverse event, the meeting can 
be called earlier too. 
iv. 
Specific triggers or stopping rules 
Patient discomfort will dictate if action is required. 
v. 
DSMB Reporting 
Outcome of the reviews by the ME will be communicated via secured e-mail. 
vi. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
Y 
vii. 
Will a board, committee, or safety monitor be responsible for study monitoring? 
(Y/N) 
N 
f. 
Risks to Special Populations 
NA 
6. 
BENEFITS 
There are no potential direct medical benefits for subjects participating in this research. Indirect 
benefits subjects may gain are a feeling of helping contribute to society, contributing to increased 
scientific knowledge, increased information about one’s own health or knowledge of resources, 
improvement in psychological well-being due to interacting with research staff or content of 
interviews/questionnaires. Potential benefits this research has to society is the ability to quantify 
pain objectively in subjects undergoing labor pains. It will also help to improve our knowledge of 
pain processing in patients undergoing different types of neuraxial blocks. 
7. 
PRIVACY AND CONFIDENTIALITY 
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.