Pain Relief Through Artificial Intelligence (AI) -Guided Dynamic Neuromodulation
Phase: NA
Conditions: Pain
Sponsor: Dandelion Science

 
Confidential. © 2021 Dandelion Science Corp 
Official Title: Digital Therapeutic for Pain Relief through AI-Guided Dynamic Visual 
Neuromodulation 
 
NCT Number: NCT06276881 
 
Document Date: December 21 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Confidential. © 2021 Dandelion Science Corp 
 
Digital Therapeutic for Pain Relief 
through AI-Guided Dynamic Visual 
Neuromodulation 
Version 1.1 / December 21 2021 
GOALS 
We are researching a novel neuromodulatory platform using visual stimulation for its impact on 
nociception. We hypothesize that short abstract videos can be optimized to be used in the 
modulation of nociception utilizing the process called Dynamic Visual Neuromodulation (DVN). 
DVN optimization will be performed through an iterative process of choosing different 
arrangements of concurrent stimulation parameters in order to enhance neurophysiological 
response. Since pain experiments are challenging, DVN optimization has been designed to be 
carried out in two stages in order to decrease the burden on participants: (1) In Experiment 1 we 
aim to develop an optimization procedure for inducing arousal; this experiment requires no pain 
induction. (2) Using the same general procedure, the Experiment 2 will pursue further 
optimization of the visual stimuli with the aim of inducing arousal to decrease nociception and 
the perception of experimentally induced pain in healthy subjects.    
OBJECTIVES 
The objective of the current research is to develop a visual stimulation platform capable of 
modulating nociception and alleviating perceived pain intensity. Dandelion Science (the 
Sponsor) hypothesizes that controlling the level of arousal through DVN can reduce nociceptive 
effects caused by experimentally produced painful stimuli in healthy participants.  
● Aim 1: Find dynamic visual stimuli capable of reliably modulating physiologic arousal.  
 
● Aim 2: Validate EEG, GSR, ECG, and EMG, biomarkers of pain. 

 
Confidential. © 2021 Dandelion Science Corp 
 
 
 
● Aim 3: Demonstrate that optimized DVN can modulate nociception and mitigate or 
modify pain perception in healthy participants*.  
 
 
 
 
BACKGROUND 
In 2017, 11 million of the 191 million prescriptions written for opioid pain medications were 
misused; 35% of opioid-related deaths (nearly 17,000 cases) were connected to these 
prescriptions (7 Staggering Statistics About America’s Opioid Epidemic, 2016). Researchers 
have been looking - with limited success (Nascimento et al., 2019) - for reliably safe and 
effective opioid-sparing therapies. The challenge is the complexity of pain (Murphy et al., 2017). 
Pain comes in many forms, is highly subjective (Fillingim, 2017; Krupić et al., 2019; Pisanu et 
al., 2019), and arises from complex neural data-processing across multiple regions of the brain 
(Fenton et al., 2015; Wiech, 2016). This complexity makes it challenging to deliver pain relief 
that is both safe and effective. Opioids offer efficacy but not safety. While clinical pain-relief 
interventions (e.g. cognitive behavioral therapy, CBT) and digital behavioral methods (e.g. 
guided meditation, distraction, and electronic CBT) are safe, none so far has been fully 
successful (Nascimento et al., 2019). 
 
 
The technology platform most 
compatible with this approach is neuromodulation, which makes use of direct, reproducible input 
- typically electrical or magnetic stimuli (Kumar & Rizvi, 2014) - and interacts with the CNS as 
a system of complex data-processing neural networks (Herculano-Houzel, 2009). 
 
 
Preliminary study data show that visual stimuli with certain dynamic features are able to induce 
neurologic and physiologic state changes. 

 
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INCLUSION AND EXCLUSION CRITERIA FOR THE EXPERIMENTS 
Participants will be recruited at the Dandelion Science’s lab 
The details 
pertaining to the recruitment procedures will be submitted in site-specific applications to the 
IRB. On the day of the experiment the participants will be encouraged to have a good night sleep 
and instructed to abstain from consuming caffeinated beverages and medical drugs. 
INCLUSION CRITERIA 
● Participants of both sexes 
● Participants of diverse ethnic and racial backgrounds 
● Subjects who speak, read, and understand English and are willing and able to provide 
written informed consent on an IRB-approved form prior to the initiation of any study 
procedures 
● Age range: 18-50 
The age limitation reflects differences in pain response thresholds both in terms of mean and 
variance, across different developmental groups (González-Roldán et al., 2020; Tumi et al., 
2017). Moreover, the age range stated above is the target group of individuals of greatest interest 
for this future intervention (Salmond & Allread, 2019).  
EXCLUSION CRITERIA 
A medical history questionnaire will be provided to determine which participants will need to be 
excluded.  
The following criteria will be used to exclude people from the study: 
● Patients with neurologic, endocrine, renal, gastrointestinal, and chronic pain disease 
● Participants who use unprescribed drugs or medications (a urine drug test will be 
administered on the day of the experiment to verify compliance) 
● Chronically medicated participants 
● Participants with photosensitivity and patients with epileptic seizures  
● Participants who have undergone major surgery within two months of the experiment date 
● Patients with cardiac disorders 
● Women who are pregnant  
● Prisoners 
● People who are unable to provide consent  
● Individuals diagnosed with a psychiatric disorder that is likely to interfere with the 
conduct of the study  
● Participants with implanted electronic devices of any kind, including pace-makers, 
electronic infusion pumps, stimulators, defibrillators or similar 

 
Confidential. © 2021 Dandelion Science Corp 
STUDY-WIDE NUMBER OF PARTICIPANTS 
Up to 120 participants 
STUDY-WIDE RECRUITMENT METHODS 
Participants for the study will be recruited by the Dandelion!s personnel using social networks 
and personal communications.   
STUDY TIMELINES 
 
Stages 
Au
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No
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Ja
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Fe
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Ma
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Apr Ma
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Jun Jul 
 
Recruitment  
 
 
 
 
 
 
 
 
 
 
 
Arousal optimization 
Experiment  
 
 
 
 
 
 
 
 
 
 
 
 
Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment  
 
 
 
 
 
 
 
 
 
 
 
Pain optimization 
Experiment  
 
 
 
 
 
 
 
 
 
 
 
 
Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY ENDPOINTS* 
Successful control of the arousal reduction of pain perception as measured by VAS and ERP for 
either thermal (CHEPs) or electric shock pain induction. While there is no single criterion for 
determining a clinically significant threshold, Dandelion Science has adopted the reported 
criterion of 20% reduction in pain intensity and expects to achieve a pain perception reduction of 
20% on VAS scale for AI-guided visual stimulation as compared with no-visual-stimulation in 
response to at least one of the nociceptive conditions (CHEPs stimulation). 
PROCEDURES INVOLVED 
The study consists of 2 experiments: 

 
Confidential. © 2021 Dandelion Science Corp 
Experiment 1. Optimization of visual stimulation for arousal  
In this experiment we will use the participant’s response to dynamic visual stimulation to modify 
and adapt the stimuli to drive a stronger arousal response. The goal is to show that visual 
stimulation can affect participants by both raising and lowering their arousal level. 
 
Location 
Dandelions Science Research Facilities 
Estimated number of participants 
Up to 100 
Estimated experiment duration 
2 hr 10 min 
 
Goals  
1. Identifying dynamic visual stimuli that are effective in manipulating arousal  
2. Developing and testing the platform: integration of neurophysiologic, behavioral and 
visual stimulation components 
Equipment and instruments 
1. Neurophysiologic assessment: EEG, GSR, EMG, ECG 
2. Behavioral assessment: self-assessment manikin (SAM)  
3. Visual stimulation: DVN presented on a  display 
4. Infrastructure: 2 laptops / PCs for rendering & processing of the data 
Conditions 
1. Optimized visual stimulation (OVS) 
2. Random visual stimulation control (RVS) 
Experiment structure 
Stages of experiment: 
1. Measuring temperature and a short COVID symptom questionnaire 
2. Signing of informed consent 
3. Urine drug test 
4. Filling out the demographic questionnaire (5 minutes) 
5. Filling out Perceived Stress Scale (Cohen, 1988) 
6. Sensor setup (~30 minutes) 
7. Sensor calibration (~5 minutes) 
8. Instructions (~2 minutes) 
9. Training block (~2.5 minutes) 
10. 25 Experimental blocks (~3 minutes per block). The blocks will be separated by breaks of 
45 seconds.  

 
Confidential. © 2021 Dandelion Science Corp 
Approximate trial and block structure 
 
1. Fixation cross - 1 second. 
2. Stimulation - 5 to 15 seconds total. 
3. Behavioral response - 5 to 15 seconds. 
 
 
Data Analysis 
Optimization method 
In the optimization procedure, Dandelion Science defines the visual stimulation (VS) parameters 
and, while they are presented, monitor the response to them. Once the response is registered, we 
select the next set of parameters that is expected to achieve one or more of the following goals: 
● identify and explore in detail VS parameters that affect a specific biomarker (i.e. that 
cause a significant shift in the biomarker in comparison with its baseline value); 
● find the specific values for VS parameters that drive a combination of biomarkers to a 
predefined state (“target state”); 
● improve our general predictive model of the relationship between VS parameters and 
bioresponse. 
Effectiveness of DVN in controlling arousal 
Dandelion Science will also collect the responses to randomly chosen parameters. This data will 
be used to estimate the quality of the signal and variance in responses and serve as a prior 
distribution for the Bayesian model. 
After we collect data for the baseline, we will compare the average response curve (a biomarker 
value for multiple participants over the course of random stimulation) with the response curve 
during the optimization procedure. We expect that after a few iterations, the biomarker values 
will diverge from the baseline. The required number of iterations to observe the effect is yet to be 
defined. 
We want to test whether optimization leads to the gradual improvement in the ability of 
stimulation to cause change in arousal as registered by the biomarkers. To do so we will analyze 
how the biomarker changed with control stimulation (RVS) versus optimized stimulation (OVS). 
The divergence of the time series will be calculated using the ARIMA model, and the 
significance of the diversion will be assessed using the Chow Test. 

 
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Pilot 
To assess the effectiveness of the optimization process, a baseline response will be collected to 
serve as a control condition. Prior to the main experiment we will run a pilot experiment on 5 to 
10 participants following the same structure as in the main experiment but with the visual 
stimulation parameters being chosen randomly during each iteration.   
In addition, up to 5 participants will take part in pilot experiments with the cold pressor test 
(Lamotte et al., 2021), a simple and validated test that has been used in clinical and research 
settings to evaluate non-baroreflex-mediated sympathetic neural control in humans. During the 
test the subject immerses one hand or foot into ice water for up to 3 min while blood pressure 
and heart rate are monitored.  
 
Experiment 2. Optimization of visual stimulation for pain perception 
 
 
In this experiment we will optimize visual stimulation with the goal of reducing pain perception. 
To reduce the burden on participants, optimization has been designed as a two-step process, with 
the first step (implemented in Experiment 1) requiring no pain induction. Our preliminary 
hypothesis is that arousal-inducing visual stimuli will reduce the perception of acute pain, based 
on the well-known phenomenon of stress-induced analgesia (Vachon-Presseau et al., 2013; 
Yilmaz et al., 2010). Thus, once we optimize the stimuli to affect arousal state in Experiment 1, 
we will test the effectiveness of the optimized visual stimuli (OVS) in reducing pain perception 
and carry out additional adjustments to further increase their impact.  
 
Location 
Dandelions Science Laboratory 
Estimated number of participants 
20 participants 
Estimated experiment duration 
2 hr 
 
Goals 
1. Find optimized visual stimuli  
2. Determine optimization curve 
3. Disentangle anxiety and pain responses 
Equipment and instruments 
1. Neurophysiological assessment: EEG, GSR, EMG, ECG 
2. Behavioral assessment: VAS 

 
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3. Visual stimulation: DVN presented on a display 
4. Infrastructure: 2 laptops / PCs for rendering & processing of the data 
5. Nociception: Contact Heat Evoked Potentials (CHEPs)  
Conditions 
Up to three pain intensities levels (cold: 3°C, innocuous: 35°C, hot: 52°C) with OVS. 
Experiment structure 
1. Measuring temperature and a short COVID symptom questionnaire 
2. Signing of informed consent 
3. Urine drug test 
4. Signing of informed consent 
5. Filling out the demographic questionnaire (5 minutes) 
6. Filling out Perceived Stress Scale (Cohen, 1988) 
7. Sensor setup (~30 minutes) 
8. Sensor calibration (~5 minutes) 
9. Instructions (~2 minutes) 
10. Validating pain levels using step method 
11. Training block (~2.5 minutes) 
12. 12 Experimental blocks (~4 minutes per block; 8 stimuli). The blocks will be separated 
by breaks of 45 seconds.  
Approximate trial structure 
1. Fixation cross 0.5 seconds 
2. Stimulation 0.5 - 15.5 (15 seconds total) 
3. Pain stimulation jitter window: 2 - 5 (pain stimulation of up to 800 ms can occur 
uniformly at any point within this window)  
4. Behavioral response window: 15.5 to 30 seconds. 
 
Block structure 
8 trials of 30 seconds = 4 minutes 
Data analysis 
Optimization method 
To facilitate the search for effective visual stimulation we will use a Bayesian model, pretrained 
on the data collected in Experiment 1.  
 
 

 
Confidential. © 2021 Dandelion Science Corp 
Description of the procedures used in the study 
Nociceptive protocols: Participants will be attached to the biosensors and seated in front of a 
digital display. Pain induction will be carried out as follows.  
 
 
1. Cold pressor Test: 
The cold pressor test is a simple and validated test in which the subject immerses one hand or 
foot into ice water for up to 3 min while blood pressure (BP) and heart rate are monitored. The 
cold stimulus activates afferent sensory pathways that, in turn, trigger a sympathetic response 
resulting in an increase in BP. The cold pressor test has been used in clinical and research 
settings to evaluate non-baroreflex-mediated sympathetic neural control in humans (Lamotte et 
al., 2021). 
 
2. Contact Heat Evoked Potentials (CHEPs): 
A contact heat stimulator will be employed to deliver stimulation (Pathway, Medoc, 
RamatYishai, Israel). The CHEPs thermode surface (diameter: 27 mm) consists of a heating 
thermo-foil covered with a layer of thermo-conductive plastic. The nominal heating rate of this 
device is 70 °C/ s, with a cooling rate of 40 °C/ s.  The temperature of the thermode will be 
controlled through dedicated software, designed for optimization purposes. The thermode was 
attached to the participant’s nondominant volar forearm. The stimulation will be conducted 
within the range of  40 °C for cold stimuli and 52 °C for hot stimuli. The duration of a single 
stimulation event will range from 800 ms to 10 seconds depending on the stimulation paradigm.  
Biochemical Test: 
1. 12 Panel Urine Drug Test Cup (Prime Screen ™ or a compatible alternative) 
 
Neurophysiologic measurements: 
1. EEG/ERP will be performed using a commercial active 32-electrode system (Biosemi). 
Before every session a participant will be fitted with a comfortable cap matching their 
head size. Conductance will be enhanced through the use of the standard EEG gel, which 
will be injected into the electrodes using plastic syringes with plastic tips. The 
experimental system will be powered by a low-voltage battery to avoid electrocution. 
2. GSR will be measured using a common commercial system ((Biosemi) using two 
electrodes and applying low voltage between them. The electrodes will be attached to the 
palm of the dominant hand. The device will be powered by a low-voltage battery. 

 
Confidential. © 2021 Dandelion Science Corp 
3. ECG will be measured by a common commercial system (Biosemi) consisting of one 
active electrode attached to the dominant hand. EMG will be measured by a common 
commercial system (Biosemi) consisting of two active pair of electrodes attached to 
participants face above right brow to measure corrugator activity and on the right cheek to 
measure zygomatic activity. Alternatively the electrodes may be placed on the 
participant’s dominant hand to measure arm muscles’ activity.    
Self-reports: 
1. Self-assessment manikin (SAM): 
Using a computerized questionnaire, participants will rate their subjective physiological 
arousal level by selecting one of the 5 figures representing decreasing levels of arousal (Bynion 
& Feldner, 2017; Handayani et al., 2015). 
 
2. Visual analogue scale (VAS)*: 
Participants will rate their experienced pain level on a standard computerized scale by 
choosing a point on a line (Ergin et al., 2015; Jamison et al., 2002). 
3. The Perceived Stress Scale (Cohen, 1988): 
A 14-item scale to measure general mental wellbeing (see attached).   
4. Demographic/situational questionnaire to access basic demographic information and 
compliance with the experimental requirements. 
 
 
Dynamic visual stimulation:  
DVN will consist of 15-second-long non-figurative dynamic visual patterns (see screenshot 
examples bellow):  
 

 
Confidential. © 2021 Dandelion Science Corp 
 
Screenshots from a visual stimulation clip.  
DATA AND SPECIMEN BANKING 
The personnel responsible for collecting and storing data will be specified in the site-specific 
protocols. The PI is responsible for all information collected on subjects enrolled in this study. 
All data collected during this study must be reviewed and verified for completeness and accuracy 
by the PI. PI will prepare and maintain adequate and accurate source documents designed to 
record all observations and other pertinent data for each subject participating in the study. In 
general data obtained from the participants will be recorded and stored in a HIPAA-compliant 
manner by a designated staff member. Subjects will not be identified by name in the study 
database or on any study documents to be collected by the Sponsor (or designee), but will be 
identified by a site number, subject number and initials. All questionnaire results will be coded as 
to the identity of the study participants in a HIPAA-compliant manner and therefore the study 
participants will not be identified with the recorded data. No such identifying information will be 
shared with anyone outside of the study sites. Obtained de-identified data will be used in 
secondary analyses. The consent form will include a request for secondary data utilization 
without an expiration date. All team members will be trained and certified in the HIPAA 
requirements for research involving human subjects.  
DATA MANAGEMENT 
Data obtained from the participants will be recorded and stored in a HIPAA-compliant manner. 
Specifically, the data will be de-identified and ID numbers assigned by the responsible 
investigator at the site will be used.  
Dandelion Science Corp intends to share the analysis results with the NIH and appropriate 
organization/entities that have oversight (e.g., IRB, safety officer). Any data that falls under the 

 
Confidential. © 2021 Dandelion Science Corp 
Dandelion Science Corp intellectual property will not be shared. Prior to any type of sharing, 
Dandelion Science Corp will de-identify and strip data of any information that can link the data 
with a particular participant. All the data will be stored and transferred in a HIPAA-compliant 
manner. The de-identified data may be shared in a HIPAA-compliant fashion with consultants 
and contractors who have a signed confidentiality agreement with Dandelion Science Corp.  
EEG data preprocessing:  
Cleaning EEG data involves removing artifacts from the EEG signal. Although the EEG system 
is designed to record neural activity, it also records electrical activity arising from physiological 
entities such as eye blinking or jaw clenching. The EEG will be digitized continuously at a 512 
Hz sampling rate. Data will be downsampled to 256 Hz and bandpass filtered using a 0.1 Hz 
high-pass cut-off (12db/octave) to reduce low-frequency noise such as drifting, and a 30 Hz low-
pass cut-off (24db/octave) to reduce high-frequency noise such as muscle tension. Following this 
step, data will then be re-referenced to the average of all channels. Then a time-frequency 
analysis will be performed to extract temporal dynamics of the major EEG wave bands (alpha, 
beta, theta and gamma). Signal processing will be performed using the MNE toolbox (Gramfort 
et al., 2013)and performed in Python. In addition, the painful stimulation-onset ERPs will be 
computed and the areas of N2 and P2 components will be used for the analysis. 
GSR data preprocessing:  
First, GSR artifacts will be detected by automatically identifying large, sharp changes in the 
amplitude, defined as an absolute value change of the derivative larger than 10. These artifacts 
will be corrected using cubic splines. Then the tonic and phasic components will be separated 
through FIR filtering. Then through application of a threshold a number of peaks will be 
calculated.  
ECG data preprocessing:  
The ECG data will be downsampled to 500 Hz. The QRS complex will be identified using 
Hilbert transform procedure and the R-R intervals will be computed.  
EMG data preprocessing: 
Analog band pass filter (20Hz to 500 Hz) will be applied to the raw signal before it is digitized. 
Then wavelet transform will be used to perform a time-frequency analysis on EMG data.  
 
Optimization training and testing*:  
During the optimization procedure, we will use alpha and beta EEG bands, number of peaks in 
GSR, heart-rate variability and facial EMG spectrum, among other features, to guide the arousal 
and pain-control optimization procedure. The success of the optimized stimuli in reducing pain 

 
Confidential. © 2021 Dandelion Science Corp 
perception will be evaluated using VAS. Prior data indicate that the minimal clinically relevant 
change in pain self-report should be 20%. In our study this effect will correspond to roughly an 8 
mm change on the 100mm VAS. If the true difference in the mean response of matched pairs is 8 
mm, we will need a sample of 30 participants to be able to reject the null hypothesis that the 
response difference is zero with a probability (power) of 0.8. The Type 1 error probability of this 
test is 0.05. 
PROVISIONS TO MONITOR THE DATA TO ENSURE THE 
SAFETY OF PARTICIPANTS 
The purpose of this study is to develop a novel treatment to help reduce pain through dynamic 
AI-guided visual stimuli. The Data and Safety Monitoring Plan (DSMP) outlined below for this 
Phase I grant proposal will adhere to the protocol approved by the IRB, as well as by all other 
committees that have oversight responsibilities for this research. Since the study entails only 
minimum risk to the participants, the PI will monitor the safety of the participants. The Study 
team members will compile data and report to PI, as well as to the funder.  
Our biosensor recordings have the potential to pick up abnormalities, including signs of focal 
and general epileptiform and non-epileptiform waveforms (EEG); arrhythmias, ischemia, and 
conduction abnormalities (ECG); and radicular abnormalities and metabolic-related conduction 
disorders (EMG).  
Adverse Events associated with Experiment 1 
Regarding the visual stimuli, adverse events are: 
• seizure, defined as jerking movements of the limbs and/or loss of consciousness, 
• dizziness/vertigo as defined by verbal complaints and loss of balance, and syncope. 
Adverse Events associated with Experiments 2  
We are concerned that pain induction and visual stimulation each has the potential for creating 
adverse effects, although they are unlikely to occur. CHEPs stimulation is commonly used pain-
induction models for experimental purposes. It has been well described and are known to have a 
very low potential for harm to study volunteers because the stimuli can be precisely controlled. 
Within the individually predetermined range of nociceptive stimulation, participants are expected 
to experience neither psychological distress nor tissue injury. The latter will be verified by study 
personnel through inspection of the involved skin after the first test stimuli are administered 
(during the initial demonstration of study procedures to participants) as well as after all 
nociceptive stimulation has concluded. Furthermore, the study team members involved in pain 
induction will be present throughout and observe the participants directly during the entire 
process. In the highly unlikely event of equipment malfunction or misapplication, both of which 

 
Confidential. © 2021 Dandelion Science Corp 
would trigger the need for reporting, arrangements will be made for participants to be evaluated 
by the on-site physician as stipulated in the protocol. 
With regard to pain stimuli, adverse events are: 
• excessive intensity of induced pain, defined as 80-100mm on VAS, 
• anxiety/fear, defined as a 100% increase (i.e., doubling) in heart rate or >135 beats per 
minute, and 
• injury to skin, likely in the form of a burn, defined as skin discoloration (i.e., red, white 
and/or brown) that does not resolve within 10 minutes of stimulus discontinuation. 
WITHDRAWAL OF PARTICIPANTS 
There are minimal risks to be incurred from participating in this study. Specific risks related to 
the clinical and cognitive assessments (study questionnaires), visual stimulation are described 
below.  
Participants will be reminded that they may stop participating in the study at any time for any 
reason with no penalty or loss of benefits to which they are otherwise entitled. Participants will 
be encouraged to take breaks when needed. They will be reminded that they may refuse to 
answer any questions on the study questionnaires, and they may stop the nociceptive stimulation 
session at any time.   
During arousal experiments, since the risk of adverse medical effect is extremely low and 
participants inclusion criterion bars participants with sensitivity to visual stimulation, any 
adverse effects will be dealt with through usual emergency procedures (calling 911).  
Syncope, vasovagal response, signs of seizure, and verbal complaints of dizziness and vertigo 
will be considered as criteria for terminating the experiment. The Project Coordinator on site will 
be responsible for reporting all events to the PI and Safety Officer within a day, and these events 
will then be reported to the NIH and IRB according to the following scheme: 
● Unanticipated problems, complaints and serious adverse events will be reported to 
NIH and IRB within 5 days 
● Unanticipated Adverse Device Events and Major deviations within 10 days. 
● Minor deviations will be aggregated and reported with continuing review or study 
closure.  

 
Confidential. © 2021 Dandelion Science Corp 
RISKS TO PARTICIPANTS* 
The potential risks of this experiment are extremely low. Given mild inconvenience of the 
CHEPs stimulation  we are excluding volunteers with cardiac, neurologic, endocrine, 
gastrointestinal or renal disease or chronic pain conditions, as well as those with a history of 
prior major surgery. In addition, the participants will be exposed to visual stimulation which 
could potentially induce seizures in individuals with heightened light sensitivity. Hence such 
participants will also be excluded from our study. 
 
POTENTIAL BENEFITS TO PARTICIPANTS 
There is no direct benefit of this research to the study participants. The potential benefit of the 
research is to society in general, through the future development of a safe, effective, and 
affordable treatment for pain. 
VULNERABLE POPULATIONS 
No vulnerable population is expected to participate in the study.  
MULTI-SITE RESEARCH 
The research will be conducted at the Dandelion Science research facilities in Hoboken, NJ.  
COMMUNITY-BASED PARTICIPATORY RESEARCH 
This type of research is not part of our experimental design 
SHARING OF RESULTS WITH PARTICIPANTS 
There is a potential for observing abnormalities in our biosensor recordings. For example, with 
EEG recordings, we can observe signs of focal and general epileptiform and non-epileptiform 
waveforms; with ECG, we can observe arrhythmias, ischemia, and conduction abnormalities; 
and with EMG, we can observe radicular abnormalities and/or metabolic-related conduction 
disorders. Given that records are not performed for diagnostic purposes, if abnormalities are 
suspected the participant will be informed that such an abnormality was observed and instructed 
to follow up with their health provider for further investigations. 

 
Confidential. © 2021 Dandelion Science Corp 
SETTING 
Dandelion Science facilities 
Laboratory 
Dandelion Science Corp 
 
 
 
Dandelion Science maintains its primary office at this location. At this location Dandelion 
Science maintains space for overall company management, as well as areas appropriate for 
computer research and computer programming activities. Dandelion Science maintains Internet 
access and wireless networking capabilities, computer workstations where software developers 
will be clustered together, beta testing rooms, conference rooms for privacy and larger meetings, 
video conferencing capabilities, as well as other standard office provisions. Dandelion Science 
will perform all programming and product development activities on secure company-owned 
computers. 
Scientific Advisory Board 
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Consultants 
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Dandelion Science Management Team 
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Confidential. © 2021 Dandelion Science Corp 
 
 
 
PRIOR APPROVALS 
The research will be funded through a NIH grant.  
CONFIDENTIALITY 
Participation in this research will be kept confidential. In compliance with HIPAA protocols, all 
presentations of data will be void of unique identifiers in order to ensure that participant 
confidentiality is maintained. The experiment preparation will be conducted in a dedicated room 
with only the participants, the experimenter and the assistants present. In the beginning of the 
experimental setup a participant will be requested to sign a consent form, in which the 
experimental procedures and their rights as participants will be explained. The participants will 
be asked to provide general demographic information consisting of their age, gender and 
race/ethnicity. During the setup the electrodes will be attached to the participant’s head, face, 
hands and palms, so participants will not be required to disrobe. The experiment will be 
conducted in a separate experimental booth, in which the participant will either be alone or with 
the experimenter depending on the specific details of the experiment.  
PROVISIONS TO PROTECT THE PRIVACY INTERESTS OF 
PARTICIPANTS 
The data will be collected and kept electronically on a computer hard drive. The hard drive will 
be password protected and will be kept in a locked secure facility. Upon completion of the 
experiment the data will be transferred to secure and encrypted online storage. All the 
information pertaining to the identity of the participant will be removed from the data used for 
analytical and presentation purposes. The demographic and other unique identifiers will be kept 
in a separate encrypted online storage. An assigned study number, saved with each participant’s 
unique identifiers and with study data, will be used to allow cross-referencing between separately 
stored information should there be a need to do so in the future. 

 
Confidential. © 2021 Dandelion Science Corp 
COMPENSATION FOR RESEARCH-RELATED INJURY 
 
In the event you become injured as a result of participation in this study, medical care will be 
available. The participants will be expected to pay for such treatment or seek reimbursement by 
their health insurance provider. Dandelion Science will cover the costs of reasonable and 
necessary treatment of study-related injuries that are not standard of care while the participants 
are in the study.  
ECONOMIC BURDEN TO PARTICIPANTS 
Participants’ economic burden should not exceed the costs involved in traveling to the study site 
and the opportunity costs of participation in the experiment, for which they will be compensated.  
CONSENT PROCESS 
All participants will be required to provide written informed consent for the planned research. 
Given that all participants are their own legal guardians, and no deception or blinding will occur 
in this research, it is expected that each participant will have full understanding of what they are 
agreeing to. As usual, participants will be informed that they can terminate participation at any 
time and for any reason, without negative repercussions and without having to state a reason. In 
addition, the participants will be provided with information regarding the funder of the study, the 
purpose of the study, expected length of participation, study procedures, participant 
responsibilities during the experiment, possible risks and discomforts, potential benefits from the 
research, and reimbursement of expenses (See attached the informed consent form).   
PROCESS TO DOCUMENT CONSENT IN WRITING 
The outcome of the consenting process will include written documentation to verify participant 
agreement required in writing. 
DEVICES* 
The pain stimulation devices will be used only by the authorized study team members and when 
not in use the equipment will be stored in the locked experimental booth. The OVS will be kept 
in the stimulation computer and will be assigned a participant id number. The access to the 
stimulation computer will be limited to the authorized study team members. 
Glossary 
 
CHEPs – Contact Heat Evoked Potentials 

 
Confidential. © 2021 Dandelion Science Corp 
DVN- Dynamic Visual Neuromodulation, general term for the neuromodulatory visual 
stimulation performed using Dandelion Science’s platform 
ECG - Electro-cardiogram 
EEG - Electroencephalogram 
EMG - Electro-myogram 
ERP - Event Related Potentials  
GSR - Galvanic Skin Response 
OVS - Optimized Visual Stimulation 
PI - Principal investigator 
RVS - Random Visual Stimulation  
SAM - Self Assessment Manikin (arousal and valence assessment) 
VAS - Visual Analogue Scale (pain assessment)"
 

 
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