Conditions: Healthy Adults
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 20
Healthy volunteers: yes

Brief summary:
Research shows that slow gentle skin stroking can activate special sensory nerves in the skin that elicit relaxing effects on the body and mind, similar to the effects of the hormone oxytocin. Studies also suggest that gentle stroking may even release oxytocin in the skin. However, we do not know what oxytocin does in the skin and how it affects nerves that send pleasant touch or pain signals to the brain. The proposed study will determine how individuals perceive gentle stroking and experimental pain before and after a skin injection of oxytocin compared to a placebo injection.

Detailed description:

Arms:
arm 1: Participants will receive 4mcg/2ml oxytocin during Session 1 and 2ml isotonic saline during Session 2, injected into the forearm. arm 2: Participants will receive 2ml isotonic saline during Session 1 and 4mcg/2ml oxytocin during Session 2, injected into the forearm.

Interventions: intervention 1: Pitocin
Intervention descriptions: intervention 1: At each session, 4mcg/2ml oxytocin or 2ml isotonic saline (0.9% sodium chloride; placebo control) will be injected into the middle of the dorsal forearm. Sessions will be separated by at least 48 hours to ensure drug clearance.

Protocol document:
Prot_SAP_000.pdf: 
Peripheral Oxytocin and Touch (POPP) 
 
NCT05326776 
 
Study Consent: 
 
Version date: 9/11/2023 


 
 
UCSD Human Research Protections Program 
New Biomedical Application 
RESEARCH PLAN 
Version date: 9/11/23 
1. 
PROJECT TITLE 
Effect of Peripheral Oxytocin on Touch Pleasantness and Pain 
2. 
PRINCIPAL INVESTIGATOR  
Dr. Laura Case, PhD, Assistant Professor, Department of Anesthesiology 
 
3. 
FACILITIES 
University of California San Diego (UCSD) Altman Clinical and Translational Research Institute (ACTRI) 9452 
Medical Center Drive, La Jolla, CA 92037 
4. 
ESTIMATED DURATION OF THE STUDY 
The proposed project will be ongoing for up to two years. 
 
5. 
LAY LANGUAGE SUMMARY OR SYNOPSIS (no more than one paragraph) 
Research shows that slow gentle skin stroking can activate special sensory nerves in the skin that elicit 
relaxing effects on the body and mind, similar to the effects of the hormone oxytocin. Studies also suggest that 
gentle stroking may even release oxytocin in the skin. However, we do not know what oxytocin does in the 
skin and how it affects nerves that send pleasant touch or pain signals to the brain. The proposed study will 
determine how individuals perceive gentle stroking and experimental pain before and after a skin injection of 
oxytocin compared to a placebo injection. This research will determine the role of oxytocin in affective touch 
and pain perception and whether it may have clinical potential to relieve pain. 
6. 
SPECIFIC AIMS 
 
Aim 1: Assess whether subcutaneous injection of oxytocin versus saline placebo has local anti-
nociceptive effects on experimental pain. 
 
Hypotheses: We hypothesize that OT will reduce pain threshold and ratings of pain intensity and 
unpleasantness for thermal, mechanical, and pressure pain.  
 
Aim 2. Assess whether subcutaneous injection of OT versus saline placebo alters local pleasantness 
of CT gentle stroking. 
 
Hypotheses: We hypothesize that OT will increase touch pleasantness of slow versus fast stroking and will 
increase heart rate variability.  
 
 
7. 
BACKGROUND AND SIGNIFICANCE 
Given the major burden of chronic pain in the U.S.1,2, there is an urgent need to understand basic mechanisms 
of chronic pain and develop effective interventions, including nonpharmacologic approaches like massage. 
While massage is widely sought for its effects of pleasant relaxation and pain reduction3, the neural 
mechanisms underlying affective touch and its effects on pain are poorly understood. A clear understanding of 
basic pathways for touch-based therapies is needed to understand the mechanisms of their effects on pain 
and mood, determine changes in chronic pain conditions, and identify potential targets for noninvasive 
modulation of affect and pain.  
 
Thickly myelinated Aα and Aβ afferent sensory fibers rapidly conduct proprioceptive and touch signals to the 
brain, while thinly myelinated Aδ and unmyelinated C-fibers transmit temperature, chemical, and pain signals 
at a slower speed34. A large body of evidence demonstrates that a subset of unmyelinated C-fibers known as 
C-tactile (CT) afferents project to the insula and convey the pleasant sensation of stroking on hairy skin4-7, 
leading to theories of a privileged CT pathway for affective touch4,8 as well as pain reduction9. As predicted by 
this model, patients with reduced C-fiber afference show reduced preference for slow stroking10, while patients 
with myelinated A-fiber deafferentation retain its pleasantness and insula response4. Furthermore, slow (CT-


 
 
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optimal) versus fast touch induces affective alterations including positive mood4,5 and increased heart rate 
variability6. 
Oxytocin (OT) is a neuropeptide broadly implicated in social behavior7. Systemic administration of OT reduces 
stress and anxiety and increases trust8. In addition, OT exerts antinociceptive and analgesic effects in both 
humans and rodent models9,10. Given the similar effects of CT stimulation and systemic OT, OT is a proposed 
mediator for the affective effects of CT touch11. Indeed, stimulation of sensory afferents induces OT 
release12,13, and intranasal OT increases touch pleasantness14. OT directly modulates wide dynamic range 
neurons in the spinal cord and C-fiber excitability15,16. These mechanisms may be engaged by social skin 
touch17, potentially mediated by keratinocytes17. Recent research in rodents demonstrates that OT also exerts 
powerful effects in the periphery, where OTRs on nociceptive terminal axons can inhibit nociceptive input.18 
Indeed, injection of OT into the paw reduced pain behavior in a neuropathic pain model, selectively in the 
injured paw19. Furthermore, in mice, OT injected in the ganglion reverses hypersensitization of HTMRs and 
hyperpolarization of LTMRs that is induced by nerve injury20. These studies demonstrate a local modulation of 
pain by peripheral OT. 
OT is not used clinically because it cannot penetrate the blood-brain barrier, has poor specificity and a short 
duration of effect, and cannot be patented21. However, only one study has tested the effect of peripheral OT in 
humans, demonstrating reduced postsurgical pain after subcutaneous OT injection prior to gallbladder 
surgery22. The OT group (N = 10) received subcutaneous OT (Oxitopisa, 4μg in 4ml of saline) in each of the 
surgical sites before surgical incisions were made. Pain was marginally reduced after surgery (Cohen’s d = 
3.53) and was significantly reduced upon discharge (Cohen’s d =4.16) and 24 hours after surgery (d =4.51)22. 
These effects have not been tested in healthy adults undergoing acute pain. These findings reveal a 
significant gap in our understanding of the role of peripheral oxytocin in the pathways for affective touch and 
pain. 
 
Effects of OT on pleasant touch have been tested through the intranasal route of administration. Chen and 
colleagues tested the effect of 24IU intranasal OT on 40 male subjects in a cross-over design administering 
positive, neutral, and negative valence touch on the arm with velocities targeting C-tactile afferents23. OT 
significantly increased touch pleasantness ratings independent of touch valence (estimated Cohens d = 3), 
with the effect largely driven by negative stimuli. This study provided the first evidence that OT may enhance 
rewarding effects of touch, regardless of valence. In addition, the same group administered manual or 
machine foot massage to 46 male participants. Intranasal OT significantly increased pleasantness ratings for 
manual massage, supporting the importance of OT for enhancing positive responses to social touch14. 
The proposed ACTRI pilot research project will identify the effect of subcutaneous oxytocin on experimental 
pain and pleasant CT stroking. This contribution will be significant as it will provide foundational knowledge 
about the role of peripheral OT in perception of affective touch and pain. This is important because 
pathological states alter affective touch perception29,31-33 and may involve corresponding changes in the role of 
peripheral OT in affective touch pathways, with potential significance for therapeutic use of peripheral OT. The 
central hypothesis is that OT will reduce pain threshold and ratings of pain intensity and unpleasantness for 
thermal, mechanical, and pressure pain. Further, we predict that OT will increase touch pleasantness of slow 
versus fast stroking and will increase heart rate variability. This research will advance our understanding of the 
mechanisms of touch-based therapies, such as massage, and identify potential targets for noninvasive 
modulation of affect and pain. 
8. 
PROGRESS REPORT 
None, this is an initial application. 
 
9. 
RESEARCH DESIGN AND METHODS 


 
 
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All procedures in this study are conducted solely for research purposes. 
 
This proposed study includes one baseline calibration session and two experimental testing sessions. To 
experimentally manipulate local OT in the skin, we will test the effects of subcutaneous injection of OT on the 
perception of acute pain and affective touch by comparing double-blind injection of 4mcg/2ml OT and isotonic 
saline placebo (2ml) on pain perception. 
 
Pre-Study Screening Procedures 
Interested individuals will complete the phone screening. This includes basic demographic and contact 
information as well as questions targeting medical inclusion and exclusion criteria (see Phone Screen 
Attachment). 
 
Consent 
Inclusion/exclusion criteria will be confirmed at the start of each session before consent is signed. Consent will 
be administered in-person in the ACTRI clinic at UCSD, at the beginning of Session 1. A member of the study 
team will discuss the consent form and answer any questions that may arise. 
 
Baseline measures: 
 
After consent is signed, basic demographic data will be confirmed from the phone screen record and logged in 
study records (name, date of birth, age, gender, sex at birth, ethnicity, race, telephone number, email address, 
current medications, and handedness). Current medications will be reviewed and updated at the beginning of 
each session.  Participants will be asked questions regarding their recent food, alcohol, and caffeine intake, 
smoking, exercise, and sleep to assess as study covariates. 
 
Study Questionnaires 
Participants will complete the following questionnaires in REDCap: 
• 
State-Trait Anxiety Inventory (STAI): This is a 40-item scale that measures both state and trait 
anxiety68. 
• 
Pain Anxiety Symptoms Scale (short form PASS-20): This is a 20-item scale that assesses fear in 
association with pain69,70.  
• 
Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2) [26]: This is a 37-item 
multidimensional instrument that includes 8 scales ranging from 3 to 7 items each.  The scales are 
noticing, not-distracting, not-worrying, attention regulation, emotional awareness, self-regulation, body 
listening, and trusting. 
• 
Body Awareness Questionnaire (BAQ): This 18-item scale measures attention to bodily processes72,73 
• 
The Autism Quotient (AQ): The AQ has been observed to negatively correlate with baseline OT 
concentrations23. 
• 
Adapted version of Longing for Interpersonal Touch Questionnaire: This questionnaire assesses touch 
received and desired in the last week. This questionnaire has been modified to remove gendered 
language. 
 
Heat pain calibration 
Ratings of heat stimuli will be collected to determine a moderately painful heat stimulus for use in pre- and 
post-sensory testing. Ascending and descending series of 10s heat stimuli (32-50C) will be presented on the 
arm until pain intensity is rated ‘70’ on the visual analog scale (VAS) pain intensity scale. 
 
 
Baseline measures will occur at the ACTRI and will take approximately 30 minutes to complete. 
 
Sessions 1 and 2/ Sensory testing with oxytocin or saline 
 


 
 
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Participants will be greeted and seated in a comfortable reclining position. 
 
Urine pregnancy test: Due to the risks of OT on a pregnancy, participants with the potential to become 
pregnant will undergo a urine pregnancy test at the beginning of both sessions. Participants with a positive 
pregnancy test will be dismissed. 
 
Baseline assays for peripheral oxytocin , inflammation, and metabolic features: Blood (approx. 10mL) 
will be collected from all participants at the beginning of Sessions 1 and 2 to conduct ELISA immunoassay to 
measure baseline OT concentrations, as well as baseline IL-6 (a pro-inflammatory cytokine) and metabolic 
features (approx. 20mL blood drawn total in study). 
 
Baseline heart monitoring: Participants will then undergo a 5-min baseline monitoring period during which 
resting heart rate will be monitored, using a Bionomadix wireless ECG system from Biopac (or equivalent). 
Heart rate will be continuously recorded in a time-locked manner throughout the session and used to calculate 
heart rate variability during affective touch and pain in either session. 
 
 
VAS measures: 
 
Participants will be asked to make the following ratings throughout the session: 
 
Intensity of the touch sensation: “No sensation” (far left) to “Most intense sensation imaginable” (far right) 
 
Unpleasantness of the touch sensation: “Extremely unpleasant” (far left) to “Neutral” (middle) to “Extremely 
pleasant” (far right) 
 
Pain intensity: “No pain” (far left) to “Most intense pain imaginable” (far right) 
 
Pain unpleasantness: “Extremely unpleasant” (far left) to “Neutral” (middle) to “Extremely pleasant” (far right) 
 
Skin monitoring: Photos will be taken of the participant’s arm before and after injection to document the 
possibility of any adverse response. Photos will not show any other part of the body other than the arm and 
will be deleted from the smartphone the same day as the session and stored on secure computers by subject 
ID, like our other PII. In the case of an adverse reaction, the study physicians will grade the severity of reaction 
as advised by the FDA. 
 
Pre-sensory testing 
 
Anxiety ratings will be collected using VAS rating scales for fear of pain (1 = “no fear of pain” to 100 = 
“extreme fear of pain”) and state anxiety (1 = “extremely calm” to 100 = “extremely anxious”) 
 
Affective touch perception: 
Affective touch testing will be comprised of 2 trials of 15s slow brushing and 2 trials of 15s fast brushing on 
each dorsal forearm, in a random order. After each trial participants will rate the (un)pleasantness and 
intensity of the sensation on VAS scales. 
 
Pain perception: 
Mechanical pain threshold (MPT): MPT will be determined using weighted pinprick stimuli exerting forces of 8, 
16, 32, 64, 128, 256 and 512 mN24. Stimuli will be applied for 2s on and 2s off until the first percept of 
sharpness (pain) is reported. 
 
Temporal summation: Temporal summation will be tested using a standard 256mN pinprick stimulus applied 
for 10 repetitions of 1s each, over the same 1cm² area24. The participant will provide pain ratings for a single 


 
 
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pinprick and for the 10 repetitions, using the VAS rating scales described above. This procedure will be 
repeated 3 times and the mean pain rating used. 
 
Pressure pain threshold (PPT): PPT will be tested using a pressure algometer placed over the dorsal forearm 
muscles (e.g. extensor digitorum), and pressure will be increased until pain is reported25. 
 
Heat pain threshold (HPT): HPT will be tested using a high-quality QST thermode. To establish HPT, the 
thermode will be placed on the arm at a baseline of skin temperature (automatically calibrated by the 
thermode) and will be increased until the stimulus is reported as painful by the participant24. The mean of three 
trials will be taken as the HPT. 
 
Heat pain ratings: Three 10s trials of the individually calibrated pain-70 heat stimulus will be rated using the 
VAS rating scales for pain intensity and (un)pleasantness described above. 
 
Injection of Oxytocin or saline control: Either 4mcg/2ml OT OR 2ml isotonic saline (0.9% sodium chloride; 
placebo control) will be injected into the middle of the dorsal forearm. Sessions will be separated by at least 48 
hours to ensure drug clearance19,26. Both participants and experimenters will be fully blinded with respect to 
OT versus saline placebo session/order. OT and saline will be prepared by the Investigational Drug Service at 
the ACTRI. OT will be prepared by diluting commercially available synthetic oxytocin (OXYTOCIN- oxytocin 
injection, solution from Fresenius Kabi USA, LLC or equivalent manufacturer supplied by the ACTRI research 
pharmacy; see uploaded package insert). The injection will be performed by a licensed healthcare provider. 
Saline placebo will be drawn from SODIUM CHLORIDE- sodium chloride injection, solution from B. Braun 
Medical Inc or equivalent manufacturer supplied by IDS pharmacy (see uploaded package insert). 
 
Blood pressure and oxygenation will be monitored before and after OT injection and at approximately 5 
minute intervals (BP) or continuously (pulse ox) for the remainder of the session. 
 
Post-sensory testing: Perception of pain and gentle brushing will be tested beginning ~10min after injection 
on the injected arm, given timing of OT effects in prior studies18-20, and then on the control arm. A post-block 
baseline sensory test will be conducted, identical to the affective sensory testing described above. All testing 
will be conducted within a ~3-4cm2 sized region of skin proximate to the injection site on the dorsal forearm. At 
the end of testing, the injected arm will be observed by a licensed provider to confirm normal sensation and 
lack of any adverse response to OT injection. 
Sessions 1 (after baseline) and 2 will occur at the ACTRI and will take approximately 1 hour each to 
complete. 
 
Participant Randomization: 
The schedule of randomization will be created and accessed by an ACTRI pharmacist only. Males and 
females will be randomized without replacement across a block of 20 codes (assuming 20% attrition) using an 
Excel-based random number generator. All subjects will receive OT in one session and saline placebo in the 
other in this within-subject cross-over study. Subjects will be randomized to one of two session orders 
(Session 1 OT and Session 2 saline; Session 1 saline and Session 2 OT). Randomization will be stratified so 
that each sex will have their respective list of randomization codes. Session order (blinded code) will be 
tracked in the Screening/Enrollment Log maintained by the study coordinator(s) and identity of the orders will 
be revealed by the pharmacy at the conclusion of the study. 
 
Blinding: 
This is a double-blinded study. The ACTRI nurses, research technicians, participants and investigators will be 
blinded to the study material until after the statistical analysis is performed. Subjects will be blinded to study 
material by being injected by the nurses. Oxytocin and saline are both clear fluids and will be administered in 
Identical syringes. The study coordinator will submit a prescription to the pharmacy for the correct session day. 


 
 
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Pharmacists will deliver the study drug in a blinded fashion, and the doctor or nurse will subsequently 
administer the study drug to the subject keeping the doctor/nurse, subject, coordinator, and research 
assistants blinded until trial completion. 
 
Timeline 
To ensure drug clearance, Sessions 1 and 2 (OT; saline placebo or saline placebo; OT) will be separated by 
more than two days according to the participant and experimenters’ availability19,26. After providing written 
consent (active enrollment), subjects will have 4 months to complete Sessions 1-2. Sessions will be offered to 
healthy volunteers until our sample size of 20 healthy volunteers has been reached. These sessions will be 
filled on a first-come-first-served basis. 
 
1-2 years will be required for recruitment, data collection, and analysis. 
 
 
Endpoints:  
Primary Endpoint: When all data for the primary and secondary outcomes are collected and statistical 
analyses of these data are complete.  
 
Outcome Measure(s) 
 
Primary Outcomes:  
• 
Pleasantness ratings of slow (primary) and fast gentle brushing 
• 
Pain perception assessed in response to noxious pinprick (primary), pressure, and heat stimulation. 
• 
Pain intensity and (un)pleasantness will be assessed with visual analog scales (VAS) as follows: pain 
intensity [anchors “no pain” (far left) to “most intense pain imaginable” (far right)] and (un)pleasantness 
[“extremely unpleasant” (far left) to “neutral” (middle) to “extremely pleasant” (far right)]. 100-point VAS 
scales are common, validated, and reliable measures of pain74,75,76. 
 
Key Secondary Outcomes: 
All questionnaires will be administered using the Research Electronic Data Capture (REDCap) platform 
facilitated by study personnel, before or during Session 1. They include the following: 
 
• 
State-Trait Anxiety Inventory (STAI; a measure of both state and trait anxiety68) 
• 
Pain Anxiety Symptoms Scale short form (PASS-20; an assessment of fear of pain69,70) 
• 
Multidimensional Assessment of Interoceptive Awareness (MAIA-271; a measure of interoceptive 
sensibility) 
• 
The Body Awareness Questionnaire (BAQ; a measure of attention to bodily processes72,73) 
• 
Autism Quotient (AQ27; observed to negatively correlate with baseline OT concentrations23). 
• 
.  
 
 
Sample Size Determination & Power 
We expect that pleasantness ratings of C-LTMR-optimal touch will be significantly increased after local OT 
injection and that pain perception will be reduced. In published studies, differences in postsurgical pain after 
local infiltration with OT versus control resulted in very large mean differences in VAS pain ratings of Cohen’s 
d = 3 to 4.5. In spinal nerve ligation (SNL) model rats, interplantar injection of OT versus control resulted in 
mean differences in paw withdrawal threshold of Cohen’s d =13.819. In addition, intranasal oxytocin (24IU) 
increases pleasantness of touch stimuli (especially driven by negative stimuli), with an estimated Cohen’s d of 
~323. Although these are very large effect sizes, accounting for sampling variability and differences in 
proposed study design (acute pain; healthy adults; subcutaneous OT administration), we powered the study to 
detect a large effect size of d = 0.8. Assuming a within-subject correlation of 0.5 and an attrition rate of 25%, 


 
 
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the proposed sample size of N = 20 will provide 0.8 power to detect an effect size as small as d = 0.8 based 
on a two-sided α = 0.05. 
Data Analyses and Interpretation 
General Statistical Approaches. Data will be analyzed descriptively and analytically. Descriptive statistics 
(means and standard deviations for continuous and proportions/counts for categorical outcomes) will be used 
to describe outcomes at baseline. Weighted generalized estimating equations (WGEE) will be employed, with 
appropriate link functions depending on the type of the response (e.g., identity for continuous and logit for 
binary outcome), to examine longitudinal changes in an outcome and longitudinal association between 
outcomes in regression analysis, controlling for covariates for Aims 1-2123. Unlike parametric models such as 
generalized linear mixed-effects models (GLMM), the semi-parametric WGEE requires no distribution 
assumption and yields valid inference for a broader class of data distribution under the missing at random 
mechanism123. WGEE provides valid inferences under the missing at random (MAR) mechanism124. We will 
use WGEE to test the missing completely at random (MCAR) assumption and will use the generalized 
estimating equations (GEE), if the MCAR is not rejected. GEE involves fewer parameters and provides more 
efficient inference than WGEE. Given the small sample size for Aims 1-2, we will complement the usual 
asymptotic inference with clustered bootstrap to improve inference validity and report the bootstrap inference if 
it differs from its asymptotic counterpart125. We set α=0.05 for all analyses and use Holm-Bonferroni 
adjustments for <= 5 tests126 and False Discovery Rate (FDR) for > 5 tests127. When correlated outcomes are 
analyzed (e.g., outcomes in related domains), corrections will be calculated based on the effective number of 
independent tests that account for correlations between the outcomes128. Whenever possible, effect size will 
be reported in addition to point and interval estimates. All analyses will be performed using the latest versions 
of R129 and SAS130. Hypothesis Testing. For Aim 1, separately for OT and saline placebo sessions, we will 
compare changes in ratings of pain over time between the OT and control arm using WGEE, where time (one 
binary indicator) will be the predictor, controlling for covariates. A significant time effect, tested using 
appropriate linear contrasts, will support the hypothesis that the OT injection has effects on the outcome. We 
will follow with post hoc analyses to estimate the effect size of the OT injection. For Aim 2, we will apply the 
same approach in Aim 1 to pleasant touch outcome. Age and race/ethnicity will be included as potential 
covariates in all analyses. 
 
10. HUMAN SUBJECTS 
 
Subject Population 
A total of 20 healthy adults, ages 18-65, will complete two separate test sessions in a within-subject crossover 
study. Equal numbers of males and females will be recruited. Data will be analyzed to determine if sex is a 
significant predictor of study outcomes. We will include all genders, races, and ethnicities. 
 
Inclusion Criteria: 
All participants will be: 
1) Between the ages of 18 and 65 years old 
2) Fluent in English 
3) Healthy 
 
Exclusion Criteria:  
4) Body-mass index under 20 
5) Sensory or motor nerve deficit 
6) Acute or chronic pain 
7) Major medical conditions such as kidney, liver, cardiovascular (hypertension, preexisting cardiac 
arrhythmia), autonomic, pulmonary, or neurological problems (e.g., seizure disorder) or a chronic 
systemic disease (e.g., diabetes). 
8) Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal 
Investigator, would place the subject at increased risk (active gynecologic disease in which increased 


 
 
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tone would be detrimental e.g., uterine fibroids with ongoing bleeding), compromise the subject’s 
compliance with study procedures, or compromise the quality of the data 
9) Unstable psychiatric conditions 
10) Needle phobia, needle-related anxiety, or history of fainting from needles 
11) Current use of opiate medication(s) 
12) Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin® 
13) Currently pregnant or pregnant within the last two years  
14) Currently nursing or lactating 
15) Current or history of ventricular tachycardia, atrial fibrillation or prolonged QT interval 
16)  Past or current history of hyponatremia or at risk for hyponatremia 
17) Current use of pseudoephedrine, thiazide diuretics, loop diuretics, combination diuretics, lithium, 
carbamazepine, enalapril, Ramipril, celecoxib, temazepam, gliclazide, glimepiride, glibenclamide, 
glipizide, omeprazole, pantoprazole, desmopressin, SSRI’s, MAOI, or the recreational drug ecstasy 
18)  Latex allergy  
 
Participants will be asked to avoid drinking alcohol for at least 48 hours prior to study sessions, avoid over-the-
counter pain medications and other over-the-counter medications, including allergy medications for 24 hours, 
avoid exercise, or drinking more than 1 caffeinated drink for 24hrs, and avoid nicotine andcaffeinefor 2hrs 
before study sessions. We will collect information about these behaviors at each study session to include as 
study covariates but will not exclude for these additional behaviors. There will be no other restrictions on 
medication(s) during this study. They will be permitted to use any supplements, complementary and 
alternative therapies, treatments, and/or procedures for medical purposes during the course of this study. 
 
11. RECRUITMENT AND PROCEDURES PREPARATORY TO RESEARCH 
 
Subjects will be recruited through three primary streams: (1) from IRB approved flyers and ads posted in the 
San Diego area, 2) the ResearchMatch website and 3) from past studies at UCSD. We will begin study 
recruitment after we have completed all NIH oversight requirements.  
 
1) We may post IRB approved flyers throughout the community. 
 
2) The study may be advertised on ResearchMatch to gain interest for participation. This site will allow for 
members of the community to inquire as to their potential interests in the study’s goals and 
requirements.  
 
3) The study may be advertised to participants from our lab’s past studies at UCSD.  
 
We will not directly contact or call the patient unless the patient, themselves, contacts the study team first 
through contact information provided on study advertisements or the patient’s treating physician refers them to 
the study. When a potential subject contacts our lab, a brief subset of preliminary eligibility criteria (such as 
age, gender, etc.), will be reviewed by study personnel to determine subjects’ preliminary eligibility for the 
research study during the phone screening. The attached phone script will be employed to identify preliminary 
study eligibility. The study team member screening potential subjects will obtain verbal consent before any 
subject information is collected. Subjects who fulfill the preliminary eligibility criteria will be offered further 
participation in this study. 
 
Preliminary eligibility may be determined at the time of phone screening, but formal eligibility will only be 
determined directly before informed consent is obtained when screening criteria are readministered reviewed. 
If a subject qualifies for the study, information collected from the phone screens will be entered into two 
separate password-protected databases: one for personal identifiable information, and one containing the 
participant’s responses. In the second database, the subject will be identified with a recruitment number that is 
determined simply by the order in which subjects contact us. This second database, linking participants’ 


 
 
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personal identities to code numbers will be stored in locked research files separately from research records. 
Only subjects who have consented will have identifiers or linked information (e.g., subjects initials, study 
numbers, etc.) recorded on the Screening/Enrollment Log. The Screening/Enrollment Log is necessary to 
keep track of who the subjects enrolled in the study are, and record their responses to the screening questions 
for use in describing the study sample in any resulting publications. No entries will be made in the 
Screening/Enrollment Log for individuals who do not pass screening or do not consent. Thus, the hard copy 
Phone Screen will be shredded immediately for subjects who do not qualify, and after the information has 
been entered into our password-protected databases for subjects who do qualify (after written consent is 
obtained). The Phone Screen (excluding the page with contact information) will be labeled with the recruitment 
number, which will also be used to link the two databases. Hard copies of screening responses will be labeled 
only with the date and the participant recruitment number. The study funder (NIH) will not have access to the 
subject’s PHI.  Only team members, as described in item 21, will have access to this information.  
 
Recruitment materials that are not included in this submission (such as researchmatch ad) will be submitted to 
and approved by the IRB prior to use. 
 
12. INFORMED CONSENT 
 
Consenting Procedures: 
Once a potential study participant expresses interest in our study and meets preliminary eligibility 
requirements, as determined by phone screening, the subject will be asked to provide written consent, using 
an IRB-approved consent form during their first study session. The consent process will take place prior to 
performing any study related procedures and in a private room with the door closed. The study team member 
will describe the study, including detailed information about risks and benefits, to potential subjects. The study 
team member will provide potential subjects with an IRB-approved consent form. Potential subjects will be 
given ample time to read this consent form at the same visit or may take it with them to read at another time. 
Potential study subjects will be given the opportunity to ask and receive answers to all questions they may 
have about the study, its risks and benefits, or the consent form itself before signing the consent form.  As this 
research is subject to HIPAA privacy rule provisions, subjects will also be requested to sign a separate HIPAA 
authorization for the use of protected health information.   
 
Questions will be asked and elicited in order to ascertain that participants comprehend the study procedures 
as well as potential risks involved, prior to consenting to the study. All study related questions from study 
participants that a research staff member is unable to address will be referred to the Principal Investigator, or 
other co-investigators. No clinical information beyond screening (extended phone screen and clinical 
information) will be gathered until participants have provided written, signed informed consent. 
 
Potential subjects who fulfill the eligibility criteria will be offered further participation in this study.  Only 
subjects who have consented and provided HIPAA authorization will have identifiers or linked information 
(e.g., subjects initials, study numbers, etc.) recorded on the Screening/Enrollment Log. 
 
All signed consents will be maintained on laboratory password protected computers and servers, as well as in 
marked binders secured in locked filing cabinets within private offices or cubicles in Dr. Case or Dr. Zeidan’s 
laboratories in the ACTRI. Documentation of this process will be written form and placed in the research 
record. A copy has been uploaded for IRB review and approval. 
 
13. ALTERNATIVES TO STUDY PARTICIPATION 
The alternative to participation in this study is not to participate. 
 
14. POTENTIAL RISKS 
This study may involve some risk, although the risks are considered minimal.  
 


 
 
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Risks for screening and questionnaires: 
We have included a number of validated questionnaires to assess variations across individuals. Some of these 
items include sensitive questions about one’s psychological and health state.   
 
Risks for heart rate recording (ECG): 
The ECG procedure may cause some mild discomfort during the placement and removal of the leads to and 
from the skin. You may also experience some local irritation, redness, or burning in the areas where the leads 
are attached. 
 
Risks and discomforts associated with Oxytocin:  
We do not expect any risks from OT injected in the skin beyond possible headache, facial flushing, and 
sensation of heart pounding. Skin injection of OT has been conducted in only one published human study. In 
this study subcutaneous injection of 4 μg/4 ml OT just prior to surgical incision resulted in more stable 
hemodynamic parameters during surgery and reduced postsurgical pain. Adverse events were not 
systematically addressed in this paper, however no gross problems were reported. 
 
Other routes of peripheral and systemic OT administration have demonstrated safety in healthy volunteers. 
Most clinical reports of intranasal oxytocin fail to mention adverse events or state that no serious or severe 
adverse events were noted. A few reports provide more detail, including a study of 49 older men (age 73 
years; range 65-78) which observed no serious adverse events and no difference between 41µg intranasal OT 
and placebo 28, and a pediatric study 29 and meta-analysis showing no safety signals with prolonged intranasal 
oxytocin administration for weeks 30. 
 
For intramuscular (IM) injection of oxytocin, only 1 study has been conducted in non-pregnant/postpartum 
persons; in these healthy participants, IM injection of 10IU (~17 μg) oxytocin (EVER Neuro Pharma GmbH, 
Unterach, Austria) in the thigh did not cause any serious adverse events or clinically significant findings for any 
safety parameters31. OT produces no tissue toxicity in these concentrations when injected intravascularly or 
into the muscle. Based on preliminary studies with intravenous and intranasal administration of oxytocin from 
the lab of James Eisenach at Wake Forest University, particularly at plasma oxytocin concentrations > 350 
pg/ml, the following adverse events may occur: headache; facial flushing; sensation of heart pounding.  
 
IV and IM OT (10IU) are frequently given for labor augmentation and postpartum hemorrhage. Based on long 
and widespread use in obstetrics, the following risks and side effects have been reported from intravenous 
and intranasal injection of oxytocin within the dosage recommendations to pregnant and immediate 
postpartum women: anaphylactic reaction; cardiac arrhythmia; fatal afibrinogenemia; nausea and vomiting; 
premature ventricular contractions; subarachnoid hemorrhage; hypertensive episodes; postpartum 
hemorrhage; pelvic hematoma; rupture of the uterus; severe water intoxication with convulsions, coma, or 
death with a slow oxytocin infusion over a 24-hr period. Because the dose of oxytocin we will be injecting is far 
lower than the 10IU dose administered to pregnant and postpartum women28 and the ~24IU dose 
administered intranasally for research purposes23, we do not expect any of the above side effects to occur. Of 
course, given the effects of OT on pregnancy, we will exclude all pregnant persons to eliminate reproductive 
risk. 
 
Risks and discomforts associated with subcutaneous injection:  
The main risks of a subcutaneous injection are pain, redness, swelling, itchiness, bruising, or irritation around 
the site of injection for 1-2 days after injection. Rare complications include infection of the puncture or 
accidental injection into a blood vessel or nerve This is not expected to increase risk given the demonstrated 
safety of larger doses of intravenous OT described above.  
 
Risks and discomforts associated with blood draw (funds permitting for baseline OT assay): 
The main risks of drawing blood from a vein include discomfort at the site of puncture, possible bruising and 
swelling around the puncture site, and (rarely) an infection or faintness from the procedure. Some subjects 


 
 
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could experience a vasovagal (fainting) response due to the discomfort of needle insertion or anxiety 
associated with the procedure. 
 
Risks and discomforts associated with heat pain stimuli: 
Reddening/darkening of the skin may occur with thermal stimulation; this is transient and disappears after 
termination of the testing. The heat stimuli, which are of moderate to strong intensity, will not damage the skin. 
Heat pain stimulation has been used extensively without any long-term adverse effects and do not cause 
permanent tissue damage [29-31]. 
 
Risks and discomforts associated with sensory stimuli: 
Mechanical and pressure pain stimuli may be slightly uncomfortable or cause brief skin irritation. Stimuli will 
not break or damage the skin. There are no known risks of the gentle brushing although some participants 
could experience it as uncomfortable. 
 
Risk of Breach of Confidentiality:  
There is a risk that information collected in our study could become known to individuals not involved in our 
study. All data are associated only with identification numbers. Breaches in confidentiality could impact future 
insurability or employability. However, in our experience, this has not occurred with this type of research. 
 
15. RISK MANAGEMENT PROCEDURES AND ADEQUACY OF RESOURCES 
 
Privacy of participants: 
Research staff will be trained by the PI to respect the privacy and confidentiality of NIH employees and staff, 
especially with regard to sensitive, private information. All data will be de-identified and personnel will not view 
data alongside identifying information, which will reduce the possibility that lab personnel would be able to 
associate sensitive information with individuals. The lab will discuss professionalism and confidentiality, and if 
lab personnel are acquainted with any potential participants, a different investigator will interact with that 
participant. 
  
Confidentiality of Data: 
We will actively protect confidentiality of the subjects and the data at each step. All medical records and 
subject data will be kept confidential and will only be reviewed by the participating investigators. Data will be 
de-identified and stored using codes that we assign. De-identified data will be kept on password-protected 
computers or in locked cabinets at UC San Diego. Only study investigators will have access to the data. 
 
Screening and questionnaires: 
Participants will be informed that they can skip any questions they do not wish to answer, and that 
participation is voluntary. If participants are triggered by items on study questionnaires, they will be offered a 
break to disengage from the task and asked whether they wish to continue or not. If participants remain upset 
referrals to psychological care at UC San Diego will be made. 
 
Heart rate recording (ECG): 
ECG leads will be removed gently and skin will be examined before and after to ensure absence of any 
irritation. 
 
Oxytocin: 
All participants will be screened to ensure they are not pregnant (including urine pregnancy test for those 
capable of pregnancy) and do not have any medical counterindications to receiving oxytocin. These 
participants will also be asked to either abstain from sexual intercourse or use a reliable, effective 
contraception during the study. The study dose is 10x smaller than doses typically administered intranasally of 
~24IU23 or 41 μg (also about 24IU) 28, and almost 5x smaller than those given intramuscularly or intravenously 


 
 
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for labor augmentation (10IU)32. In addition, blood pressure and oxygenation will be monitored regularly after 
OT injection. 
 
Subcutaneous injection: 
The injection site will be cleaned using sterile technique. If subjects are injured by study procedures they will 
be evaluated by the study physician will be treated by care providers at UC San Diego. 
 
Blood draw: 
The risks of discomfort, bruising, and swelling around the puncture site are common while the risks of infection 
and fainting are rare. The risk of fainting will be reduced by observing subjects during and following 
venipuncture to ensure that they feel comfortable rising from their seated position. Subjects with a history of 
vasovagal responses will be excluded. 
 
Heat and sensory stimuli: 
Sensory testing procedures and risks will be described carefully and participants will be encouraged to provide 
immediate feedback if a stimulus is not tolerable. If subjects want to stop pain stimulation, they may remove 
their limb for the test apparatus and ask to stop, and may be dismissed. 
 
All risks to subjects are minimal and unlikely to have significant impact. If subjects are injured by study 
procedures they will be evaluated by the study physician will be treated by care providers at UC San Diego. 
Incidental findings such as from the pregnancy tests will be shared with the subject by a medical provider 
affiliated with the study and appropriate referrals for follow-up care will be made. 
 
Monitoring: 
 
This study will follow the Data and Safety Monitoring Plan prepared for NIH: 
Data and Safety Monitoring 
The principal investigator will be responsible for the overall monitoring of the data and safety of study 
participants.  The principal investigator will be assisted by other members of the study staff. 
 
The DSMP outlined below will provide appropriate oversight and monitoring to ensure the safety of 
participants, the validity of the data, and make intermittent recommendations whether to continue, modify or 
stop the study. The DSMP will utilize an independent DSMB to ensure the effective institution of the DSMP. 
 
This DSMB will have discretion to unblind any results, or conduct any inquiry needed to ensure the safety and 
efficacy of the trial at the request of the DSMB chair. The committee will maintain a written record of its 
meetings. 
 
Scope of Data Monitoring 
The primary source of the data will be adverse event reporting. 
 
Study admission data 
Monitoring of admission data will include the number of subjects requesting participation in the study, number 
of subjects screened and number of subjects admitted to the study. The DSMB may request a report of the 
reason why subjects were disqualified from participating in the study. For subjects admitted to the study, the 
DSMB will review eligibility criteria for admitted subject, any protocol deviations and/or violations, and the 
demographic distribution of the subjects by group. 
 
Protocol Compliance 
The DSMB will monitor the data to assess compliance with the protocols including the adherence to the 
randomization schedule. The DSMB will also monitor the quality and completeness of the data being collected, 
including the frequency of missing or erroneous data, and presence and frequency of outliers. 
 


 
 
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Safety Data 
Monitoring of safety data will include review of Adverse Events (AEs) and Serious Adverse Events (SAEs), 
trial retention, and reason for drop out. Safety information will be reported to the DSMB in an unblinded 
manner. Formal statistical analyses of the safety data may be requested by the DSMB. For SAEs, data will 
include all the adverse event data meeting the FDA definition of serious adverse events. In the assessment of 
SAEs, the DSMB will review each individual case including treatment group assignment. After each meeting of 
the DSMB, the secretary will forward a summary report of all serious and unexpected adverse experiences to 
the principal investigator to summarize the DSMB's review of the serious and unexpected adverse events 
reported. Furthermore, the DSMB will make a recommendation to continue, modify or halt the study protocol. 
This report will be transmitted to the UC San Diego IRB and NIH. Safety data will be prepared for review 
following the enrollment of each 10 subjects. 
 
Establishing a DSMB Board membership 
The DSMB will be appointed by Dr. Case and Dr. Said with the purpose of reviewing, approval, and monitoring 
the implementation of the DSMP. The DSMB will have two members encompassing multidisciplinary expertise 
who are not involved in the study protocol. Board members will have no financial and/or scientific ties to the 
outcome of the clinical trials to avoid any real or perceived conflict of interest. At the start of each new 
member's term, the individual will sign a confidentiality statement promising not to disclose any proprietary and 
nonproprietary data. 
 
 
Board meeting schedule 
The board will have scheduled meetings twice a year and expedited meetings to review unexpected SAEs or 
other urgent issues that may arise during the trial. Unscheduled meetings may be initiated by the DSMB chair, 
Dr. Case, or Dr. Said. The data to be reviewed by the DSMB will be available to the Board members. 
 
DSMB Recommendations: 
DSMB recommendations will be made in writing by The DSMB chair to Dr. Case. DSMB recommendations will 
then be forwarded to the NIH program officer and UC San Diego IRB. 
 
 
Adverse Event (AE):  
An adverse event (AE) is any untoward medical occurrence in a subject during participation in the clinical 
study or with use of the experimental agent being studied. An adverse finding can include a sign, symptom, 
abnormal assessment (laboratory test value, vital signs, electrocardiogram finding, etc.), or any combination of 
these regardless of relationship to participation in the study.  
 
Unanticipated Problems (UP):  
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
subjects or others to include, in general, any incident, experience, or outcome that meets all of the following 
criteria:  
● Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the subject population being studied; 
● Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and  
● Suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  
 
Serious Adverse Event (SAE): 
A serious adverse event (SAE) is one that meets one or more of the following criteria:  
● Results in death 


 
 
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● Is life-threatening (places the subject at immediate risk of death from the event as it occurred)  
● Results in inpatient hospitalization or prolongation of existing hospitalization 
● Results in a persistent or significant disability or incapacity  
● Results in a congenital anomaly or birth defect 
 
An important medical event that may not result in death, be life threatening, or require hospitalization may be 
considered an SAE when, based upon appropriate medical judgment, the event may jeopardize the subject 
and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. 
 
Time Period and Frequency for Event Assessment and Follow-Up:  
Unanticipated problems will be recorded in the data collection system throughout the study.  
 
The PI will record all reportable events occurring during the testing session or reported by the participant to the 
PI within 30 days of the testing session. If participating in multiple study session, at each study visit, the 
investigator will inquire about the occurrence of AE/SAEs since the last visit. Events will be followed for 
outcome information until resolution or stabilization. 
 
Characteristics of an Adverse Event Relationship to Study Intervention:  
To assess relationship of an event to study intervention, the following guidelines are used:  
● Related (Possible, Probable, Definite) 
o The event is known to occur with the study intervention.  
o There is a temporal relationship between the intervention and event onset.  
o The event abates when the intervention is discontinued.  
o The event reappears upon a re-challenge with the intervention.  
● Not Related (Unlikely, Not Related)  
o There is no temporal relationship between the intervention and event onset.  
o An alternate etiology has been established.  
 
Expectedness of SAEs:  
The Study PI and Independent Monitoring Committee will be responsible for determining whether an SAE is 
expected or unexpected. An adverse event will be considered unexpected if the nature, severity, or frequency 
of the event is not consistent with the risk information previously described for the intervention.  
 
Severity of Event: 
The following scale will be used to grade adverse events:  
● Mild: no intervention required; no impact on activities of daily living (ADL)  
● Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on ADL  
● Severe: significant symptoms requiring invasive intervention; subject seeks medical attention, needs 
major assistance with ADL  
 
Unanticipated Problem Reporting: 
Incidents or events that meet the OHRP criteria for unanticipated problems require the creation and 
completion of an unanticipated problem report form. OHRP recommends that investigators include the 
following information when reporting an adverse event, or any other incident, experience, or outcome as an 
unanticipated problem to the IRB: 
● Appropriate identifying information for the research protocol, such as the title, investigator’s name, and 
the IRB project number;  
● A detailed description of the adverse event, incident, experience, or outcome; 
● An explanation of the basis for determining that the adverse event, incident, experience, or outcome 
represents an unanticipated problem;  
● A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the unanticipated problem.  
 


 
 
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To satisfy the requirement for prompt reporting, unanticipated problems will be reported using the following 
timeline:  
● Unanticipated problems that are serious adverse events will be reported to the IRB, Independent 
Safety Monitor(s), and NIH within 7 days of the investigator becoming aware of the event.  
● Any other unanticipated problem will be reported to the IRB, Independent Safety Monitor(s), and NIH 
within 14 days of the investigator becoming aware of the problem.  
 
Adverse Event Reporting for IND Studies:  
SAEs that are unanticipated, serious, and possibly related to the study intervention will be reported to the 
Independent Monitors(s), IRB, FDA, and NIH in accordance with requirements.  For the IND:  
● 7-day IND Safety Report (unexpected fatal or life-threatening AEs related to the intervention); a copy of 
the report sent to the FDA will be submitted to the NIH Program Officer and Independent Safety 
Monitor(s) within 24 hours of FDA notification.  
● 15-day IND Safety Report (any other serious and unexpected AE related to the intervention); a copy of 
the report submitted to the FDA will be submitted to the NIH Program Officer and Independent Safety 
Monitor(s) within 24 hours of FDA notification.  
● All other AEs documented during the course of the trial will be reported to NIH on an annual basis by 
way of inclusion in the annual report and in the annual AE summary which will be provided to NIH and 
to the Independent Monitors.  The Independent Safety Monitor(s) Report will state that all AEs have 
been reviewed. 
 
Halting Rules: 
The study will be halted Halt if any SAE related to study participation or two severe AEs/reactions occur, until 
a complete safety review is convened.  
 
Measurement and Reporting of Subject Accrual:  
Review of the rate of subject accrual will occur monthly during the recruitment phase to ensure that a sufficient 
number of participants are being enrolled, in keeping with proposed recruitment projections, and that they 
meet eligibility criteria and fulfill the targeted ethnic diversity goals outlined in the grant proposal. 
 
16. PRIVACY AND CONFIDENTIALITY CONSIDERATIONS INCLUDING DATA ACCESS AND 
MANAGEMENT 
 
Study recruitment and enrollment will be monitored through a Screening/Enrollment Log, both created as 
password protected Microsoft Excel spreadsheets. No identifying information will be used on any study 
documents after enrollment. Enrolled subjects will be assigned a unique subject identification number (SID) 
that will be used on all Case Report Forms (CRFs) and study related documents after enrollment. The SID will 
be linked to subject identifiable information only in the Screening/Enrollment Log, created and password 
protected in a Microsoft excel spreadsheet. This will be stored on a coordinator’s password protected and 
encrypted computer in the ACTRI.  
 
To minimize possible risk of breach of confidentiality, the SID will be used for each subject as the unique 
identifier for all research related activities. All information collected, including self-report questionnaires, 
psychological assessments, and sensory data will be identified solely by the SID and without any personal 
identifiers. Electronic data will be stored on password protected computers on servers in the ACTRI. Only 
strictly anonymous data will be entered into electronic databases and used for statistical analysis. Access to 
the participant numbering system will be limited to the Principal Investigator and the research staff involved in 
the study. Research files will be kept in locked cabinets or drawers in a locked office or clinic or storage room, 
in the ACTRI, and made available only to qualified personnel for research purposes. No verbal or written 
information concerning a subject will be released to anyone without expressed written consent by the subject.  
Any data shared with the sponsor will be transferred electronically with no identifiers whatsoever.  


 
 
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As part of consent procedures, participants will be advised of precautions taken to preserve confidentiality. 
Further, all individuals involved in data collection procedures will be instructed to not divulge any information 
concerning participants to any person or agency without the written and explicit consent of the patients.  These 
procedures have been effective in completely protecting patient information in past studies. All study staff 
receive Good Clinic Practice and Human Subjects Protection training as well as HIPAA privacy training before 
working with any participants. No published or presented materials will identify patients by names, initials, or 
any other means that could be used to identify the participant. 
 
Recruitment will take place from private office and clinic areas. Recruitment will not take place in an open 
public area, hallways, a crowded waiting room, or other venue that would jeopardize participant privacy.  The 
informed consent process will take place in a private room at the ACTRI where the participant can ask 
questions without feelings of embarrassment or discomfort. 
 
 
17. POTENTIAL BENEFITS 
There are no direct benefits from participating in this study. Each participant will receive financial 
compensation for participating in the study, but all participants will be informed that there are no direct benefits 
to them for participating in the research study.  
 
Study participants may gain satisfaction from the knowledge that they are contributing to a better 
understanding the neurobehavioral underpinnings of affective touch and pain perception, with potential 
applications for chronic pain. 
 
18. RISK/BENEFIT RATIO 
There are no alternative procedures that will provide comparable information to that obtained by the methods 
described in this study. The risks for this study are small in comparison to the substantial anticipated benefits 
regarding better understanding of mechanisms of pain and touch perception.  
 
19. EXPENSE TO PARTICIPANT 
 
There will be no expense to the participant except for their transportation. 
 
20. COMPENSATION FOR PARTICIPATION 
 
Participants will receive $80 for the Baseline session, $60 for Session 2, for a total of $140.  A free parking 
voucher code will be made available for each study session. 
 
21. PRIVILEGES/CERTIFICATIONS/LICENSES AND RESEARCH TEAM RESPONSIBILITIES 
All personnel will be trained by Dr. Case or Dr. Said and/or Dr. Schuster (when needed) to perform their 
respective study procedures before any participants are screened or enrolled. 
 
Dr. Laura Case, PhD— Principal Investigator 
• 
Role/Responsibilities:  
o Oversees all study members, procedures, information, and research activities. She can and 
may review medical record history to confirm diagnosis. 
• 
Qualifications/Certifications/Licenses:  
o CITI Training in Biomedical Research and Good Clinical Practice 
o PhD in Experimental Psychology 
o Postdoctoral training in pain research and brain imaging 
 


 
 
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Dr. Engy T. Said, MD— Co-Investigator 
• 
Role/ Responsibilities:  
• 
Oversees all study members, procedures, information, and research activities. 
• 
Consulting study physician 
• 
Qualifications/Certifications/Licenses:  
• 
CITI Training in Biomedical Research and Good Clinical Practice 
• 
Board-certified anesthesiologist with fellowship training in regional anesthesia and acute pain. Dr. Said 
holds a license to practice medicine in California, has medical privileges at the UC Medical Centers, 
and will be responsible for the overall management of this study. 
 
Dr. Nathaniel M. Schuster, MD – Co-Investigator 
• 
Role/Responsibilities:  
o Consulting study physician 
• 
Qualifications/Certifications/Licenses:  
o CITI Training in Biomedical Research and Good Clinical Practice 
o California Medical License to practice as a Physician and Surgeon by the Medical Board of 
California 
 
Dr. Hemal Patel, PhD – Co-Investigator 
• 
Role/Responsibilities:  
o Conduct ELISA assays for oxytocin 
• 
Qualifications/Certifications/Licenses:  
o Professor, Dept of Anesthesiology 
o Will not interact with human subjects 
 
Dr. Benedetta Albinni, PhD – Post-Doctoral Researcher 
• 
Role/Responsibilities:  
o Assists to oversee all study members, procedures, information, and research activities. She can 
and may review medical record history to confirm diagnosis. She will assist with all aspects of 
the study, including coordinating, collecting data, and conducting sensory testing across all 
study sessions. She may also assist with recruitment methods, including in-person recruitment 
at the UCSD pain clinic, conducting phone screenings, consent procedures, randomization, 
scheduling, and acting as a communication point for the study. She will help maintain IRB 
binders and corresponding duties and can and may review medical records to confirm 
diagnosis and collect self-report information (including PHI). 
• 
Qualifications/Certifications/Licenses:                     
o CITI Training in Biomedical Research and Good Clinical Practice 
o PhD in Cognitive Neuroscience 
 
Vincent Alasha, BA in Psychology – Research Assistant 
• 
Roles/Responsibilities: Mr. Alasha will assist with all aspects of the study, including coordinating, 
collecting data, and conducting sensory testing across all study sessions. He may also assist with 
recruitment methods, including in-person recruitment at the UCSD pain clinic, conducting phone 
screenings, consent procedures, randomization, scheduling, and acting as a communication point for 
the study. He will help maintain IRB binders and corresponding duties and can and may review 
medical records to confirm diagnosis and collect self-report information (including PHI). 
• 
Qualifications/Certifications/Licenses 
o CITI Training in Biomedical Research and Good Clinical Practice 
o BA in Psychology 
 
Michael Haupt, UCSD Graduate Student in Cognitive Science – Research Assistant 


 
 
Biomedical IRB Application Instructions 
Page 18 
• 
Roles/Responsibilities: Mr. Haupt will assist with data collection and conducting sensory testing across 
all study sessions. He will also assist with data analysis. 
• 
Qualifications/Certifications/Licenses: 
o CITI Training in Biomedical Research and Good Clinical Practice  
o MA in Quantitative Methods in the Social Sciences 
 
Marisa Zimmerman, BS in Cognitive and Behavioral Neuroscience – Research Assistant 
• 
Roles/Responsibilities: Ms. Zimmerman will assist with all aspects of the study, including coordinating, 
collecting data, and conducting sensory testing across all study sessions. She may also assist with 
recruitment methods, including in-person recruitment at the UCSD pain clinic, conducting phone 
screenings, consent procedures, randomization, scheduling, and acting as a communication point for 
the study. She will help maintain IRB binders and corresponding duties and can and may review 
medical records to confirm diagnosis and collect self-report information (including PHI). 
• 
Qualifications/Certifications/Licenses 
o CITI Training in Biomedical Research and Good Clinical Practice 
o  BS in Cognitive and Behavioral Neuroscience 
 
Benjamin Goldstein, UCSD Medical Student  
• 
Roles/Responsibilities: Mr. Goldstein will assist with all aspects of the study, including coordinating, 
collecting data, and conducting sensory testing across all study sessions. He may also assist with 
recruitment methods, including in-person recruitment at the UCSD pain clinic, conducting phone 
screenings, consent procedures, randomization, scheduling, and acting as a communication point for 
the study. He will help maintain site regulatory binders and corresponding duties and can and may 
review medical records to confirm diagnosis and collect self-report information (including PHI). 
• 
Qualifications/Certifications/Licenses   
o CITI Training in Biomedical Research and Good Clinical Practice 
o Current Medical student 
 
Jacob Ross, UCSD student in Neurobiology – Research Volunteer 
• 
Roles/Responsibilities: Mr. Ross will assist with all aspects of the study, including coordinating, 
collecting data, and conducting sensory testing across all study sessions. He may also assist with 
recruitment methods, including in-person recruitment at the UCSD pain clinic, conducting phone 
screenings, consent procedures, randomization, scheduling, and acting as a communication point for 
the study. He will help maintain IRB binders and corresponding duties and can and may review 
medical records to confirm diagnosis and collect self-report information (including PHI). 
• 
Qualifications/Certifications/Licenses 
o CITI Training in Biomedical Research and Good Clinical Practice 
o  BS in Neurobiology 
 
Leyla Ozdoyuran, UCSD student in Clinical Psychology – Research Volunteer 
• 
Roles/Responsibilities: Ms. Ozdoyuran will assist with all aspects of the study, including coordinating, 
collecting data, and conducting sensory testing across all study sessions. She may also assist with 
recruitment methods, including in-person recruitment at the UCSD pain clinic, conducting phone 
screenings, consent procedures, randomization, scheduling, and acting as a communication point for 
the study. She will help maintain IRB binders and corresponding duties and can and may review 
medical records to confirm diagnosis and collect self-report information (including PHI). 
• 
Qualifications/Certifications/Licenses 
o CITI Training in Biomedical Research and Good Clinical Practice 
o  BS in Clinical Psychology in progress 
 
We will likely hire another (TBD) post-doctoral fellow or research assistant to help with the data collection. 
 


 
 
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Registered Nurses in the ACTRI may administer subcutaneous injections. 
  
22. BIBLIOGRAPHY 
 
 
 
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Johannes, C. B., Le, T. K., Zhou, X., Johnston, J. A. & Dworkin, R. H. The prevalence of chronic pain in United States 
adults: results of an Internet-based survey. The Journal of Pain 11, 1230-1239 (2010). 
2 
Dahlhamer, J. et al. Prevalence of chronic pain and high-impact chronic pain among adults—United States, 2016. Morbidity 
and Mortality Weekly Report 67, 1001 (2018). 
3 
Sundberg, T., Cramer, H., Sibbritt, D., Adams, J. & Lauche, R. Prevalence, patterns, and predictors of massage practitioner 
utilization: Results of a US nationally representative survey. Musculoskeletal Science and Practice 32, 31-37 (2017). 
4 
Case, L. K. et al. Pleasant Deep Pressure: Expanding the Social Touch Hypothesis. Neuroscience (2020). 
5 
Pawling, R., Trotter, P. D., McGlone, F. P. & Walker, S. C. A positive touch: C-tactile afferent targeted skin stimulation 
carries an appetitive motivational value. Biological Psychology 129, 186-194 (2017). 
6 
Triscoli, C., Croy, I., Steudte-Schmiedgen, S., Olausson, H. & Sailer, U. Heart rate variability is enhanced by long-lasting 
pleasant touch at CT-optimized velocity. Biological psychology 128, 71-81 (2017). 
7 
Froemke, R. C. & Young, L. J. Oxytocin, neural plasticity, and social behavior. Annual Review of Neuroscience 44 (2021). 
8 
Uvnäs-Moberg, K., Handlin, L. & Petersson, M. Self-soothing behaviors with particular reference to oxytocin release 
induced by non-noxious sensory stimulation. Frontiers in psychology 5, 1529 (2015). 
9 
Gonzalez-Hernandez, A. & Charlet, A. Oxytocin, GABA, and TRPV1, the analgesic triad? Frontiers in molecular 
neuroscience 11, 398 (2018). 
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Poisbeau, P., Grinevich, V. & Charlet, A. Oxytocin signaling in pain: cellular, circuit, system, and behavioral levels. 
Behavioral pharmacology of neuropeptides: oxytocin, 193-211 (2017). 
11 
Walker, S. C., Trotter, P. D., Swaney, W. T., Marshall, A. & Mcglone, F. P. C-tactile afferents: Cutaneous mediators of 
oxytocin release during affiliative tactile interactions? Neuropeptides 64, 27-38 (2017). 
12 
Stock, S. & Uvnäs‐Moberg, K. Increased plasma levels of oxytocin in response to afferent electrical stimulation of the 
sciatic and vagal nerves and in response to touch and pinch in anaesthetized rats. Acta physiologica scandinavica 132, 29-34 
(1988). 
13 
Tang, Y. et al. Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons. Nature 
Neuroscience 23, 1125-1137 (2020). 
14 
Chen, Y. et al. The effects of intranasal oxytocin on neural and behavioral responses to social touch in the form of massage. 
Frontiers in neuroscience 14, 1286 (2020). 
15 
Juif, P.-E. & Poisbeau, P. Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in 
male rats. PAIN® 154, 1449-1456 (2013). 
16 
Eliava, M. et al. A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and 
inflammatory pain processing. Neuron 89, 1291-1304 (2016). 
17 
Grinevich, V. & Charlet, A. Oxytocin: pain relief in skin. Pain 158, 2061-2063 (2017). 
18 
González-Hernández, A. et al. Peripheral oxytocin receptors inhibit the nociceptive input signal to spinal dorsal horn wide-
dynamic-range neurons. Pain 158, 2117-2128 (2017). 
19 
González-Hernández, A., De Los Monteros-Zuñiga, A. E., Martínez-Lorenzana, G. & Condés-Lara, M. Recurrent 
antinociception induced by intrathecal or peripheral oxytocin in a neuropathic pain rat model. Experimental brain research 
237, 2995-3010 (2019). 
20 
Boada, M. D., Gutierrez, S. & Eisenach, J. C. Peripheral oxytocin restores light touch and nociceptor sensory afferents 
towards normal after nerve injury. Pain 160, 1146-1155 (2019). 
21 
Hilfiger, L. et al. A nonpeptide oxytocin receptor agonist for a durable relief of inflammatory pain. Scientific reports 10, 1-
10 (2020). 
22 
Zayas‐González, H. et al. Effect of local infiltration with oxytocin on hemodynamic response to surgical incision and 
postoperative pain in patients having open laparoscopic surgery under general anesthesia. European Journal of Pain 23, 
1519-1526 (2019). 
23 
Chen, Y. et al. Oxytocin increases the pleasantness of affective touch and orbitofrontal cortex activity independent of 
valence. European Neuropsychopharmacology 39, 99-110 (2020). 
24 
Rolke, R. et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized 
protocol and reference values. Pain 123, 231-243 (2006). 
25 
Rolke, R. et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. European journal of pain 10, 77-88 
(2006). 


 
 
Biomedical IRB Application Instructions 
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Hicks, C. et al. Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the 
non‐peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats. British journal of pharmacology 171, 
2868-2887 (2014). 
27 
Baron-Cohen, S., Wheelwright, S., Skinner, R., Martin, J. & Clubley, E. The autism-spectrum quotient (AQ): evidence from 
Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord 31, 5-
17 (2001). 
28 
Rung, J. M. et al. Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled 
trial. Psychopharmacology (Berl) 238, 2405-2418, doi:10.1007/s00213-021-05862-3 (2021). 
29 
DeMayo, M. M., Song, Y. J. C., Hickie, I. B. & Guastella, A. J. A Review of the Safety, Efficacy and Mechanisms of 
Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and 
Recommendations for Future Research. Paediatr Drugs 19, 391-410, doi:10.1007/s40272-017-0248-y (2017). 
30 
Cai, Q., Feng, L. & Yap, K. Z. Systematic review and meta-analysis of reported adverse events of long-term intranasal 
oxytocin treatment for autism spectrum disorder. Psychiatry Clin Neurosci 72, 140-151, doi:10.1111/pcn.12627 (2018). 
31 
Fernando, D. et al. Safety, tolerability and pharmacokinetics of single doses of oxytocin administered via an inhaled route in 
healthy females: randomized, single-blind, phase 1 study. EBioMedicine 22, 249-255 (2017). 
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Adnan, N., Boland, F. & Murphy, D. J. Intramuscular oxytocin versus intravenous oxytocin to prevent postpartum 
haemorrhage at vaginal delivery (LabOR trial): study protocol for a randomised controlled trial. Trials 18, 1-10 (2017). 
 
  
23. FUNDING SUPPORT FOR THIS STUDY 
An ACTRI Pilot Award application has been submitted for funding consideration. 
 
24. BIOLOGICAL MATERIALS TRANSFER AGREEMENT 
Not applicable. 
 
25. INVESTIGATIONAL DRUG FACT SHEET AND IND/IDE HOLDER 
An IND application (sponsor Laura Case PhD) has been submitted to the FDA for subcutaneous injection of 
oxytocin for research purposes. An investigational drug fact sheet is appended. 
 
26. IMPACT ON STAFF 
Not applicable. 
 
27. CONFLICT OF INTEREST 
The PI and all key personnel report no conflicts of interest.  
 
28. SUPPLEMENTAL INSTRUCTIONS FOR CANCER-RELATED STUDIES 
Not applicable. 
 
29. OTHER APPROVALS/REGULATED MATERIALS 
Not applicable. 
 
30. PROCEDURES FOR SURROGATE CONSENT AND/OR DECISIONAL CAPACITY ASSESSMENT 
Those trained to screen subjects will be responsible for determining the decisional capacity of the subjects 
being considered for inclusion in the protocol. During the consent process, those screening subjects will 
reiterate study details and will assess for an understanding of the required study involvement. These details 
include the nature of pain tasks, the duration of study, and maximum and partial compensation. If the 
decisional capacity is questionable, further evaluation will be performed and documented in regard to this 
matter. If the investigator determines that the subject lacks decision-making capacity, they will not enroll the 
subject into the study. 
 
 

ICF_001.pdf: 
Peripheral Oxytocin and Touch (POPP) 
 
NCT05326776 
 
Study Consent 
 
Version date: 3/16/2023 


 
 
 
 
University of California, San Diego 
Consent to Act as a Research Subject 
 
Effect of Peripheral Oxytocin on Touch Pleasantness and Pain 
 
Introduction 
 
Dr. Laura Case and associates are conducting this research and asking for your consent to 
participate. This section provides a summary of important information. The rest of the form 
provides additional details. 
 
• Research is voluntary - whether or not you join is your decision. You can discuss your 
decision with others (such as family, friends or another physician). 
• You can say yes but change your mind later. 
• If you say no, we will not hold your decision against you. 
• Your decision will not affect any other benefits you may be entitled to. 
• You can say no even if the person inviting you is part of your healthcare team. 
• Please ask questions or mention concerns before, during or after the research. 
 
The purpose of this study is to learn more about oxytocin in the skin and how it affects nerves 
that send pleasant touch or pain signals to the brain. The study will examine how individuals 
perceive gentle brushing and pain stimuli before and after a skin injection of oxytocin, compared 
to a placebo saline injection. This will help us understand the role of oxytocin in the skin, and 
whether it could be used to relieve pain. Participation in the study will not benefit you directly 
but may result in new knowledge that helps others. 
 
This study has a total of two sessions, both at the Altman Clinical Research Institute (ACTRI) at 
UC San Diego. Participants who can become pregnant will undergo a urine pregnancy test at the 
start of each session. If the test is positive, you will be dismissed from the study. If you agree to 
participate in this study, you will be asked to complete questionnaires and make ratings of gentle 
brushing and a variety of pain stimuli. Photographs of your arm will be taken before and after the 
injection to document any reactions. Participation also involves receiving an injection of 
oxytocin or saline in the skin of your arm. In addition, you may receive a blood draw to measure 
levels of oxytocin, inflammation, and features of metabolism in your blood.   
 
The most commonly expected risks of the study are discomfort from the pain stimuli that are 
administered and becoming bored with the questionnaires.  
 
The most serious risks of the study include harm to a pregnant person or fetus from the oxytocin 
injection. These risks are extremely unlikely since we conduct careful screening for pregnancy 
and you may stop study procedures at any time.  
 
Additional, detailed information about this research is provided below. Please feel free to ask 
questions before signing this consent. 
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Why have you been asked to participate, how you were selected, and what is the approximate 
number of participants in the study? 
You have been asked to participate in this study because you are a healthy adult. There will be 
approximately 20 participants at this site. 
 
What will happen to you in this study and which procedures are standard of care and which 
are experimental? 
In addition to the information at the beginning of this form, here are some additional details 
about will happen to you if you agree to be in this study,  
 
Session 1: Session 1 will be split into two procedures.  
 
1) After (only if) you have signed consent, we will retain your study screening information 
as study data. You will complete the series of study questionnaires via REDCap (online 
survey software). You will then be asked about your recent behaviors regarding caffeine, 
alcohol, food, smoking, exercise, and sleep. We will then introduce you to our thermode, 
the device we use to administer the heat stimulus. The thermode will be placed against 
your forearm with temperatures ranging from mild to painful, and you will be asked to 
rate the intensity of the temperatures. There will be a short break before starting the 
second procedure.  
 
2) We will start by performing a blood draw (~10mL) to measure levels of oxytocin, 
inflammation and features of metabolism in the blood. Next, we will monitor your heart 
rate for 5 minutes. You will then be asked to make ratings of gentle brushing and a 
variety of pain stimuli, including mechanical, pressure, and heat. After the first series of 
ratings, you will receive an injection of oxytocin or saline into the skin of your forearm. 
Neither you nor the research technician will know which injection you are receiving. 
About 10 minutes after the injection, the series of gentle brushing and pain stimuli will be 
repeated. 
 
Session 1 will take approximately 1 hour and 30 minutes to complete. 
 
To ensure drug clearance, the sessions will be separated by more than two days according to the 
participant and experimenters’ availability.  
 
Session 2 will be a repeat of the second procedure in Session 1: 
 
Prior to Session 2, you will be asked about your recent behaviors regarding caffeine, alcohol, 
food, smoking, exercise, and sleep We will start by performing a blood draw (~10mL) to 
measure levels of oxytocin, inflammation, and features of metabolism in the blood. Next, we will 
monitor your heart rate for 5 minutes. You will then be asked to make ratings of gentle brushing 
and a variety of pain stimuli, including mechanical, pressure, and heat. After the first series of 
ratings, you will receive an injection of oxytocin or saline into the skin of your forearm. Neither 
you nor the research technician will know which injection you are receiving. If you received 
oxytocin in Session 1 you will receive saline in Session 2, and vice versa. About 10 minutes after 
the injection, the series of gentle brushing and pain stimuli will be repeated. 
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Session 2 will take approximately 1 hour to complete. 
 
All of these procedures are experimental and not for treatment purposes. 
 
What risks are associated with this study? 
Participation in this study may involve some added risks or discomforts. In addition to the risks 
described at the beginning of this form, 
 
1) Heart Rate Recording: Placement and removal of the leads for heart rate recording may 
cause some mild discomfort, local irritation, redness, or burning. 
 
2) Skin Injection of Oxytocin and Saline: You may experience headache, facial flushing, 
and sensation of heart pounding. There may also be pain, redness, swelling, itchiness, 
bruising, or irritation near the injection site for 1-2 days. Rare complications include 
infection or accidental injection into a blood vessel or nerve. Injections will be performed 
by a licensed healthcare professional, and we will monitor blood pressure and 
oxygenation before and after the injection. 
 
3) Blood draw: Approximately 20mL of blood will be drawn in total for this study. The 
main risks of drawing blood from a vein include discomfort, possible bruising and 
swelling around the puncture site, and (rarely) an infection or fainting from the 
procedure. 
 
4) Heat Pain Stimuli: Reddening/darkening of the skin may occur with thermal stimulation. 
This is temporary and will not damage the skin. 
 
5) Sensory Stimuli: The sensory stimuli may be slightly uncomfortable or cause brief skin 
irritation, but they will not break or damage the skin. 
 
6) Confidentiality: There is a risk that information collected in our study could become 
known to individuals not involved in our study.  Breaches in confidentiality could impact 
future insurability or employability.  However, in our experience, this has not occurred 
with this type of research. 
 
Because this is a research study, there may be some unknown risks that are currently 
unforeseeable. You will be informed of any significant new findings. 
 
Are there risks to the reproductive system or a developing fetus? 
The effects of oxytocin injection may pose some unforeseeable risks to a developing fetus. For 
this reason, you cannot participate in this study if you are pregnant. We ask that if you could 
become pregnant that you either abstain from sexual intercourse or use a reliable, effective 
contraception for this period, such as hormonal contraceptive, intrauterine device (IUD), 
diaphragm with spermicide, contraceptive sponge or use of condom by the partner. Because 
some methods of birth control are not 100% reliable, a urine pregnancy test will be required at 
the start of each session. If you have a positive pregnancy test, we will withdraw you from the 
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study. If you become pregnant or if there is any chance of pregnancy (e.g., late menstrual 
period), please contact the study personnel immediately so that we may provide medical 
assistance and counseling. 
 
What are the alternatives to participating in this study? 
You do not have to participate in this study. This is not a treatment study. The alternative to 
participating in this study is to not participate. 
 
What benefits can be reasonably expected? 
There may or may not be any direct benefit to you from these procedures. The investigator(s), 
however, may learn more about how oxytocin impacts affective touch and pain perception, with 
potential applications for treating pain.  
 
What happens if you change your mind about participating? 
Participation in research is entirely voluntary. You may refuse to participate or withdraw at any 
time without penalty or loss of benefits to which you are entitled. If you decide that you no 
longer wish to continue in this study, you will be requested to inform the investigators and tell us 
why you are leaving the study. You will be told if any important new information is found during 
the course of this study that may affect your wanting to continue. 
 
Can you be withdrawn from the study without your consent? 
You may be withdrawn from the study for the following reasons your eligibility information 
changes, or the study physicians Dr. Engy Said or Dr. Nathaniel Schuster believes that it is in 
your best medical interest to leave the study. You may also be withdrawn from the study if you 
do not follow the instructions given you by the study personnel. 
 
Will you be compensated for participating in this study? 
In compensation for your time and travel, you will receive $80 for Session 1 and $60 for Session 
2 for a total of $140. In addition, a free parking voucher will be made available for each study 
session.  
 
Are there any costs associated with participating in this study? 
There will be no cost to you for participating in this study.  
 
What if you are injured as a direct result of being in this study? 
If you are injured as a direct result of participation in this research, the University of California 
will provide any medical care you need to treat those injuries. The University will not provide 
any other form of compensation to you if you are injured. You may call the Human Research 
Protections Program Office at 858-246-HRPP (858-246-4777) for more information about this, 
to inquire about your rights as a research subject or to report research-related problems. 
 
What about your confidentiality? 
Research records will be kept confidential to the extent allowed by law. All data will be 
processed in a HIPAA-compliant fashion to ensure confidentiality. Data are assigned a unique 
identification number and stored separately from your name and other identifying information. 
Digital data will be stored on both physically and software protected computers and will only be 
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accessed by study personnel from within the medical center. Any reference to individual 
participants in reports of this work will be encoded to preserve confidentiality. 
 
Research records may be reviewed by the UCSD Institutional Review Board, The Food and 
Drug Administration (FDA) and The National Institute of Health (NIH), for example, may 
inspect research records and learn your identity if this study falls within its jurisdiction. 
 
This research is covered by a Certificate of Confidentiality from NIH. Researchers with this 
Certificate may not disclose or use information, documents, or biospecimens that may identify 
you in any federal, state, or local civil, criminal, administrative, legislative, or other action, suit, 
or proceeding, or be used as evidence unless you have consented for this use. Information, 
documents, or biospecimens protected by this Certificate cannot be disclosed to anyone else who 
is not connected with the research unless there is a federal, state, or local law that requires 
disclosure (such as to report child abuse, elder abuse, intent to hurt self or others, or 
communicable diseases), you have consented to the disclosure, including for your medical 
treatment; or it is used for other scientific research, as allowed by federal regulations protecting 
research subjects. 
 
The Certificate cannot be used to refuse a request for information from personnel of federal or 
state government agency sponsoring the project that is needed for auditing or program evaluation 
by NIH which is funding the project or for information that must be disclosed in order to meet 
the requirements of the Food and Drug Administration (FDA). You should also understand that a 
Certificate of Confidentiality does not prevent you from voluntarily releasing information about 
yourself or your involvement in this research. If you want your research information released to 
an insurer, medical care provider, or any other person not connected with the research, you must 
provide consent to allow the research to release it. 
 
Personal identifiers might be removed from the information or biospecimens collected as part of 
the research. After such removal, the information or biospecimens could be used for future 
research studies or distributed to another investigator for future research studies without your 
additional informed consent. 
 
Biospecimens (such as blood, tissue, or saliva) collected from you for this study and/or 
information obtained from your biospecimens may be used in this research or other research, and 
shared with other organizations. You will not share in any commercial value or profit derived 
from the use of your biospecimens and/or information obtained from them. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
Will you receive any results from participating in this study? 
You will not receive any results from participating in this study. 
 
Who can you call if you have questions? 
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This study has been explained to you and your questions have been answered. If you have other 
questions or research-related problems, you may reach Dr. Laura Case at 858-246-4968. 
 
You may call the Human Research Protections Program Office at 858-246-HRPP (858-246-
4777) to inquire about your rights as a research subject or to report research-related problems. 
 
Your Signature and Consent 
You have received a copy of this consent document and a copy of the “Experimental Subject's 
Bill of Rights” to keep. 
 
You agree to participate. 
 
 
_____________________________________________________  
_______________ 
Subject's signature 
 
 
 
 
 
 
 
Date 
 
 
_________________________________________________ 
_______________ 
Signature of the person conducting  
 
 
 
 
Date 
the informed consent discussion 
 
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