Clinical trial NCT04105998
Conditions: Chronic Pain Due to Injury
Keywords: Healthy Volunteer Oxytocin Pupillometry
Sponsor: Wake Forest University Health Sciences
Start date: 2019-10-24; Completion date: 2021-11-01
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The goal of this study is to test the effects of oxytocin on heart rate variability and pupil diameter, both of which have subtle effects on the activity rate of the autonomic nervous system.

Detailed description:
This protocol focuses on two measures of autonomic control to quantify central actions of oxytocin. First, the study team proposes to examine the influence of oxytocin on heart rate variability with focus on its effect on high frequency variability, most commonly ascribed to parasympathetic nervous system activity acting to brake sympathetic tone. Intranasal oxytocin has been demonstrated to have a large effect size on this measure which can be repeated at frequent intervals. As a secondary assessment of parasympathetic activity, the study team will measure low frequency fluctuation in pupil diameter, termed hippus, which also reflects parasympathetic nervous system activity. This outcome measure can be assessed in 3 seconds using equipment currently being used under Institutional Review Board (IRB) approved protocols.

Arms: arm 1: Subjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®), 10 International Units (IU) at the first visit. Then at the next visit, they will receive Intramuscular injection of (1 milliliter) saline. arm 2: Subjects in this arm will receive intramuscular injection of (1 milliliter) saline at the first visit. Then at the next visit, they will receive Intramuscular injection of Oxytocin (Pitocin®), 10 International Units (IU).
Interventions: intervention 1: Oxytocin intervention 2: Placebo
Intervention descriptions: intervention 1: Oxytocin 10 IU intervention 2: Placebo

Protocol documents:
Prot_SAP_001.pdf: 
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Version 10/18/2021 
NCT04105998 
Title: Effects of Intramuscular Oxytocin on Pupil Diameter and Heart Rate 
Variability 
Date: 10/18/2021 
 


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BACKGROUND 
 
A large body of evidence in animals and in humans suggest that oxytocin can 
produce analgesia to experimental pain stimuli and relieve pain in acute and chronic 
clinical pain states.  For the past 8 years we have, under an NIH MERIT award, tested 
the role of the spinal cord in oxytocin’s actions by studies in rodents and clinical trials, 3 
of which are ongoing, of spinally injected oxytocin. 
 
The Pain Mechanisms Laboratory at Wake Forest is now in the process of 
assembling an NIH program project grant (P01) on the topic of oxytocin sites, 
mechanisms, and clinical applications for analgesia, and Dr. Eisenach will lead the 
clinical project in that proposal.  In order to acquire adequate preliminary data to support 
this application, we are examining the effects of oxytocin in several small clinical 
studies. The first one of these (IRB 00056413) has been completed, and described the 
pharmacokinetics of oxytocin, 10 IU, after intravenous administration in men and 
women.  The second one (IRB00056660) is ongoing and examines intramuscular 
oxytocin, 10 IU, compared to placebo in a double blinded study on sensory changes 
after controlled UV-B sunburn.  We have obtained a waiver of IND from the FDA for 
oxytocin at these doses by these routes of administration in men and women. 
 
The goal of this third protocol is to test central effects of Intramuscular oxytocin 
on noninvasive measures which can be easily and repeatedly assessed.  The first two 
studies are providing information related to dosing of oxytocin and measurement of its 
effects on sensory nerves in the periphery.  Oxytocin also enters the central nervous 
system after systemic administration, and the goal of the current study is to test the 
effects of oxytocin on heart rate variability and pupil diameter, both of which affect 
subtle effects on autonomic tone and which have been proposed in earlier studies by 
others to be altered by oxytocin. Taken together, these 3 studies will provide most of the 
information required to support larger clinical studies to be proposed in the P01 
application. 
RATIONALE 
 
Nearly all clinical studies of oxytocin involve intranasal administration, which 
results in minimal or no increase in circulating oxytocin concentration, but effects that 
are presumed to reflect actions in the brain.  The focus of most of these studies involves 


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presumed social effects of oxytocin, typically measured by brain activity or subjective 
report when viewing images of differing social valence.  These studies universally show 
an effect of oxytocin, although their rigor has been questioned because of extremely 
small sample size and lack of a priori statistical analysis plan [16].  Most studies 
demonstrate small effects of oxytocin close to a threshold P value of 0.05 for statistical 
significance, and these measures can typically only be assessed once, requiring a 
between subject design inappropriate to pharmacokinetic-dynamic modeling.  For these 
reasons we do not plan to use these kinds of outcome measures to assess central 
effects of oxytocin. 
 
This protocol focuses on two measures of autonomic control, both in use in 
current studies by our group, to quantify central actions of oxytocin.  First, we propose 
to examine the influence of oxytocin on heart rate variability with focus on its effect on 
high frequency variability, most commonly ascribed to parasympathetic nervous system 
activity acting to brake sympathetic tone.  Intranasal oxytocin has been demonstrated to 
have a large effect size on this measure which can be repeated at frequent intervals [7]. 
As a secondary assessment of parasympathetic activity, we will measure high 
frequency fluctuation in pupil diameter, termed hippus, which also reflects 
parasympathetic nervous system activity [14].  This outcome measure can be assessed 
in 3 seconds using equipment currently being used under IRB approved protocols. 
 
  
 
 


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Protocol 
Effects of intramuscular oxytocin on pupil diameter and heart rate 
variability 
 
PRIMARY GOAL:  Provide an estimate of effect size of intramuscular oxytocin on tests of 
parasympathetic nervous system activity using variations in pupil diameter and in heart 
rate. 
 
GENERAL METHODS:  Equal numbers of healthy adult men and women will be recruited 
(22 total) and will have 2 visits in the Pain Research Unit at Piedmont Plaza 2.  A non-
invasive, chest band heart rate monitor will be applied and baseline pupil diameter 
measures obtained with a pupilometer.  Subjects will receive an intramuscular injection 
of either oxytocin (Pitocin®), 10 IU, or saline.  The study will be randomized and double 
blind and all subjects will receive both treatments. 
 
STUDY DESIGN 
Inclusion Criteria: We request permission to study up to 30 subjects so that we will 
have 22 evaluable subjects who have completed both visits. 
1. Male or female > 18 and < 66 years of age, Body Mass Index (BMI) <40. 
2. Generally in good health as determined by the Principal Investigator based on 
prior medical history, American Society of Anesthesiologists physical status I or II 
3. Normal blood pressure (systolic 90-140 mmHg; diastolic 50-90 mmHg) resting 
heart rate 45-100 beats per minute) without medication 
4. Female subjects of child-bearing potential and those < 1 year post-menopausal, 
must be practicing highly effective methods of birth control such as hormonal methods 
(e.g., combined oral, implantable, injectable, or transdermal contraceptives), double 
barrier methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal 
jellies or cream), or total abstinence from heterosexual intercourse for a minimum of 1 
full cycle before study drug administration. 
5. All subjects must be vaccinated against SARS-CoV-2, with proof via vaccination 
card or the NC HHS form. 
 


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Exclusion Criteria: 
 
1. Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin® 
2. 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 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 
3. Women who are pregnant (positive result for urine pregnancy test at screening 
visit), women who are currently nursing or lactating, women that have been pregnant 
within 2 years. 
4. Subjects with neuropathy, chronic pain, diabetes mellitus, or taking 
benzodiazepines or pain medications on a daily basis. 
5. Subjects with history of eye surgery, with cataracts, or taking medications for eye 
conditions. 
 
Study Visit 1:  The participant will report to Piedmont Plaza 2. The participant 
will review and sign the Informed Consent. After informed consent is adequately 
obtained, a detailed medical history will be obtained from the participant, female 
participants will provide a urine sample to determine pregnancy status.  The research 
nurse will have the subject place the chest belt for heart rate monitoring, familiarize the 
subject with the pupilometer, and calibrate the system for gaze by having the subject 
look at each of 9 gray Xes on a monitor located in front of the chin rest and pupilometer 
camera. 
Baseline blood pressure, heart rate and respiratory rate will be measured. Pupil 
diameter measurements will be obtained for 20 seconds every 5 minutes for 20 
minutes. The subject will only need to position their head with chin on the chin rest 
during times of pupil measurements.  During the pupil measurements we will record the 
measurements using an infrared camera.   
 
The subject will then receive an intramuscular injection of oxytocin (Pitocin®), 10 
IU or the same volume (1 ml) of saline.  Pupil measurements will be made for 20 
seconds every 5 minutes until 120 minutes after study drug administration. 


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Study Visit 2 
 
All procedures from Study Visit 1 will be repeated with the cross-over study drug 
solution. The visits will be at least 24 hours apart. 
 
Safety and Monitoring:  Given that oxytocin is available over the counter in much larger 
systemic doses than proposed in this application and since multiple scientific reports 
have examined much larger systemic doses than in this application using only 
subjective reporting, we propose to only request subjects to report any unusual 
sensations and query them at the end of each drug administration study day if they 
experienced any unusual sensations. Blood pressure, heart rate and respiratory rate will 
be measured at both study visits at baseline and then at 30, 60, and 90 minutes after 
the injection. 
RISKS 
 
Risks of intramuscular injection include pain and bruising.  Risks of oxytocin are 
primarily restricted to uterine contraction in the presence of pregnancy, since oxytocin 
receptors are not present in the non-pregnant uterus (Package insert attached). 
Additionally we noted in our previous study of intravenous oxytocin there is the 
possibility of a feeling of being flushed, headache and increased heart rate with no 
significant change in blood pressure during or immediately after the infusion. These 
events were reported by previous participants in the intravenous study, but were short 
lived, lasting approximately 12-15 minutes. We have received no reports of these 
effects in our current study of intramuscular oxytocin. The use of infrared video camera 
will does not expose participants to a greater amount of light than expected in normal 
use of an infrared camera. 
Data Safety Monitoring Plan 
 
Although the use of oxytocin in this protocol is outside FDA approval for oxytocin 
administration during the postpartum period, the dose to be studied is similar to or less 
than that of multiple recent studies in healthy volunteers with intranasal oxytocin 
purchased over the counter in the US [1-6; 8-13; 15-19] and without description of 


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adverse events.  For these reasons, we do not propose a data safety monitoring 
committee or special safety evaluation beyond those required by IRB regulations. 
Minority, Gender, and Children Participation 
Both sexes and races and ethnicities will be actively recruited in this small study.  
Children under age 18 are not included in these protocols because this protocol 
because the safety of this product has not been established in children.  
 
Volunteer Payment 
Participants will be paid a total of $200 according to the following payment 
schedule which we have used throughout the last 2 cycles of this grant's protocols. We 
believe that this payment schedule is fair and appropriate, paying for each procedure 
attempted and an additional payment for completion of the entire study.  
Completion of study visit 1: $50 
Completion of study visit 2: $150 
Long-term Follow-up 
Volunteers will be contacted one and 7 days after the last study visit and 
questioned about adverse events from the study. 
 
Data Share Plan Stanford Pilot Data   
Scope of Work:  The Dr. Steven Shafer at Stanford University will establish and direct 
a pharmacokinetic/dynamic (PK/PD) modeling to facilitate future modeling in a NIH 
grant to be funded late 2021/early 2022. The PK/PD modeling will generate a 
mathematical model of oxytocin uptake, distribution, and elimination following 
intravenous delivery in humans. The PK/PD Core will use these mathematical models to 
describe the relationship between concentration at the site of effect and therapeutic 
response. The models will facilitate dosing regimens for future studies.  The dose effect 
of intramuscular oxytocin will be modeled by the relationship noted on pupil diameter 
and heart rate variability and pupillary hippus measurements. 
 
 
 


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STATISTICAL RATIONALE 
Co-Primary outcome measures are magnitude of power at the dominant frequency in 
the Fourier transform of pupil diameter in the .1-2 Hz range, termed hippus, and heart 
rate variability in the high frequency range (HF-HRV).  These are complementary 
measures which are both affected by parasympathetic nervous system activity and by 
non-overlapping other factors.  We request a convenience sample of 22 subjects for the 
purpose of preliminary data to provide variance and effect size estimates that will inform 
federal grant submission for use of this model to a larger sample size to adequately test 
the plasma concentration response of computer controlled infusions of oxytocin to 
targeted plasma concentrations with intravenous infusions.  Thus, we propose 
descriptive statistics as the primary analysis of this pilot study.  
 
 
 
[1] Gossen A, Hahn A, Westphal L, Prinz S, Schultz RT, Grunder G, Spreckelmeyer KN. 
Oxytocin plasma concentrations after single intranasal oxytocin administration - a study 
in healthy men. Neuropeptides 2012;46(5):211-215. 
[2] Kessner S, Sprenger C, Wrobel N, Wiech K, Bingel U. Effect of oxytocin on placebo 
analgesia: a randomized study. JAMA 2013;310(16):1733-1735. 
[3] Lee MR, Scheidweiler KB, Diao XX, Akhlaghi F, Cummins A, Huestis MA, Leggio L, 
Averbeck BB. Oxytocin by intranasal and intravenous routes reaches the cerebrospinal 
fluid in rhesus macaques: determination using a novel oxytocin assay. Molecular 
psychiatry 2017. 
[4] Leknes S, Wessberg J, Ellingsen DM, Chelnokova O, Olausson H, Laeng B. Oxytocin 
enhances pupil dilation and sensitivity to 'hidden' emotional expressions. SocCogn 
AffectNeurosci 2013;8(7):741-749. 
[5] Liu R, Yuan X, Chen K, Jiang Y, Zhou W. Perception of social interaction compresses 
subjective duration in an oxytocin-dependent manner. eLife 2018;7. 
[6] Mameli S, Pisanu GM, Sardo S, Marchi A, Pili A, Carboni M, Minerba L, Trincas G, Carta 
MG, Melis MR, Agabio R. Oxytocin nasal spray in fibromyalgic patients. Rheumatology 
international 2014;34(8):1047-1052. 
[7] Norman GJ, Cacioppo JT, Morris JS, Malarkey WB, Berntson GG, Devries AC. Oxytocin 
increases autonomic cardiac control: moderation by loneliness. Biological psychology 
2011;86(3):174-180. 
[8] Quintana DS, Westlye LT, Alnaes D, Kaufmann T, Mahmoud RA, Smerud KT, Djupesland 
PG, Andreassen OA. Low-dose intranasal oxytocin delivered with Breath Powered 
device modulates pupil diameter and amygdala activity: a randomized controlled 
pupillometry and fMRI study. Neuropsychopharmacology 2019;44(2):306-313. 


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[9] Rash JA, Campbell TS. The effect of intranasal oxytocin administration on acute cold pressor 
pain: a placebo-controlled, double-blind, within-participants crossover investigation. 
Psychosom Med 2014;76(6):422-429. 
[10] Rash JA, Toivonen K, Robert M, Nasr-Esfahani M, Jarrell JF, Campbell TS. Protocol for a 
placebo-controlled, within-participants crossover trial evaluating the efficacy of 
intranasal oxytocin to improve pain and function among women with chronic pelvic 
musculoskeletal pain. BMJ open 2017;7(4):e014909. 
[11] Striepens N, Kendrick KM, Hanking V, Landgraf R, Wullner U, Maier W, Hurlemann R. 
Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal 
administration in humans. SciRep 2013;3:3440. 
[12] Tanaka A, Furubayashi T, Arai M, Inoue D, Kimura S, Kiriyama A, Kusamori K, Katsumi 
H, Yutani R, Sakane T, Yamamoto A. Delivery of Oxytocin to the Brain for the 
Treatment of Autism Spectrum Disorder by Nasal Application. Molecular pharmaceutics 
2018;15(3):1105-1111. 
[13] Tracy LM, Labuschagne I, Georgiou-Karistianis N, Gibson SJ, Giummarra MJ. Sex-specific 
effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, 
placebo-controlled cross-over study. Psychoneuroendocrinology 2017;83:101-110. 
[14] Turnbull PR, Irani N, Lim N, Phillips JR. Origins of Pupillary Hippus in the Autonomic 
Nervous System. Investigative ophthalmology & visual science 2017;58(1):197-203. 
[15] Tzabazis A, Kori S, Mechanic J, Miller J, Pascual C, Manering N, Carson D, Klukinov M, 
Spierings E, Jacobs D, Cuellar J, Frey WH, 2nd, Hanson L, Angst M, Yeomans DC. 
Oxytocin and Migraine Headache. Headache 2017;57 Suppl 2:64-75. 
[16] Walum H, Waldman ID, Young LJ. Statistical and Methodological Considerations for the 
Interpretation of Intranasal Oxytocin Studies. Biol Psychiatry 2016;79(3):251-257. 
[17] Wang YL, Yuan Y, Yang J, Wang CH, Pan YJ, Lu L, Wu YQ, Wang DX, Lv LX, Li RR, 
Xue L, Wang XH, Bi JW, Liu XF, Qian YN, Deng ZK, Zhang ZJ, Zhai XH, Zhou XJ, 
Wang GL, Zhai JX, Liu WY. The interaction between the oxytocin and pain modulation 
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[18] Zhang H, Wu C, Chen Q, Chen X, Xu Z, Wu J, Cai D. Treatment of Obesity and Diabetes 
Using Oxytocin or Analogs in Patients and Mouse Models. PLOS ONE 
2013;8(5):e61477. 
[19] Zunhammer M, Geis S, Busch V, Greenlee MW, Eichhammer P. Effects of intranasal 
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ICF_000.pdf: 
NCT04105998
Title:  Effects of Intramuscular Oxytocin on Pupil Diameter and Heart Rate Variability 
Date: 8/31/21


Page 1 of 10
Adult Consent Form
 8/18/2021
Department of Anesthesiology
Effects of intramuscular oxytocin on pupil diameter and heart rate variability 
in healthy volunteers 
Informed Consent Form to Participate in Research
James C. Eisenach, M.D., Principal Investigator
SUMMARY
You are invited to participate in a research study. The purpose of this research is to evaluate the 
effects of oxytocin (naturally occurring hormone) given by an intramuscular (IM; into the 
muscle) injection, has on your parasympathetic nervous system. The parasympathetic nervous 
system is the part of the involuntary nervous system that is sometimes called the “rest and 
digest” system; the parasympathetic system conserves energy as it slightly slows the heart rate, 
increases intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal 
tract.  You are invited to be in this study because you are a healthy subject. Your participation in 
this research will involve 2 study visits. 
Participation in this study will involve receiving IM administration of oxytocin and we will 
record changes in your pupil size by using an infrared camera for video recording of your pupil. 
All research studies involve some risks.  A risk to this study that you should be aware of is 
discomfort from the IM injection.  There is not the possibility that you may benefit from 
participation in this study.  
Your participation in this study is voluntary.  You do not have to participate in this study if you 
do not want to.  This is not a treatment study and there are no additional choices. You will not 
lose any services, benefits, or rights you would normally have if you choose not to participate. 
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions if you need help deciding whether to join the 
study. The person in charge of this study is James C. Eisenach, M.D. If you have questions, 
suggestions, or concerns regarding this study or you want to withdraw from the study his/her 
contact information is:  James C. Eisenach, M.D.
   
   
   
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board at 3
 or the Research Subject 
Advocate at Wake Forest at 
.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


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Adult Consent Form
 8/18/2021
INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because you are a healthy adult. Your participation is voluntary. Please take your time in 
making your decision as to whether or not you wish to participate. Ask your study doctor or the 
study staff to explain any words or information contained in this informed consent document that 
you do not understand. You may also discuss the study with your friends and family.
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to evaluate the effects of oxytocin given by an 
intramuscular (IM) injection, has on your parasympathetic nervous systems; in particular your 
heart rate changes and pupil changes after receiving the study medication.
In this study oxytocin will be compared to placebo. A placebo is a substance, like a sugar pill, 
that is not thought to have any effect on your disease or condition. In this study you will receive 
the active study medication, oxytocin and the placebo which is not active, on different visits. On 
both visits you will receive one or the other by an IM injection.  Placebos are used in research 
studies to see if the drug being studied really does have an effect.
This study is a double-blinded, randomized, crossover study. Neither you nor the investigator 
will know which study medication you are receiving. Cross-over means that you will get both the 
Oxytocin injection and a placebo injection; the order that you receive the injections will be 
randomized.  Randomized means that you are put into a group by chance. It is like flipping a 
coin. This is done so that a fair evaluation of results can be made. This information is available to 
the researchers if needed in an emergency.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
We will enroll 22 people at this research site. In order to identify the 22 subjects needed, we may 
need to screen as many as 30 because some people will not qualify to be included in the study.
To be considered for inclusion in this study, you must have been vaccinated against SARS-CoV-
2 (COVID-19). We will request to see a copy of your verification record (vaccine card or North 
Carolina Health and Human Services printed form).
WHAT IS INVOLVED IN THE STUDY?
You will have 2 visits to the Pain Research Unit, located at Piedmont Plaza 2. Study visits1 and 2 
will each last approximately 2.5 hours.
If you take part in this study, you will have the following tests and procedures:
PROCEDURES
Vital Signs: we will monitor your blood pressure, heart rate and oxygen saturation (amount 
of oxygen in your blood).  
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


Page 3 of 10
Adult Consent Form
 8/18/2021
Laboratory Testing: female participants of child-bearing potential will have a urine 
pregnancy test to determine that they are not pregnant. 
Non-Invasive Heart Rate Monitoring: we will attach a small portable heart monitor to you 
during your visits to record your heart rate during your testing. The monitor will be placed 
around your chest with an elastic strap.
Pupillometry Testing:   we will have you sit in a comfortable chair and position your head 
so your chin is resting in a chinrest (very similar to the way an eye doctor would examine your 
eyes).  We will ask you to stay in this position for the testing.   A continuous video recording will 
be made of the size of your pupils while you are sitting with your chin in the chinrest.  This 
video recording is being done so that we can record the changes in your pupil before we 
administer the oxytocin and afterward.
Intramuscular injection of Oxytocin or Placebo: we will give you an injection of oxytocin 
or placebo into the muscle in your arm.  
Study Visit 1
You will report to the Pain Research Unit at Piedmont Plaza 2. You will review and sign the 
Informed Consent. After informed consent is adequately obtained, a detailed medical history will 
be obtained. During this visit we will measure your blood pressure, heart rate, respiratory rate, 
and we will place a clip on your finger which will measure the oxygen in your blood. Female 
participants of child-bearing potential will provide a urine sample for a pregnancy test.  The heart 
rate monitor will be placed around your chest. We will then have you sit in a chair and place 
your chin in a chinrest, we will have you maintain your focus at a computer monitor that will 
have an image of a fixed color, and once we have calibrated the system to your pupil we will 
begin a recording of your pupil.  We will have you sit with your chin in the chinrest for 20 
second intervals every 5 minutes for 20 minutes. We will then administer an IM injection into 
your arm of Oxytocin or placebo. After administration of the study medication, we will have you 
return to the chinrest every 5 minutes for 20 second intervals over a period of 120 minutes. We 
will also measure your blood pressure, heart rate, respiratory rate and oxygen saturation at 30, 
60, and 90 minutes after the injection.
Study Visit 2 
On the second visit; at least 24 hours after visit 1, you will report to the Pain Research Unit 
at Piedmont Plaza 2, and the study staff will repeat the same procedures from visit 1 and you will 
receive an injection that is opposite from the first visit. We will complete study visit 2 within 4 
weeks of study visit 1.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


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Adult Consent Form
 8/18/2021
As part of this research study, you will be videotaped.   We will only videotape the size of your 
pupils, your face or any other identifying characteristics will not be videotaped. This is being 
done so we can have a measurement of your pupils after the administration of oxytocin.  You 
understand that you may request the filming or recording be stopped at any time during the 
course of the research study and withdraw from the study at this time. You can also withdraw 
your consent to use and disclose the photograph/videotape/audiotape before it is used. You 
should also understand that you will not be able to inspect, review, or approve the videotapes or 
other media (including articles containing such) before they are used in this study. 
Please choose one of the following regarding the use and disclosure of the videotape used in this 
research study:
_____ I would like the videotapes of me to be destroyed once their use in this study is finished.
____ The videotapes of me can be kept for use in future studies provided they are kept secure 
and any future study will be reviewed by an IRB.   I understand that I will not be able to inspect, 
review or approve their future use.
HOW LONG WILL I BE IN THE STUDY?
You will be in the study for 2 visits. 
We will call you at days 1 and 7 after your study visits and ask about any events you experience 
after the study.
You can stop participating at any time. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. 
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. Risks and side effects related to the oxytocin we are studying include:
Oxytocin
Oxytocin is approved by the Food and Drug Administration (FDA) for use in the dose and route 
of administration we are using. We will monitor you for many theoretical problems such as 
changes in your blood pressure, how fast your heart is beating, and your urge to breathe. 
There is the possibility of a feeling of being flushed (warm feeling), headache and increased 
heart rate with no significant change in blood pressure during or immediately after the injection. 
These events have been reported by participants in a previous study of oxytocin given by 
intravenous administration. The events were short lived, lasting approximately 12-15 minutes. 
Pupillometry
The use of infrared video camera will not expose you to a greater amount of light than expected 
in normal use of an infrared camera.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


Page 5 of 10
Adult Consent Form
 8/18/2021
In addition, there is a slight risk of a breach of confidentiality.  We will do our best to protect 
your confidential information.  There also may be other side effects that we cannot predict. You 
should tell the research staff about all the medications, vitamins and supplements you take and 
any medical conditions you have. This may help avoid side effects, interactions and other risks.
Intramuscular injection
The intramuscular injection may be uncomfortable and cause a stinging sensation. You may have 
a small bruise at the injection site.
Placebo
 There is no risk associated with the placebo injection.
Taking part in this research study may involve providing information that you consider 
confidential or private.  Efforts, such as coding research records, keeping research records secure 
and allowing only authorized people to have access to research records, will be made to keep 
your information safe.
Reproductive Risks and other Issues to Participating in Research
Due to unknown risks and potential harm to the unborn fetus, sexually active women of 
childbearing potential must use a reliable method of birth control while participating in this 
study. Reliable methods of birth control are: abstinence (not having sex), oral contraceptives, 
intrauterine device (IUD), DepoProvera, tubal ligation, or vasectomy of the partner (with 
confirmed negative sperm counts) in a monogamous relationship (same partner). An acceptable, 
although less reliable, method involves the careful use of condoms and spermicidal foam or gel 
and/or a cervical cap or sponge. We encourage you to discuss this issue further with your 
physicians if you have any questions.
Pregnant women are excluded from participation in this study. Because some methods of birth 
control are not 100% reliable, a pregnancy test is required at least 10 days from your last normal 
menstrual period, if you are a sexually active woman of childbearing potential.
 ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
You are not expected to receive any direct benefit from taking part in this research study. We 
hope the information learned from this study will benefit other people in the future.
WHAT OTHER CHOICES ARE THERE?
This is not a treatment study. Your alternative is to not participate in this study.
WHAT ARE THE COSTS?
All study costs, including any study medications and procedures related directly to the study, will 
be paid for by the study. Costs for your regular medical care, which are not related to this study, 
will be your own responsibility.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


Page 6 of 10
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WILL YOUR RESEARCH RECORDS BE CONFIDENTIAL?
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals.  Your identity and/or your personal health information will not be disclosed 
unless it is authorized by you, required by law, or necessary to protect the safety of yourself or 
others.  There is always some risk that even de-identified information might be re-identified. 
Participant information may be provided to Federal and other regulatory agencies as required.  
The Food and Drug Administration (FDA), for example, may inspect research records and learn 
your identity if this study falls within its jurisdiction.
WILL YOU BE PAID FOR PARTICIPATING?
You will be paid $200 if you complete all the scheduled study visits. If you withdraw for any 
reason from the study before completion you will be paid as follows:   
Completion of study visit 1: $50
Completion of study visit 2: $150
To receive payment, you must provide your social security number, name and address so that we 
can comply with IRS (Internal Revenue Service) reporting requirements.  When payments are 
reported to the IRS we do not let them know what the payment is for, only that you have been 
paid.  If you do not wish to provide this information you can still take part in this study but you 
will not be paid.
The findings from this research may result in the future development of products that are of 
commercial value. There are no plans to provide you with financial compensation or for you to 
share in any profits if this should occur.
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by the Department of Anesthesiology at Wake Forest School of 
Medicine. The sponsor is providing money or other support to Wake Forest University Health 
Sciences to help conduct this study. The researchers do not, however, hold a direct financial 
interest in the sponsor or the product being studied.
WHAT HAPPENS IF YOU EXPERIENCE AN INJURY OR ILLNESS AS A 
RESULT OF PARTICIPATING IN THIS STUDY?
Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance 
coverage for the usual and customary medical fees for reasonable and necessary treatment of 
such injuries or illnesses. To the extent research insurance coverage is available under this policy 
the reasonable costs of these necessary medical services will be paid, up to a maximum of 
$25,000. Wake Forest University Baptist Medical Center holds the insurance policy for this 
coverage. It provides a maximum of $25,000 coverage for each claim and is limited to a total of 
$250,000 for all claims in any one year. The Wake Forest University School of Medicine, and 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


Page 7 of 10
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the North Carolina Baptist Hospitals, Incorporated do not assume responsibility to pay for these 
medical services or to provide any other compensation for such injury or illness. Additional 
information may be obtained from the Medical Center’s Director of Risk and Insurance 
Management, at 
.
If you are injured, the insurer may require information such as your name, social security 
number, and date of birth in order to pay for your care.  This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call James Eisenach at 
 or after hours 
you should call the study coordinator at 
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you about your health or behaviors 
is considered Protected Health Information. The information we will collect for this research 
study includes: medical history and medication history.
If this research study involves the diagnosis or treatment of a medical condition, then Protected 
Health Information collected from you during this study may be placed in your medical record, 
and may be used to help treat you, arrange payment for your care, or assist with Medical Center 
operations. 
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. 
Your personal health information and information that identifies you (“your health information”) 
may be given to others during and after the study. This is for reasons such as to carry out the 
study, to determine the results of the study, to make sure the study is being done correctly, to 
provide required reports and to get approval for new products.  
Some of the people, agencies and businesses that may receive and use your health information 
are the research sponsor; representatives of the sponsor assisting with the research; investigators 
at other sites who are assisting with the research; central laboratories, reading centers or analysis 
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA) or the Office of Human Research Protections (OHRP), 
the Department of Health and Human Services (DHHS) and similar agencies in other countries.  
Some of these people, agencies and businesses may further disclose your health information. If 
disclosed by them, your health information may no longer be covered by federal or state privacy 
regulations.  Your health information may be disclosed if required by law. Your health 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


Page 8 of 10
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information may be used to create information that does not directly identify you. This 
information may be used by other researchers. You will not be directly identified in any 
publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable.
Any Protected Health Information collected from you in this study that is maintained in the 
research records will be kept for an indeterminate period of time. This authorization does not 
expire. You will not be able to obtain a copy of your Protected Health Information in the 
research records until all activities in the study are completely finished. 
You can tell Dr. James C. Eisenach that you want to take away your permission to use and share 
your Protected Health Information at any time by sending a letter to this address:
James C. Eisenach, M.D.
  
   
  
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for this 
study.
If you choose to participate in this study, your medical record at Wake Forest University Baptist 
Medical Center will indicate that you are enrolled in a clinical trial.  Information about the 
research and any medications or devices you are being given as a participant may also be 
included in your medical record.  This part of the medical record will only be available to people 
who have authorized access to your medical record.  If you are not a patient at this Medical 
Center, a medical record will be created for you anyway to ensure that this important information 
is available to doctors in case of an emergency.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the results.  You can search this Web site at any time. 
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study 
participants. Information about your participation in the study will be placed in the NCBH 
medical record, along with any routine medical test results that were obtained at NCBH as part 
of this study. 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


Page 9 of 10
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WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
at any time. This could be because new information becomes available, you had an unexpected 
reaction, you failed to follow instructions, or because the entire study has been stopped. 
Information that identifies you may be removed from the data or specimens that are collected as 
part of this study and could be used for future research or shared with others without additional 
consent.
You will be given any new information we become aware of that would affect your willingness 
to continue to participate in the study.
This study will be enrolling students from the Wake Forest University Medical Center campus.  
In addition to your rights as a research participant noted in the previous section, as a student, you 
are under no obligation to participate in this study. You may refuse to participate or withdraw 
from the study at any time and for any reason without affecting your grades, performance 
evaluations, or assignments. You will not be pressured into participating in this research study by 
any statements or implied statements that your grades, performance evaluations or assignments 
will be affected by your willingness to enroll in the study. Your medical records/information will 
not be used by the faculty, administration or study staff to make decisions regarding the status of 
your medical benefits. If you have questions regarding your enrollment in the study and your 
status as a medical student, please contact the Office of Student Services for additional 
information.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or in the event of a research-related injury, contact the study 
investigator, Dr. James Eisenach at 
 or after hours you should call the study 
coordinator by calling 
.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
 or the 
Research Subject Advocate at 
.
You will be given a copy of this signed consent form. 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022


Page 10 of 10
Adult Consent Form
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SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form.  If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me.  I have had a chance to 
ask questions about being in this study and have those questions answered.   By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):_____________________________
Subject Signature: _________________________________ Date: ________Time:_______ am pm 
Person Obtaining Consent (Printed):_____________________________
Person Obtaining Consent: ______________________________________
 
Date: ________Time:_______ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00060838
Meeting Date Approved 8/31/2021          
Version Valid Until: 7/12/2022