Clinical trial NCT03935399
Conditions: Chronic Pain
Sponsor: Wake Forest University Health Sciences
Start date: 2019-08-08; Completion date: 2020-04-30
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This study proposes to evaluate the effects that a dose of oxytocin given by intramuscular (IM) injection (into the muscle) will have on an area of skin that has been exposed to ultraviolet (UV) light. The area of skin exposed to UV light will have a mild sun burn feeling.

Sensory testing will be performed on the area of UV burn. The area will be evaluated for sensitivity in 3 methods: touch, vibratory

Detailed description:
This protocol aims to provide an estimate of effect size of intramuscular oxytocin on a test of Aβ and of Aδ fiber sensitivity in injured skin following ultraviolet B (UVB) burned skin.

For the primary goal - to examine the effects of oxytocin peripheral nerves after tissue injury - the investigators chose the controlled ultraviolet sunburn model.

The investigators propose a randomized, blinded, cross over design with treatment with oxytocin one day and placebo on another. Following baseline measures on each of the two study days, participants will receive an intramuscular injection of oxytocin (Pitocin®) in its indicated dose of 10 IU (17 μg) or an equivalent volume of saline.

In order to determine the highest frequency that Aβ nerve fibers can respond to, the investigators will use a device that produces an oscillatory / vibratory stimulus which can be used on the hand.

Pain threshold to punctate stimulation within the area of irradiation will be determined using calibrated von Frey filaments and an up-down sequential method which efficiently estimates median thresholds.

Thermal heat testing will also be performed by the surface of the skin of the forearm or leg is heated to 45°C using a computer controlled thermode for a period of 5 minutes.

Arms: arm 1: Intramuscular injection of oxytocin (Pitocin®), 10 IU on the first study day and of 1 ml saline placebo on the second study day arm 2: Intramuscular injection of 1 ml saline placebo on the second study day and of oxytocin (Pitocin®), 10 IU on the second study day
Interventions: intervention 1: Oxytocin intervention 2: Saline
Intervention descriptions: intervention 1: 10 IU oxytocin (Pitocin) for intramuscular injection intervention 2: 1.5 ml preservative free saline for intramuscular injection

Protocol documents:
Prot_SAP_001.pdf: 
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Effects of intramuscular oxytocin on sensory function in healthy 
volunteers with ultraviolet burn injury to the skin 
      IRB00056660 
NCT03935399 
      Version Date: 10/17/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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.  The goal of this IRB protocol is to test whether effects 
of oxytocin on peripheral nerves observed in physiology experiments in rodents might 
be applicable to humans and worthy of study more completely in the NIH P01 
application in September, 2019.     
 
ANIMAL DATA SUPPORTING THE UNDERLYING PREMISE 
 
Following acute peripheral injury and in many chronic pain states there are 
changes in sensory response to mechanical stimulation in and surrounding areas of 
pain.  Patients and investigators focus understandably on hypersensitivity, resulting in 
increased pain to a normally painful stimulus (hyperalgesia) and pain from light touch 
which is normally not painful (allodynia).  Yet, hyposensitivity is as or more prevalent in 
chronic neuropathic pain, and many chronic pain patients experience both hyper- and 
hyposensitivity [9; 19; 24].  Gate control theory posits that Aβ, touch sensitive fiber input 
acts to reduce Aδ and C nociceptor input [18], so loss of Aβ input could play an 
important role in the setting of pain. 
 
Over the past 7 years we have recorded from Aβ and Aδ neurons in vivo, 
showing that both are altered after injury and that oxytocin acutely returns their function 
towards normal [2; 4-6; 23].  Within minutes of peripheral skin incision, during recovery 
from surgery, and in a model of chronic nerve injury pain, Aδ are sensitized, as 
evidenced by larger receptive fields, lower mechanical threshold in the receptive field for 
activation, shift in response to a tonic mechanical stimulus from a rapidly adapting, on-


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off response to a sustained or slowly adapting response, and ability to respond to 
repeated stimuli at higher frequency than before.  In contrast, opposite effects are seen 
in the Aβ touch-sensitive neurons, with smaller or non-existent receptive fields, higher 
mechanical threshold for activation, hyperpolarized resting membrane potential (Em), 
and reduction in the frequency of stimuli they can respond to.  Experimental constraints 
precluded the study of all of these outcomes during acute peripheral oxytocin exposure, 
but oxytocin depolarizes Em in Aβ fibers towards normal by hyperpolarizing Em in Aδ 
fibers, which should render them less responsive to peripheral stimuli. 
 
In summary, these animal data support the concept that oxytocin may act in the 
periphery to reset the balance of touch and nociceptor mechanical input towards normal 
after injury.  They suggest that treatment of oxytocin in humans with peripheral injury 
will affect touch-sensitive Aβ fibers by restoring their response to high frequency, 
vibration stimuli and will reduce the sensitivity of Aδ nociceptors, thereby increasing the 
pain detection threshold for mechanical stimuli. 
 
RATIONALE FOR USE OF THE UV-BURN PLUS HEAT MODEL OF PERIPHERAL INJURY 
 
For our primary goal – to examine the effects of oxytocin peripheral nerves after 
tissue injury – we chose the controlled ultraviolet sunburn model.  This is a model that 
we have previously used at Wake Forest in healthy volunteers [8].  It utilizes an FDA 
approved device which is designed and marketed to evaluate sunscreens in people, is 
titrated to the individual’s response to UV radiation, and results in a subscribed area of 
redness and sensitivity to light touch that lasts 2-3 days, with minimal or no 
spontaneous pain and no lasting changes in the skin.  The area of sensitivity can be 
expanded beyond the area of UV radiation exposure temporarily by heating the area 
with a non-painful stimulus (40°C) for 5 min, and this expanded area and sensitivity 
within the area of UV exposure can be maintained by repeating this heating at 40 min 
intervals. As in our previous use of this method and as used by others [8; 16], we 
propose to expose the skin to 3 levels of irradiation to determine the minimum 
erythematous dose (MED) defined on inspection the following day characterized by 
marked redness with well demarcated borders [1].  On a subsequent day the skin on the 
volar aspect of the dominant wrist will be irradiated at the 2 MED dose and the subject 


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will return twice for testing, first on the day after irradiation and second the following 
day. At each testing session the area of UV radiation will be heated to 40°C twice 
separated by 40 minutes. 
 
RANDOMIZED TREATMENT 
 
We propose to take advantage of the stable nature of this model of peripheral 
injury for 2-3 days in order to apply a randomized, blinded, cross over design with 
treatment with oxytocin one day and placebo on another.  Following baseline measures 
on each of the two study days, subjects will receive an intramuscular injection of 
oxytocin (Pitocin®) in its indicated dose of 10 IU (17 μg) or an equivalent volume of 
saline.  In the absence of pregnancy or the postpartum period, doses of oxytocin much 
greater than this (24-80 IU) produces no physiologic adverse effects when administered 
intranasally, which produces rapid systemic absorption [15; 17; 21; 27; 32]. 
 
RATIONALE FOR PRIMARY OUTCOME MEASURES AND TIMING OF MEASUREMENTS 
 
We will determine thresholds to perception of vibration at a frequency of 256 Hz, 
pain within the area of UV burn, and area of hypersensitivity to von Frey filament testing 
before and at the following times after intramuscular study drug injection: 5 minutes, 45 
minutes, and 65 minutes. We will also perform a vibration threshold at 30 minutes after 
the intramuscular injection.  These primary outcome measures will assess both Aβ and 
Aδ/C fiber sensitivity in the area of injury and these times will capture the time of peak 
plasma oxytocin concentration after intramuscular injection [20]. 
TEST OF Aβ FIBER SENSITIVITY 
 
Light touch is subserved by a group of myelinated peripheral nerves with fast 
conduction in the Aβ range and which are capable of following high frequencies, being 
responsible for the sensation of vibration.  This capability of individual nerve fibers to 
respond with high frequency also underlies our ability to sense a light touch moving 
across the body surface as in brushing. 
 
As noted, preclinical studies show that following injury these light touch fibers 
become less sensitive to repeated stimulation as occurs with a vibration [2].  Oxytocin, 


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when perfused around the neuronal cell bodies of these Aβ nerve fibers, partially 
restores their function, including their sensitivity to low intensity stimulation. 
 
In order to determine the threshold for perception of vibration, we have created a 
simple device that produces an oscillatory / vibratory stimulus which can be used on the 
skin.  The subject places the area of interest on the device and the device is set to 
slowly increase the intensity of vibration at 256Hz until the subject first perceives this. 
This is repeated twice in the areas of interest.  More details on the device are provided 
in the Appendix. 
 
We anticipate that oxytocin will have no effect on normal Aβ fibers with testing in 
normal skin but will decrease the detection threshold for vibration intensity towards 
normal in the area of UV radiation exposure . 
TEST OF Aδ FIBER SENSITIVITY 
 
Pain threshold to punctate stimulation within the area of irradiation will be 
determined using calibrated von Frey filaments and an up-down sequential method 
which efficiently estimates median thresholds [7]. 
 
SECONDARY OUTCOME MEASURE: SUSTAINED HEAT 
 
As part of a protocol used by us in several studies, the surface of the skin of the 
forearm opposite to the area of irradiation is heated to 45°C using an FDA approved, 
Peltier-controlled thermode for a period of 5 minutes (TSA®, Medoc, Ramat Yishai, 
Israel).  This typically results in a slowly increasing pain experience, peaking at 5 
minutes in the mild to low moderate range and has been tolerated by more than 150 
subjects in studies over the past 14 years. 


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In an interim analysis of an ongoing clinical study 
in volunteers, we noted that spinal injection of oxytocin, 
15 μg (equivalent to 9 IU), that pain from this sustained 
heat was dramatically reduced over the 5 minutes of 
stimulus presentation (figure). In contrast, spinal 
oxytocin had no effect on the stimulus-response 
relationship of pain to noxious heat over a 42-50°C 
range when the stimuli were presented for only 5 
seconds.  These data suggest that oxytocin reduces C-
fiber mediated signaling of sustained heat pain, likely 
through a spinal site of action.  
 
Drugs administered spinally have a much higher 
concentration in cerebrospinal fluid than plasma.  Nonetheless, spinally administered 
drugs are typically absorbed to an extent and with a time course similar to that after 
intramuscular injection, and it is conceivable that the effect on sustained heat pain we 
are seeing in the spinal study reflect peripheral effects via systemic absorption.  Thus, if 
we see a similar reduction in response to sustained heat in this protocol of 
intramuscular administration, we will conclude that oxytocin is more likely activing 
peripherally than spinally. 
 
 


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Protocol 
Effects of intramuscular oxytocin on sensory function in healthy 
volunteers with ultraviolet burn injury to the skin 
 
PRIMARY GOAL:  Provide an estimate of effect size of intramuscular oxytocin on a test of 
Aβ and of Aδ fiber sensitivity in injured skin following ultraviolet B burned skin. 
 
GENERAL METHODS:  Equal numbers of healthy adult men and women will be recruited 
(ten total) and will have 5 visits in the Clinical Research Unit (CRU) at Wake Forest 
Baptist Medical Center or Piedmont Plaza 2.  In the first visit they will be trained in the 
experimental procedures to assess pain and perception of vibration and they will 
receive 3 ultraviolet radiation exposures on the calf of differing intensities surrounding 
the anticipated minimal erythematous dose (MED).  They will return one day later for 
examination of these sites and determining the MED.   At least 5 days later they will 
return, sensory tests will be repeated and ultraviolet radiation at two times the MED will 
be exposed to the volar wrist of the dominant hand.  The following day and the day 
thereafter they will return and, after heating the area of the burn to 40°C for 5 min and 
baseline sensory tests in the area of burn, they 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 12 subjects so that we will 
have 10 evaluable subjects who have completed all 5 visits. 
1. Male or female > 18 and < 60 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 
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 


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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. 
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. 
 
Study Visit 1:  The participant will report to the CRU or 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 train the participants to estimate pain quantitatively using a 2 cm2 
Peltier controlled thermode (TSA®) applied to a forearm with 5 sec presentation of 
stimuli at 39, 41, 43, 45, 47, 49, and 50°C, using a 11 point numerical verbal scale 
(NRS) anchored at 0 for no pain and 10 for the worst pain imaginable . Typically, the 
participant is exposed to temperatures between 380 and 510 C using a random staircase 
method. After this training, we will ask them to report pain intensity on the 0-10 NRS 
scale every minute for 5 minutes upon exposure to a 4 cm2 Peltier controlled thermode 
at 45°C to the lateral calf.  Finally, the subject will place the palmar aspect of the wrist of 
their dominant hand on a device and report when they first perceive a sensation as the 
intensity of vibration at a fixed frequency of 256 Hz is slowly increased. We have found 


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this training session significantly reduces anxiety and variability in pain and 
hypersensitivity ratings on subsequent study days. 
Ultraviolet-B light exposure will be controlled by a commercially available solar 
simulator and dose control system that meets specifications for FDA sunscreen testing 
(Solar Light Co., Inc).  The solar simulator consists of a 150-watt xenon bulb that 
produces the full range of solar ultraviolet energy (290-400 nm) without exposing 
subjects to thermal energy.  Exposure is limited to a 3 cm2 diameter circle of skin and, 
after an individualized determination of dose, produces moderate erythema that is 
sensitive to thermal and mechanical stimulation. During this visit three areas of skin on 
the subject’s calf will be exposed to ultraviolet light for different lengths of time not to 
exceed 200 seconds.  This procedure is not painful, and this burn does not produce 
spontaneous pain as the burn injury resolves over the next several days. 
Study Visit 2 
The subject will return to the CRU or Piedmont Plaza 2  24 hours later and the 
exposed areas evaluated for UV-induced erythema.  The purpose of this procedure is to 
determine each subject’s MED, defined as the dose of UV light that produces clear 
redness with sharply demarcated borders. 
Study Visit 3  
 
The subject will report to the CRU or Piedmont Plaza 2 at least 5 days after study 
visit 2.  After determination of vibration frequency perception threshold on the dominant 
arm volar aspect of the wrist, the center of the volar aspect of the wrist will be irradiated 
with an ultraviolet exposure of 2 times the subject’s MED.  Subjects will be instructed 
that they can take acetaminophen as needed, but not NSAIDs, over the next 2 days, but 
that they should not take acetaminophen within 6 hours of study visits 4 and 5. 
Study Visit 4  
 
The subject will report to the CRU the day after Study Visit 3.  Baseline blood 
pressure, heart rate and respiratory rate will be measured. Baseline measures will be 
obtained to include 5 minute presentation of a 45°C stimulus to the lateral calf, 
perception threshold of vibration intensity on the dominant arm site of ultraviolet burn, 
and pain threshold using application of calibrated von Frey filaments to the site of 
ultraviolet burn. Finally, we will map the area of hypersensitivity surrounding the burn 


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site using a 225mN von Frey filament. 
Following baseline measurements we will 
apply the Peltier controlled thermode to the burn site and increase the probe 
temperature to 40°C for 5 min.  Immediately after removing the probe the subject will 
receive an intramuscular injection of oxytocin (Pitocin®), 10 IU or the same volume (1 
ml) of saline.  Thresholds to perception of vibration and pain within the area of UV burn 
and areas of hypersensitivity surrounding the burn area will be determined 5 minutes, 
45 minutes, and 65 minutes after injection.  A vibratory threshold will also be determined 
at 30 minutes after the injection. Pain report to a 5 minute presentation of the 45°C 
stimulus to the lateral calf will be determined at the 20 and 60 min time period after 
injection. The area of the burn site will be heated to 40°C for 5 min a second time, 40 
min after the first. 
Study Visit 5 
 
All procedures from Study Visit 4 will be repeated with the cross-over study drug 
solution. 
 
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. UV protective glasses will be worn by study staff 
administering the UV exposure. The subject will be shielded with a barrier so there will 
be no exposure to their eyes. 
Blood pressure, heart rate and respiratory rate will be measured on study visits 4 and 5 
at baseline and then at 30 and 60 minutes after the injection. 
RISKS 
 
Risks of intramuscular injection include pain and bruising.  Risks from the FDA 
approved heat stimulus device are pain, and the subject can stop testing at any time if 
the pain they perceive is such that they do not want to continue.  Please note that these 
devices are used in many pain clinics routinely and have multiple fail-safe designs to 


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avoid thermal burn.  Risks from the non-regulatory vibratory device are related only to 
microshock and are addressed in the Appendix. Risks from the Electromechanical  
Risks from the UV radiation causes mild sunburn, and may blister or hurt for a few days.  
The sunburned skin will almost always tan in normal individuals, and may tan more 
darkly than the surrounding skin for several weeks to several months. It is possible that 
the darker patches of skin may be present for up to a year. Long-term darkening 
(discoloration) or scarring is possible, but rare in people with normal skin and a history 
of normal tanning. Repeated exposure of the skin to UV light is known to produce 
photoaging (aging of the skin in response to sunlight) and carries the risk of photo 
carcinogenesis (skin cancer). However, the few exposures in this study, equivalent 
perhaps to one hour of casual sun exposure during the summer, produces an 
insignificant increase in lifetime risk. 
 
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 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 have been reported by previous 
participants but were short lived, lasting approximately 12-15 minutes. 
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 [10; 12-15; 17; 20-22; 25-32] and without 
description of 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.  
 


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Volunteer Payment 
Participants will be paid a total of $500 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: $25 
Completion of study visit 3: $25 
Completion of study visit 4: $50 
Completion of study visit 5: $350 
 
Long-term Follow-up 
Volunteers will be contacted daily within the following week after the last study 
visit and questioned about adverse events from the study. 
 
STATISTICAL RATIONALE 
Co-Primary outcome measures are the vibration intensity detection threshold, the 
punctate stimulus pain detection threshold in the burned area, and the area of 
hypersensitivity surrounding the UVB area.   We request a convenience sample of the 
remaining 5 subjects in this protocol under this amendment 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.  
 
 
 
 
 
 


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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. 
[29] Walum H, Waldman ID, Young LJ. Statistical and Methodological Considerations for the 
Interpretation of Intranasal Oxytocin Studies. Biol Psychiatry 2016;79(3):251-257. 
[30] 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, 


15 
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Wang GL, Zhai JX, Liu WY. The interaction between the oxytocin and pain modulation 
in headache patients. Neuropeptides 2013;47(2):93-97. 
[31] 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. 
[32] Zunhammer M, Geis S, Busch V, Greenlee MW, Eichhammer P. Effects of intranasal 
oxytocin on thermal pain in healthy men: a randomized functional magnetic resonance 
imaging study. Psychosom Med 2015;77(2):156-166. 
 

ICF_000.pdf: 
Page 1 of 10
Adult Consent Form
10/17/2019
Department/Section of Anesthesiology
Effects of intramuscular oxytocin on sensory function in healthy volunteers 
with ultraviolet burn injury to the skin
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 nerves and tissues after exposure to a small amount of ultraviolent 
(UV- B) radiation (mild sunburn) on your skin. You are invited to be in this study because you 
are a healthy subject. Your participation in this research will involve 5 study visits. 
Participation in this study will involve receiving thermal heat testing, exposure to a small amount 
of UV- B radiation (a mild sunburn), vibratory sensory testing and IM administration of 
oxytocin.  All research studies involve some risks.  A risk to this study that you should be aware 
of is discomfort from the thermal/sensory/UV testing and 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 
 or the Research Subject 
Advocate at Wake Forest at 
.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


Page 2 of 10
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10/17/2019
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 nerves and tissues after exposure to a small amount of 
UV- B radiation (mild sunburn) on your skin. 
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. 
Placebos are used in research studies to see if the drug being studied really does have an effect.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
We will enroll 10 people at this research site. In order to identify the 10 subjects needed, we may 
need to screen as many as 12 because some people will not qualify to be included in the study.
WHAT IS INVOLVED IN THE STUDY?
You will have 5 visits to the Clinical Research Unit (CRU) at Wake Forest Baptist Medical 
Center; study visit 1, 2, and 3 may also be conducted at Piedmont Plaza 2 in the Anesthesia Pain 
Research area. Study visit 1 will last approximately 2 hours, study visit 2 will last approximately 
30 minutes, study visit 3 will last approximately 1 hour, study visits 4 and 5 will last 
approximately 2 hours each.
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).  
Laboratory Testing: female participants of child-bearing potential will have a urine 
pregnancy to determine that they are not pregnant. 
Thermal Heat Testing: we will train you to accurately describe pain from a small (about the 
size of a penny) and a large (about the size of a half dollar) probe. The tip of the heat probe that 
will be applied to the skin on your forearm is about the size of a penny.  The tip of the heat probe 
that will be applied to your calf is about the size of a half dollar. The thermal heat probe will be 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


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Adult Consent Form
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controlled by a computer that is programmed to deliver temperatures that range from skin 
temperature up to a temperature that is hot (122 ºF) and uncomfortable, but does not burn your 
skin.
Vibratory/Sensory Testing: Oscillatory motion can be termed as the repeated motion in 
which an object repeats the same movement over and over.
UV-B Testing: we will expose small areas of your skin to a light that will give you a mild 
sunburn in small areas (about the size of a dime).
Intramuscular injection of Oxytocin: we will give you an injection of oxytocin or placebo 
into the muscle in your arm.  
Study Visit 1
You will report to the Clinical Research Unit (CRU) or 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, 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. We will 
perform thermal heat training by applying thermal temperatures that range from 100°F to 122 °F 
with a 5 second presentation of varying temperatures to your forearm. We will ask you to rate 
each stimuli using an 11 point numerical verbal scale (NRS) anchored at 0 for no pain and 10 for 
the worst pain imaginable.  After this training, we will then place a slightly larger probe on your 
lateral calf and warm the area to a temperature of 113F for 5 minutes.  During this five minute 
warming period we will ask you to give a pain rating each minute for any pain you are 
experiencing. We will touch the skin on your wrist with filaments (similar to a paint brush 
bristle) and have you tell us when they become sharp or prickly.
Finally, we will place the inside of your wrist on a device that will vibrate. We will ask you to 
tell us when you first feel the vibration or sensation. We will then expose three areas on your calf 
to the UV-B light; the areas will be about the size of a dime and will produce a small area of 
redness.
Study Visit 2 
On the second visit; 24 hours after visit 1, you will report to the CRU or Piedmont Plaza 2, 
and the study staff will look at the areas of skin that were exposed to the UV-B light and 
determine which area produced the minimal amount of redness.
Study Visit 3
You will return to the CRU or Piedmont Plaza 2 at least 5 days after study visit 2. We 
will perform the vibratory testing again on your wrist. After this testing we will expose an area of 
skin on your wrist to the UV light for 2 times the length of time that caused light reddening in the 
previous exposure to your calf in visit 1. You will return to the CRU for the following 2 days for 
additional thermal and vibratory testing.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


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Study Visit 4
You will return to the CRU the day after study visit 3. We will place the larger thermal probe on 
your calf and warm the area to a temperature of 113F for 5 minutes.  During this five minute 
warming period we will ask you to give a pain rating each minute for any pain you are 
experiencing.  We will then repeat the vibratory testing on your wrist on the arm that was 
exposed to the UV burn and we will ask you to rate the sensation you feel in the area of the UV 
burn when we touch you with different filaments (similar to a paint brush bristle).
After the baseline measurements have been completed we will apply the smaller thermal probe to 
the area on your wrist where the UV burn is, and heat the area to a temperature of 104F for 5 
minutes.  During this five minute warming period we will ask you to give a pain rating each 
minute for any pain you are experiencing. Immediately after this heating we will give you an 
injection into your arm of oxytocin or placebo.  We will repeat the vibration/sensory testing  on 
your wrist 4 more times, the filament testing 3 more times, the 113F temperature for 5 minutes 
(on the calf) 2 additional times, and the 104F temperature for 5 minutes (on the wrist) 1 more 
time after the injection.
Study Visit 5
You will return to the CRU the day after study visit 4.  We will place the slightly larger thermal 
probe on your calf and warm the area to a temperature of 113F for 5 minutes.  During this five 
minute warming period we will ask you to give a pain rating each minute for any pain you are 
experiencing. We will then repeat the vibratory testing on your wrist on the arm that was 
exposed to the UV burn and we will ask you to rate the sensation you feel in the area of the UV 
burn when we touch you with different filaments (similar to a paint brush bristle).
After the baseline measurements have been completed we will apply the smaller thermal probe to 
the area on your wrist where the UV burn is, and heat the area to a temperature of 104F for 5 
minutes.  During this five minute warming period we will ask you to give a pain rating each 
minute for any pain you are experiencing. Immediately after this heating we will give you an 
injection into your arm of oxytocin or placebo.  We will repeat the vibration/sensory testing on 
your wrist 4 more times, the filament testing 3 more times, the 113F temperature for 5 minutes 
(on the calf) 2 additional times, and the 104F temperature for 5 minutes (on the wrist) 1 more 
time after the injection.. 
HOW LONG WILL I BE IN THE STUDY?
You will be in the study for approximately 2 weeks. We will call you daily for 5 days after study 
visit 5.
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 thermal/ sensory testing and oxytocin 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


Page 5 of 10
Adult Consent Form
10/17/2019
we are studying include:
Heat Probe 
You may experience brief pain during the thermal heat testing.
Vibratory Testing
You may experience a mild vibration in fingers/hand/forearm.
UV-B
UV radiation causes mild sunburn, and may blister or hurt for a few days.  The sunburned skin 
will almost always tan in normal individuals, and may tan more darkly than the surrounding skin 
for several weeks to several months. It is possible that the darker patches of skin may be present 
on your legs for up to a year. Long-term darkening (discoloration) or scarring is possible, but 
rare in people with normal skin and a history of normal tanning.
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. We will 
treat any side effects that you may experience if the changes are enough to concern us.
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 administration. 
The events were short lived, lasting approximately 12-15 minutes.
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.
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 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


Page 6 of 10
Adult Consent Form
10/17/2019
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.
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 $500 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: $25
Completion of study visit 3: $25
Completion of study visit 4: $50
Completion of study visit 5: $350
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.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


Page 7 of 10
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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 
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 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


Page 8 of 10
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10/17/2019
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 
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.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


Page 9 of 10
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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. 
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 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020


Page 10 of 10
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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. 
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: IRB00056660
Meeting Date Approved 10/29/2019          
Version Valid Until: 4/28/2020