Clinical trial NCT01996605
Conditions: Healthy Volunteer Study
Sponsor: Wake Forest University Health Sciences
Start date: 2014-01-02; Completion date: 2022-10-10
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the effect of intrathecal oxytocin on areas and intensity of hyperalgesia and allodynia induced by topical capsaicin.

Detailed description:
Purpose: There is a strong experimental basis to support the study of oxytocin by the spinal route for analgesia in humans. Oxytocin containing cells in the dorsal parvocellular division of the paraventricular nucleus (PVN) project to the spinal cord (1). Noxious stimulation activates these cells via the A1 noradrenergic relay in the pons (2) and produces analgesia by spinal release of oxytocin, since intrathecal injection of an oxytocin receptor antagonist worsens pain behaviors from peripheral inflammation (3). Direct electrical stimulation of the PVN reduces dorsal horn neuronal responses to noxious stimulation, and this is blocked by administration of sequestering antibody for oxytocin (4). Similarly, direct electrical stimulation of the PVN reduces behavioral sensitivity in a model of chronic neuropathic pain, and this effect is blocked by an oxytocin receptor antagonist (5). Intrathecal injection of oxytocin in normal rats reduces dorsal horn neuronal responses to noxious stimuli (6) as well as behavioral responses to noxious thermal (3), mechanical (3), and chemical (7) stimuli. Finally, intrathecal injection of oxytocin in rat models of chronic pain also reduces dorsal horn neuronal responses to sensory stimulation (6) as well as behavioral responses to thermal (5) and mechanical (7) stimuli.

Rationale: We anticipate that oxytocin will be effective after spinal injection in humans against chemical induced hypersensitivity states.

Objectives: Determine the effect of intrathecal oxytocin on areas and intensity of hyperalgesia and allodynia induced by topical capsaicin.

Arms: arm 1: Oxytocin 15 mcg injected spinally arm 2: Oxytocin 150 mcg injected spinally arm 3: Preservative free normal saline injected spinally
Interventions: intervention 1: Oxytocin 15 mcg intervention 2: Oxytocin 150 mcg intervention 3: Placebo
Intervention descriptions: intervention 1: Oxytocin 15 mcg will be administered spinally intervention 2: Oxytocin 150 mcg will be administered spinally intervention 3: placebo will be administered spinally

Protocol documents:
Prot_SAP_001.pdf: 
Efficacy of Intrathecal Oxytocin  
in Human Volunteers 
 
 
 
PI: James C. Eisenach, M.D. 
 
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1/25/2022 
 
BACKGROUND 
 
 
There is a strong experimental basis to support the study of oxytocin by the spinal route 
for analgesia in humans.  Oxytocin containing cells in the dorsal parvocellular division of the 
paraventricular nucleus (PVN) project to the spinal cord (1).  Noxious stimulation activates these 
cells via the A1 noradrenergic relay in the pons (2) and produces analgesia by spinal release of 
oxytocin, since intrathecal injection of an oxytocin receptor antagonist worsens pain behaviors 
from peripheral inflammation (3).  Direct electrical stimulation of the PVN reduces dorsal horn 
neuronal responses to noxious stimulation, and this is blocked by administration of sequestering 
antibody for oxytocin (4).  Similarly, direct electrical 
stimulation of the PVN reduces behavioral sensitivity in 
a model of chronic neuropathic pain, and this effect is 
blocked by an oxytocin receptor antagonist (5).  
Intrathecal injection of oxytocin in normal rats reduces 
dorsal horn neuronal responses to noxious stimuli (6) as 
well as behavioral responses to noxious thermal (3), 
mechanical (3), and chemical (7) stimuli.  Finally, 
intrathecal injection of oxytocin in rat models of chronic 
pain also reduces dorsal horn neuronal responses to 
sensory stimulation (6) as well as behavioral responses 
to thermal (5) and mechanical (7) stimuli.   
 
Many compounds and manipulations produce 
evidence of analgesia in rodents, but most studies, 
including the ones cited for oxytocin above, rely on reflex withdrawal responses to simulation or 
electrophysiologic responses in individual cells.  As such, the relevance of these observations to 
spontaneous pain in humans is far from certain.  Two observations, however, strongly suggest 
that intrathecal oxytocin would be analgesic in humans. 
 
The first, most direct evidence, is a report from China of 608 patients with chronic low 
back pain and 369 patients with acute low back pain who received single intrathecal injections of 
oxytocin (8). Intrathecal oxytocin produced acute analgesia in both settings, with nearly 
Figure 1.  Percentage of patients 
with complete pain relief from 
intrathecal injection of oxytocin. 


Efficacy of Intrathecal Oxytocin  
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universal complete pain relief reported at doses of approximately 30 μg per injection for chronic 
low back pain and 60 μg per injection for acute low back pain (Figure 1).  Duration of analgesia 
was dose dependent, with < 1 hr analgesia from approximately 7 μg per injection and > 5 hr 
analgesia from approximately 60 μg per injection. 
The second line of evidence comes from our clinical observations in obstetric patients.  
Physical injury, whether from trauma or surgery, is recognized as an important cause of chronic 
pain, and the incidence of chronic pain after surgery ranges from 10 to 40%, depending on the 
procedure (9).  We recently completed a clinical trial of over 1200 women examining the 
incidence of chronic pain after vaginal and cesarean delivery.  Although approximately 10% of 
women had pain 2 months after delivery (10), the incidence of pain one year after delivery was 
remarkably low (95% confidence limit for pain at one year of 0.7%).  This is at least an order of 
magnitude lower than that reported from any other abdominal surgery, including superficial 
surgery like inguinal herniorrhaphy (9).  We hypothesized, based on these studies, that a factor 
which is present during pregnancy may be protective of chronic pain.  We therefore examined 
hypersensitivity in rats following a surgery (spinal nerve ligation) which is commonly used as a 
model of neuropathic pain.  To our surprise, this surgery produced similar degrees of 
hypersensitivity when performed during pregnancy than in nonpregnant animals (Figure 2).  In 
contrast to this lack of effect of pregnancy, the degree of hypersensitivity significantly 
diminished for several weeks after delivery, abruptly returning when the pups were weaned from 
Figure 2.  Withdrawal threshold drops 
similarly after spinal nerve ligation 
(SNL, a model of neuropathic pain) in 
pregnant and nonpregnant animals, but 
this hypersensitivity is alleviated after 
delivery.  Colored areas are 95% CIs. 
Figure 3.  In animals with SNL 
performed during pregnancy, withdrawal 
threshold drops abruptly when pups are 
weaned at 17 days, but when SNL is 
done on the day of delivery, withdrawal 
threshold never changes from control.   


Efficacy of Intrathecal Oxytocin  
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the dams (Figure 3).  When nerve injury surgery was performed on the same day as delivery, 
hypersensitivity never developed, mimicking the clinical trial results of a lack of chronic pain 
from surgical or vaginal delivery (Figure 3). 
We subsequently performed several studies which suggest that spinal release of oxytocin 
represents the protective factor against chronic pain after childbirth.  Intrathecal injection of the 
specific oxytocin receptor antagonist, atosiban, temporarily reverses the blockade of nerve injury 
induced hypersensitivity in the postpartum period in rats.  Similarly, intracerebroventricular 
administration of the α-adrenoceptor antagonist, phentolamine, which is known to block the 
effects of lactation on activation of oxytocin-containing neurons in the paraventricular nucleus 
(PVN) of the hypothalamus, also temporarily reverses the blockade of nerve injury induced 
hypersensitivity in the postpartum period in rats.  Finally, protection against hypersensitivity 
from nerve injury is abruptly reversed when pups are separated from dams for 24 hr, and this is 
accompanied by a large decrease in oxytocin concentration in cerebrospinal fluid.  Although we 
are currently performing more clinical and laboratory studies to further define this mechanism, 
these data suggest that spinal oxytocin receptor stimulation in the period immediately following 
delivery protects against the generation of injury-induced hypersensitivity and subsequent 
chronic pain. 
We recently completed a Phase 1 safety study of intrathecal oxytocin and observed no 
serious adverse events over the dose range studied (5-150 μg).  One subject at the 150 μg dose 
had transient subjective numbness in sacral dermatomes, but this was preceded by a vasovagal 
episode beginning just prior to spinal injection, and this did not occur in other subjects at this 
dose.  There were no objective signs of motor or sensory dysfunction in any volunteer, and blood 
pressure, heart rate, sensorium, corrected QT interval and serum sodium were unaffected. 
We anticipate that oxytocin will be effective after spinal injection in humans against 
chemical induced hypersensitivity states.  For these future studies, we will use a controlled and 
blinded study of intrathecal oxytocin against topical capsaicin, which we have used in previous 
studies under IND of spinal analgesics and which results in an area of increased pain sensation to 
a normally painful stimulus (hyperalgesia) and pain sensation to what previously was an 
innocuous stimulus (allodynia).  This model of superficial and deep neuropathic pain in humans 
can be easily studied in volunteers, as these sensations last only a few hours and are not 


Efficacy of Intrathecal Oxytocin  
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distressing.  Spinal oxytocin is effective in reducing or blocking experimentally induced 
hyperalgesia in rats, and we anticipate it will be in humans as well.   
 
References 
 
1.  Hallbeck M, Larhammar D, Blomqvist A. Neuropeptide expression in rat paraventricular 
hypothalamic neurons that project to the spinal cord. J Comp Neurol 2001;433:222-38. 
 
2.  Pan B, Castro-Lopes JM, Coimbra A. Central afferent pathways conveying nociceptive 
input to the hypothalamic paraventricular nucleus as revealed by a combination of 
retrograde labeling and c-fos activation. J Comp Neurol 1999;413:129-45. 
 
3.  Yu SQ, Lundeberg T, Yu LC. Involvement of oxytocin in spinal antinociception in rats 
with inflammation. Brain Res 2003;983:13-22. 
 
4.  Rojas-Piloni G, Lopez-Hidalgo M, Martinez-Lorenzana G, Rodriguez-Jimenez J, 
Condes-Lara M. GABA-mediated oxytocinergic inhibition in dorsal horn neurons by 
hypothalamic paraventricular nucleus stimulation. Brain Res 2007;1137:69-77. 
 
5.  Miranda-Cardenas Y, Rojas-Piloni G, Martínez-Lorenzana G, Rodríguez-Jiménez J, 
López-Hidalgo M, Freund-Mercier MJ, Condés-Lara M. Oxytocin and electrical 
stimulation of the paraventricular hypothalamic nucleus produce antinociceptive effects 
that are reversed by an oxytocin antagonist. Pain 2006;122:182-9. 
 
6.  Condes-Lara M, Maie IA, Dickenson AH. Oxytocin actions on afferent evoked spinal 
cord neuronal activities in neuropathic but not in normal rats. Brain Res 2005;1045:124-
33. 
 
7.  Yang J, Yang Y, Chen JM, Liu WY, Wang CH, Lin BC. Central oxytocin enhances 
antinociception in the rat. Peptides 2007;28:1113-9. 
 
8.  Yang J. Intrathecal administration of oxytocin induces analgesia in low back pain 
involving the endogenous opiate peptide system. Spine 1994;19:867-71. 
 
9.  Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. 
Lancet 2006;367:1618-25. 
 10.  Eisenach JC, Pan PH, Smiley R, Lavand'homme P, Landau R, Houle TT. Severity of 
acute pain after childbirth, but not type of delivery, predicts persistent pain and 
postpartum depression. Pain 2008;140:87-94. 
 
 
 
 


Efficacy of Intrathecal Oxytocin  
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Protocol 
Efficacy of Intrathecal Oxytocin 
in Human Volunteers 
 
GOAL:  Determine the effect of intrathecal oxytocin on areas and intensity of hyperalgesia and 
allodynia induced by topical capsaicin. 
 
METHODS:  Equal numbers of healthy men and women will be recruited.  At least 3 days prior 
to study subjects will be trained to rate pain in response to heat applied to the lateral calf using a 
Peltier controlled thermode, and to rate pain in response to 225 mN von Frey filament testing 
within the area of hypersensitivity induced and maintained by transient application of topical 
capsaicin followed by intermittent heat (Petersen, 1999).   
Subjects will return for study visit two and be randomized into one of 3 groups of 12 
subjects each to receive, in a double-blind manner, intrathecal saline or intrathecal oxytocin, 15 
μg or 150 μg.  The solutions will be prepared and dispensed to this institution under IND 
approval and regulation from the Food and Drug Administration and will be released to the 
investigators through the research pharmacy at Wake Forest School of Medicine. 
A stimulus response to heat pain will be performed, then intrathecal injection of the study 
solution in a 3 ml volume will occur via a #27 or #25 Whitacre needle inserted in a lower lumbar 
interspace.  Thirty minutes later capsaicin will be applied to the lateral calf to generate 
hypersensitivity.  Capsaicin will be removed and the area re-kindled 40 min later by application 
of a thermode at 40ºC for 5 minutes.  Areas of hyperalgesia and allodynia and, within the area of 
hyperalgesia, stimulus response to von Frey filament testing, will be determined upon removal of 
capsaicin and after 3 rekindlings at 40 minute intervals.   
We will abandon an individual participant's study and schedule another participant to 
receive the same randomization, should we be unable to successfully place the intravenous 
catheter (IV) or the spinal needle to inject the intrathecal oxytocin. In our experience, this occurs 
in less than 10% of participants.  We maintain an extensive listing (IRB approved Database BG 
05-468: PI: James Eisenach, M.D.) of our previous Clinical Research Unit (CRU) volunteers 
who have requested to be notified by mail or email that they might qualify for participation in 
another volunteer study. It is from this list and potential volunteers that we maintain that we 


Efficacy of Intrathecal Oxytocin  
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anticipate recruitment of most of our volunteers. Should we need to advertise for additional 
volunteers we will submit a proposed advertising method to the IRB for approval.  
 
STUDY DESIGN 
Inclusion Criteria: We request permission to study up to 40 subjects so that we will have 36 
evaluable subjects. 
1. Male or female > 18 and < 60 years of age,  Body Mass Index (BMI) less than 40. 
2. Generally in good health as determined by the Principal Investigator based on prior 
medical history, American Society of Anesthesiologists physical status 1 or 2. 
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. 
Exclusion Criteria: 
 
1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, 
lidocaine or chili peppers. 
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 serum pregnancy test at screening visit), 
women who are currently nursing or lactating, or those who have delivered within 2 years. 
4. Currently taking prescription or over the counter pain medications (opioid or non-opioid), 
diuretics, blood pressure medication, heart medication or any other medication at the discretion 
of the investigators that would place the subject at increased risk.   
 


Efficacy of Intrathecal Oxytocin  
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RANDOMIZATION GROUPS 
A computer generated randomization will be used to determine the group for each subject. 
Subjects will be randomized to receive an intrathecal injection of the saline placebo or one of 
two doses oxytocin. 
 
 
 Study Visit 1:  The participant will report to the Clinical Research Unit (CRU) at least 3 
days prior to study visit 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 have blood drawn and sent to the laboratory 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 the forearm. Typically, the 
participant is exposed to temperatures between 380 and 510 C using a random staircase method.  
The participant will also be trained to reproducibly define the limits of hyperalgesia and 
allodynia on the skin of the lateral calf established by heating the skin to 45ºC for 5 minutes, 
applying topical capsaicin (0.075% cream, Bioglan Pharmaceuticals) under an occlusive dressing 
for 30 minutes, then heating the application site to 40ºC for 5 minutes every 40 minutes 
(rekindling) as previously described (Petersen, 1999).   
During this training period, the participant’s blood pressure, heart rate, and peripheral 
oxyhemoglobin saturation will be recorded.  A 12 Lead electrocardiogram (EKG) will also be 
performed. 
We have found this training session significantly reduces anxiety and variability in pain and 
hypersensitivity ratings on subsequent study days.  
 
 
Study Visit 2  
On the second visit, the participant will report to the CRU, in the morning after having had 
nothing to eat or drink since midnight. A peripheral intravenous catheter will be inserted into a 
vein in an upper extremity and lactated Ringers solution infused at 1.5 ml/kg/hr for the duration 
of the study. After obtaining baseline measures the subject will be placed into a lateral position 
and one of the investigator physicians will insert a #25 or #27 Whitacre spinal needle in a lumbar 
interspace using a sterile technique. After obtaining clear, free-flow CSF, a 2 milliliter sample of 
CSF will be obtained and stored for future use under IRB Protocol: 00003383, the sample will be 


Efficacy of Intrathecal Oxytocin  
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stored with a unique identifier.  Oxytocin in a 3 ml volume, diluted with sterile normal saline, or 
a 3 ml injection of sterile normal saline (placebo) will then be injected over 30 seconds. 
Oxytocin will be prepared by Med Solutions in Winston Salem, North Carolina and will be 
shipped to WFUHS for research study purposes only. The spinal needle will be removed and the 
volunteer placed supine with the head of the bed elevated for the next portion of the study.  30 
minutes after the spinal injection the skin on the lateral calf will be heated to 45ºC for 5 minutes 
then topical capsaicin cream will be applied to the lateral calf to generate hypersensitivity and 
remain on the skin for 30 minutes.  Capsaicin will be removed and the area re-kindled 40 min 
later by application of a thermode at 40ºC for 5 min.  Areas of hyperalgesia and allodynia and, 
within the area of hyperalgesia, stimulus response to von Frey filament testing, will be 
determined upon removal of capsaicin and after 3 re-kindlings at 40 minute intervals.  Three 
blood samples will be obtained after the spinal oxytocin injection at the following intervals: 10, 
45, 120 minutes. The blood will be drawn from the existing intravenous catheter that is in place. 
If the sample cannot be obtained through the intravenous catheter, the sample will be abandoned. 
The samples are being drawn for the analysis of systemic oxytocin after spinal administration.  
 
Safety and Monitoring: 
 
Assessment of Side Effects:  Significant side effects are defined as changes > 30% from baseline 
in the mean arterial pressure, HR, or oxyhemoglobin pulse oximetry < 90. Any unexpected or 
serious side effects will be reported to the IRB and the FDA within 24 hrs. Peripheral 
oxyhemoglobin saturation, BP and HR will be measured non-invasively before and 15, 30, 60, 
120, 180, 240, minutes after administering spinal oxytocin and the electrocardiogram will be 
monitored continuously for the duration of the study.   
 
A monitor tracing from the EKG will be recorded at 15 minute intervals for the first hour 
then hourly until discharge.  If either BP or HR change by > 30%, or oxyhemoglobin saturation 
decreases to less than 90, and require treatment, these vital signs will be repeated at 5-minute 
intervals until vital signs are stabilized. A screening neurologic exam along with questioning for 
qualitative symptoms will be performed at 45, 90, 150, 210, 240 minutes, and 24 hours. The 
screening neurologic test will consist of examining both an arm and leg for deep tendon reflexes 
(DTR's), light touch, extension/withdrawal strength. In addition we will ask the volunteer about 


Efficacy of Intrathecal Oxytocin  
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other symptoms to include sedation, anxiety, nausea, GI, bladder, dizziness, extremity weakness, 
or any other symptom which was not specifically asked. Any symptom proffered will be 
categorized on a scale of the volunteer's choosing.  
 
Treatment of Side Effects: Mean blood pressure elevations greater than 30% of baseline will be 
treated with labetalol 5-15 mg IV incrementally until BP elevation is less than 30% elevated. If 
BP elevation is judged to be due to pain following spinal oxytocin injection, we will treat pain 
first (at the volunteer's request) and only treat BP elevations if the volunteer has sufficient 
analgesia (he does not desire additional analgesia). Reductions in mean BP > 30% of baseline 
will be treated with incremental ephedrine 5-20 mg, IV. Heart rate (HR) reductions or elevations 
> 30% of baseline will be treated with incremental glycopyrolate 0.2 mg IV or propranolol 0.2 
mg IV, respectively. Peripheral oxyhemoglobin desaturation (< 90) will be treated with 
supplemental oxygen, nasal cannula, face mask, or non-rebreathing mask depending upon the 
degree desaturation and the response to therapy.  
 
Completion of Day 2 Assessment 
1. Vital signs are within normal limits blood pressure (systolic 90-140 mmHg; diastolic 
50-90 mmHg) resting heart rate 45-100 beats per minute) without medication 
2. He or she can ambulate without difficulty (no motor, balance affects). 
3. Someone other than the volunteer will take the volunteer home (requirement                      
 
 
for participation). 
4. Volunteer promises to stay home where he or she can be contacted by telephone 
(requirement for participation). 
We will instruct the volunteer to call us, providing beeper and telephone numbers of the 
research nurse and the investigators should he have any questions or problems. The research 
nurse will call the volunteer at 6 hours and 12 hours post-spinal oxytocin injection inquiring 
about any perceived problems.  
 
Study Visit 3: 
  Approximately 24 hours after the spinal oxytocin injection the subject 
will report to the CRU to have a blood sample drawn for a Basic Metabolic Panel to assess serum 
sodium levels. 


Efficacy of Intrathecal Oxytocin  
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RISKS 
 
Risks of spinal needle insertion include pain on insertion, local bruising or soreness, post-
dural puncture headache, and permanent nerve injury. Participants in this study will be informed 
regarding these risks.  Local anesthesia will be used to prevent pain on needle insertion, and a 
small (#25 or #27) Whitacre tip needle used to minimize local trauma and risk of headache.  We 
routinely telephone all volunteers daily for 5 days. Participants will also be contacted weekly for 
1 month, then approximately 6 months after the study to inquire regarding local discomfort or 
headache. There is a risk (less than 1%) of developing a headache from the spinal needles. If a 
subject develops a headache that does not go away and is bothersome, offer to perform an 
epidural blood patch. This procedure is 95% effective in treating the headache. Rarely (5 out of 
100 times) is a 2nd blood patch needed.  Other risks of the epidural blood patch are the same as 
the spinal. The risk of paralysis, infection or nerve damage from a spinal procedure is extremely 
rare, less than one chance in 20,000. The numbing medicine that we put under your skin right 
before the spinal needle is inserted may cause you to have a brief period (about 5 seconds) of 
mild discomfort. We have had no local discomfort lasting more than 2 weeks and only 1 
headache in 438 subjects that required epidural blood patch treatment. 
 
Risks of intrathecal oxytocin include unforeseen toxicity.  This drug will be studied under 
FDA oversight and approval.  The safety of spinal oxytocin has been extensively examined in 
animals, with no evidence of any nerve damage or other lasting effects, the FDA has approved 
this investigational study for humans, nearly 1000 humans have received spinal oxytocin in 
China without reported problems, and we did not observe toxicity in the recently completed 
Phase 1 study at this institution. Although this all suggests that it is safe to administer oxytocin, 
the exact risks are unknown. We will monitor subjects for many theoretical problems such as 
level of sleepiness, changes in blood pressure, heart rate and breathing. We will treat any side 
effects that the subject may experience if the changes are enough to concern us. 
 
 
HUMAN SUBJECTS 


Efficacy of Intrathecal Oxytocin  
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PI: James C. Eisenach, M.D. 
 
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All studies in volunteers will be performed in the CRU, which includes monitoring and 
resuscitation equipment and trained nursing support staff, or in in-patient settings of the Wake 
Forest Baptist Medical Center. All studies will be approved by the IRB and written informed 
consent obtained. The Project Investigators have all performed similar studies in volunteers and 
patients. The purpose of the study and all risks will be discussed with each volunteer, and all 
questions will be answered prior to obtaining written informed consent. Risks to be discussed 
include discomfort with needle and catheter insertion, risk of postdural puncture headache and 
spinal needle insertion, and potential period of pain if the study drugs are ineffective. The most 
likely bothersome risk to volunteers will be that of headache from i.t. needle insertion. We will 
discuss options for headache treatment including oral caffeine and epidural blood patch at the 
time of original consent and again should a headache occur. These will be provided at no charge 
to the volunteer, paid for by departmental funds. All data acquired will remain confidential with 
no reference to individuals in publications.   
Data Safety Monitoring Plan 
 
 This Phase II trial will be performed with a data safety monitoring committee (Laura 
Dean, MD and Francis Walker, M.D.) who is not involved in the study.  Data and adverse events 
will be reported to these individuals quarterly. Adverse events will also be reported to the IRB 
and the FDA (since trials are being conducted under an IND).  Serious adverse events will be 
reported to all of these groups and the data safety monitoring individuals within 24 hr and the 
trials halted until feedback is obtained from each. Data and any adverse events will be monitored 
and reviewed by the PI after treatment of each subject.  
Minority, Gender, and Children Participation 
Based on previous experience with volunteer studies, women will represent 40-60% of 
participants in the proposed studies. However, as seen in the table below from the past cycle with 
volunteers, it is unlikely that more than 20% of participants will be minorities. There is no reason 
to suspect a difference among races in response to these analgesic compounds, so from a 
scientific viewpoint this will not be detrimental. We will recruit form our IRB approved 
Database (BG 05-468).  Children under age 18 are not included in these protocols because this 
protocol involves the use of experimental compounds and we believe they should be first 
characterized in adults. Furthermore, the study of experimental pain in children volunteers is 


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difficult ethically. For these reasons we anticipate studying approximately 6-7% of our subjects 
under age 21, and none under age 18.   
 
Volunteer Payment 
Participants will be paid a total of $500.  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.  
Placement of IV: $25 
If IV placement unsuccessful, the volunteer is paid and the study abandoned. 
Placement of Spinal: $125 and study drug administration 
If the 1st spinal is attempted but proves unsuccessful, the volunteer is paid $100 
and the study abandoned,  
Application of capsaicin cream: $25 for each application (total $50) 
Completion of entire study: $300 
Volunteer must complete all of the above phases to receive this payment. 
 
Long-term Follow-up 
Volunteers will be contacted daily for 5 days, weekly for 1 month, and at 6 months after 
the study and questioned about neurologic symptoms, symptoms of post-dural puncture headache 
(spinal headache) or other complaints. 
 
STATISTICAL RATIONALE 
Primary outcome measure will be the area of hyperalgesia after the first skin heating following 
topical capsaicin. 
Group comparison:  Areas of hyperalgesia after the first skin heating following topical 
capsaicin will be compared among the three groups using one-way ANOVA. 
Power analysis: Based on previously published work by us with this model in which the 
intrathecal placebo group had an area of hyperalgesia of 62 ± 12 cm2, a group size of 12 will 
allow us to observe a difference among groups of 15 cm2 with α=0.05 and 1-β=0.80.  A 25% 
reduction in area of hyperalgesia is considered by us and other groups to be clinically predictive 


Efficacy of Intrathecal Oxytocin  
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of reduction in hyperalgesia and in spontaneous pain in patients with neuropathic pain with the 
same intervention. 
 

ICF_000.pdf: 
NCT01996605
Official Title: Efficacy of Intrathecal Oxytocin in Human Volunteers 
IRB-Approved Date:  1/25/22


Page 1 of 12
Adult Consent Form
Version: 1/25/2022
Department/Section of Anesthesiology
EFFICACY OF SPINAL OXYTOCIN IN HUMAN SUBJECTS
Informed Consent Form to Participate in Research
James C. Eisenach, M.D., Principal Investigator
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 subject. 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?
This research study is being done because pain is a significant problem for patients with a variety 
of medical problems and following surgery or traumatic injury. Currently available pain 
medications may not treat all types of pain or may treat pain only at doses that produce side 
effects and complications. The medication in this study may have a role in better treatment of 
pain. Oxytocin is commonly given by IV (into a vein) to treat certain types of pain. This is the 
second study in the United States to examine the effects of oxytocin given into the spinal fluid in 
the back. We believe that spinal oxytocin may prove to be an excellent pain killer for certain 
types of pain which sometimes occur with cancer or follow nerve injury after accidents or 
surgery. At present, there are not good treatments for this type of pain and your participation in 
this study may help researchers better understand this type of pain and perhaps develop new 
ways of treating this pain.
The goals of this study are to see if a dose of oxytocin, given into the fluid in your back near the 
spine has any effect on pain or discomfort in the skin sensation that will take place after applying 
capsaicin (chili pepper) cream.  The sunburn-like sensation that people experience after having 
capsaicin cream applied is similar to, but much milder than, the pain that some people have after 
surgery and after certain types of nerve injuries.  
Oxytocin has been approved by the US Food and Drug Administration (FDA), but the 
preparation and route of administration being used in this study has not been approved. However, 
the study is being conducted under the review of the FDA. At this time, there is not a form of 
Oxytocin that is available on the open market for spinal administration.
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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 diseases or medical conditions. In this study you will 
either receive the active study medication, oxytocin or placebo which is not active. 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 study 36 people at people at this research site. In order to identify the 36 subjects needed, 
we may need to screen as many as 40 people because some people will not qualify to be included 
in the study.
WHAT IS INVOLVED IN THE STUDY?
You will have three visits (detailed below) to the Clinical Research Unit (CRU).  If you take 
part in this study, all of the test and procedures performed will be solely for research purposes.
You will be randomized into one of the study groups described below. Randomization means 
that you are put into a group by chance. It is like flipping a coin. You will have a one in three 
chance of being placed in any group.
Group 1- will receive 15 micrograms of spinal oxytocin
Group 2- will receive 150 micrograms of spinal oxytocin 
Group 3- will receive saline (placebo) in the spinal injection 
Neither you nor the investigator will know which group you are in. 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.
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).  
Electrocardiogram (EKG): tracing of the rhythm of your heart.
Laboratory Testing: female participants of child-bearing potential will have blood drawn to 
determine that they are not pregnant. 
Thermal Heat Testing: we will train you to accurately describe pain from a small heat 
probe (1.5 inches). The tip of the heat probe that will be applied to you’re the skin on your 
forearm is about the size of a penny.  The thermal heat probe will be controlled by a computer 
that is programmed to deliver temperatures that range from skin temperature up to a temperature 
that is hot (124 ºF) and uncomfortable, but does not burn your skin. We will ask you to rate the 
pain by using a sliding scale. Most volunteers find that they can learn to tell very small 
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differences in the temperature probe accurately.  
Light Touch Testing: a von Frey filament (a plastic thread like a paint brush bristle) and a 
cotton wisp (Q-tip) will be lightly applied to your skin. We will ask you to tell us when you feel 
a difference in the sensitivity on your skin. We will use a washable marker to “mark” the areas 
that you tell us are more sensitive.
Capsaicin Testing: we will place the thermal heat 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 test your skin 
sensations with the filament and cotton wisp, after which capsaicin cream (an over-the-counter 
pain relief cream) will be put on your skin in the same spot as the heat probe. The cream will be 
on your skin for 30 minutes. During this time we will ask you to rate any pain you feel every 5 
minutes. We will remove the capsaicin cream from your skin with a soft cloth. After removing 
the cream, we will then test your skin sensations with the filament and Q-tip as described in the 
Light Tough Testing.
‘Rekindling’ of the Capsaicin Testing Area: 40 minutes after removing the capsaicin cream, 
we will apply thermal heat at a temperature of 104F to the same area where the capsaicin cream 
was applied to. We will leave the heat on your skin for five minutes. At the end of the five 
minutes we will ask you to rate any pain you are experiencing. This procedure is known as 
“rekindling”. We will test your skin sensations with the filament and cotton wisp (Light Touch 
Testing) before and after this second heating.
Blood Draw: we will draw 3 blood samples from the IV that we have placed in your arm; the 
total amount for each sample will be 1 teaspoon. We will draw a total of 3 teaspoons. If we 
cannot draw the blood from your IV we will perform an additional venipuncture. 
Study Visit 1:
During the first study visit we will record your 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. We will 
perform an electrocardiogram (EKG), to obtain a baseline tracing of your heart and female 
participants of child-bearing potential will have approximately 1 teaspoon of blood drawn for a 
pregnancy test. We will also train you to rate pain in response to heat applied to your forearm 
and the outside of your lower leg (Thermal heat testing and Capsaicin testing). We will then 
perform one cycle of the capsaicin testing, providing you the opportunity to experience the 
testing and to be trained in evaluating the area of sensitivity. This visit will last approximately 2 
hours.
Study Visit 2:
On the morning of the second session you will come to the Clinical Research Center (CRU) 
having had nothing to eat or drink after midnight.  We will record your blood pressure, heart rate, 
the amount of oxygen in your blood, and we will connect you to a heart monitor. We will again 
perform a short training session with the heat probe. Then we will insert an intravenous catheter 
into a vein in your arm and you will get IV fluid through this catheter. 
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We will then ask you to curl up into a ball on your side on a bed and put a spinal needle into the 
spinal space in the lowest part of your back after numbing the skin with lidocaine. After 
successfully placing the spinal needle, we will take a sample approximately one-half of a 
teaspoon of your spinal fluid and then we will then inject the oxytocin or placebo according to 
the randomization that has been selected for you. The spinal needle will then be withdrawn and 
you will be asked to lie on your back with the head of the bed elevated slightly.
Thirty minutes after the spinal injection we will perform the testing with the capsaicin cream. We 
will perform 3 cycles of testing on the area where the capsaicin was applied at 40 minute 
intervals. 
Multiple times during this day (from just before the spinal until 3.5 hours after the spinal 
injection) we will measure your blood pressure, measure the oxygen in your bloodstream with 
the finger-clip, examine you to test your arm and leg strength, and sensations, (to test for any 
changes in the strength or sensation you have in your arms and legs) and ask you to about any 
other sensations you may be experiencing.  We will also monitor your electrocardiogram 
throughout the study period.  
About 3.5 hours after the spinal injection we will stop gathering information for the study. To go 
home, you must not have any side effects that would prevent you from walking (like dizziness, 
unsteadiness). You must have someone drive you home and you must be available for us to call 
you at home. We will call you 6 hours after the spinal drug injection and 12 hours after the spinal 
drug injection. You must call us if you have any questions or concerns during this period. There 
is a remote chance that should you experience side effects which are concerning, we will keep 
you in the hospital overnight.
Study Visit 3:
You must return to the CRU approximately 24 hours after the spinal drug injection.  You will 
have approximately 1 teaspoon of blood withdrawn from a vein during the 24 hour follow up 
visit to have your electrolytes evaluated.  After all of the measurements are finished, the study 
will be complete. We will call you daily for 5 days, then weekly for 1 month, then approximately 
6 months after the study and ask you about any symptoms that you believe you might have 
experienced. If at any time you have a question or a concern, please call us.
Storage of Biological Tissue
If you agree to participate in this study, we will draw one-half of a teaspoon (2 milliliters) of cerebrospinal 
fluid (CSF) prior to injection of the study medication to use for future research. This sample will be kept 
and may be used in future research to learn more about other diseases.  Your sample will be obtained in the 
Clinical Research Unit by the Anesthesiology Department at Wake Forest University Baptist Medical 
Center. The sample will be stored in the Pain Mechanisms Laboratory and it will be given only to 
researchers approved by Dr. James Eisenach.  An Institutional Review Board (IRB) must also approve any 
future research study using your tissue sample. In order to participate in this study, you must be willing to 
provide this sample for future research.
Your CSF sample will be stored with a unique identifier and will not include any identifiable 
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information about you such as your name, address, telephone number, social security number, 
medical record number or any of the identifiers outlined in the HIPAA Privacy Rule. The unique 
identifier will be a randomly assigned number and only the principal investigator will have 
access to the code that links the unique identifier to you. Your name, address, social security 
number, etc., will never be disclosed to future researchers and neither will the code that links 
your identifiers to the sample.
The research that may be performed with your CSF sample is not designed to help you 
specifically. There is no personal benefit to you from taking part in this aspect of the research 
study. It might help people who have diseases at some point in the future, but it is not known if 
this will happen. The results of the research performed with your CSF will not be given to you or 
your doctor. The results will not be put in your medical record. The research using your CSF 
sample will not affect your care.
Your CSF sample will be used only for research and will not be sold. The findings from this 
research may result in the future development of products that are of commercial value. There 
are no plans to share any of the profits with you which may occur as a result of the research.
HOW LONG WILL I BE IN THE STUDY?
You will attend 3 study visits. Following visit 2, we will contact you by telephone 6 and 12 hours 
following the spinal drug injection. Following visit 3, we will contact you by telephone daily for 
5 days, then weekly for 1 month, then approximately 6 months later. Total study duration is 
approximately 6 months.
You can stop participating at any time. 
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. The risks are given below. You should discuss the 
risk of being in this study with the study staff. 
Heat Probe 
You may experience brief pain during the thermal heat testing. 
Capsaicin
Risks of the capsaicin include: pain and allergic reaction.  
Oxytocin
The safety of spinal oxytocin has been extensively examined in animals, with no evidence of any 
nerve damage or other lasting effects, the FDA has approved this investigational study for 
humans, and nearly 1000 humans have received spinal oxytocin in China without reported 
problems. Although this all suggests that it is safe to administer oxytocin, the exact risks are 
unknown. We will monitor you for many theoretical problems such as your level of sleepiness, 
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.
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Institutional Review Board 
IRB Number:IRB00025901
Meeting Date Approved 1/25/2022          
Version Valid Until: 1/24/2023


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Spinal Procedures
Risks associated with the spinal procedures are mild bruising and soreness in the area.  There is a 
risk (less than 1%) of developing a headache from the spinal needles. If you develop a headache 
that does not go away and is bothersome, we will talk to you about an epidural blood patch. This 
is a simple procedure, which would involve putting a needle in the epidural space in your back 
and injecting some blood taken from your arm. This procedure is 95% (95 times out of 100) 
effective in treating the headache.  However you would have a 1 in 3 chance of having a 
backache for a few days. Rarely (5 out of 100 times) is a 2nd blood patch needed.  Other risks of 
the epidural blood patch are the same as the spinal. You will not be charged if you need an 
epidural blood patch to treat a headache. The risk of paralysis, infection or nerve damage from a 
spinal procedure is extremely rare, less than one chance in 20,000. The numbing medicine that 
we put under your skin right before the spinal needle is inserted may cause you to have a brief 
period (about 5 seconds) of mild discomfort.
We may be unable to place the spinal needles due to the shape of your back. If we cannot place 
the spinal needles, you would no longer be able to continue participating in the study.  You will 
be paid as detailed below. 
Risks from Needle Insertions
You may experience discomfort, bruising and/or bleeding where the needle is inserted. 
Occasionally some people become dizzy lightheaded or feel faint. Infection may occur on rare 
occasions.  
For Electrocardiogram (ECG):
The electrode pads used during the ECG may cause minor skin redness or irritation.
You can call the study staff at any time if you think you might be having any of the side effects 
discussed above. Also, the study staff will be telephoning you each day for 5 days after the study, 
then weekly for 1 month, then approximately 6 months after the study and ask you about any 
symptoms that you believe you might have experienced. If at any time you have a question or a 
concern, please call us.
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.
A Data Safety and Monitoring Committee, an independent group of experts, will be reviewing 
the data from this research throughout the study.
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Institutional Review Board 
IRB Number:IRB00025901
Meeting Date Approved 1/25/2022          
Version Valid Until: 1/24/2023


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Reproductive Risks and other Issues to Participating in Research
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 ABOUT MY HEALTH INFORMATION?
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), 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.
1) Monitors, auditors, IRB or other regulatory agencies will be granted direct access to the 
participant’s original medical record for verification of clinical trial procedures or data, 
without violating confidentiality of the participant and to the extent permitted by other 
applicable laws.
2) Representatives from government agencies such as the US Food and Drug 
Administration (FDA), the Department of Health and Human Services (DHHS).
 
3)   Representatives from government agencies such as the Office for Human Research 
Protections and other similar agencies.
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If required by law or court order, we might also have to share your Protected Health Information 
with a judge, law enforcement officer, government agencies, or others. If your Protected Health 
Information is shared with any of these groups it may no longer be protected by federal or state 
privacy rules.
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 and any research information entered into your medical record will be kept for as long as 
your medical record is kept by the Medical Center. 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. 
Laboratory test results and other medical reports created as a result of your participation in the 
research study may be entered into the computer systems of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital.  These will be kept secure, with access to this 
information limited to individuals with proper authority, but who may not be directly involved 
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with this research study.
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 THE COSTS?
There are no costs to you for taking part in this study. 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 YOU BE PAID FOR PARTICIPATING?
You will be paid $500(outlined below) if you complete all the scheduled study visits. If you 
withdraw for any reason from the study before completion you will be paid for the portion of the 
study that you completed.  

Placement of IV: $25

Placement of Spinal: $125 and study drug administration (if spinal  placement is 
unsuccessful, the study will be abandoned and the subject paid for the portion completed)

Application of capsaicin cream: $25 for each application (total $50)

Completion of entire study (completing 3 study visits with all data collection): $300
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 National Institutes of Health. 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. 
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health. The researchers with this Certificate may not disclose or use information, documents, or 
biospecimens that may identify you in any federal, state, or local civil, criminal, administrative, 
legislative, or other action, suit, or proceeding, or be used as evidence, for example, if there is a 
court subpoena, unless you have consented for this use. Information, documents, or 
biospecimens protected by this Certificate cannot be disclosed to anyone else who is not 
connected with the research except, if there is a federal, state, or local law that requires 
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disclosure (such as to report child abuse or communicable diseases but not for federal, state, or 
local civil, criminal, administrative, legislative, or other proceedings, see below); if you have 
consented to the disclosure, including for your medical treatment; or if it is used for other 
scientific research, as allowed by federal regulations protecting research subjects.
The Certificate cannot be used to refuse a request for information from personnel of the United 
States federal or state government agency sponsoring the project that is needed for auditing or 
program evaluation by The National Institute of Health which is funding this project or for 
information that must be disclosed in order to meet the requirements of the federal Food and 
Drug Administration (FDA).  You should understand that a Certificate of Confidentiality does 
not prevent you from voluntarily releasing information about yourself or your involvement in 
this research. If you want your research information released to an insurer, medical care 
provider, or any other person not connected with the research, you must provide consent to allow 
the researchers to release it
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 Dr. James Eisenach at 
 or after 
hours you should call the study coordinator by calling 
. 
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 
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at any time. This could be because you failed to follow instructions or because the entire study 
has been stopped.
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 and 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 page 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
.
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 
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Institutional Review Board 
IRB Number:IRB00025901
Meeting Date Approved 1/25/2022          
Version Valid Until: 1/24/2023


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Person Obtaining Consent: ___________________________ Date: ________ Time: ________ am pm 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00025901
Meeting Date Approved 1/25/2022          
Version Valid Until: 1/24/2023