Clinical trial NCT02100956
Conditions: Neuropathic Pain
Keywords: chronic pain neuropathic pain
Sponsor: Wake Forest University Health Sciences
Start date: 2014-06-19; Completion date: 2022-10-10
Enrollment: 8 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of the study is to determine the effect of oxytocin given into the spinal fluid on pain and areas and intensity of hyperalgesia and allodynia in patients with chronic neuropathic pain.

Detailed description:
Rationale: The investigators anticipate that oxytocin will be effective after spinal injection in humans to acutely relieve chronic neuropathic pain.

Objectives: Determine the effect of intrathecal oxytocin on pain and areas and intensity of hyperalgesia and allodynia in patients with chronic neuropathic pain.

Interventions: A computer generated randomization will be used to determine the group for each subject. Subjects will be randomized to receive an intrathecal injection of saline (placebo) or oxytocin.

Arms: arm 1: The subject first received oxytocin 100 micrograms administered intrathecally (IT). After at least one week, they received normal saline placebo IT. arm 2: The subject first received normal saline placebo intrathecally (IT). After at least one week, they then received oxytocin 100 micrograms administered IT.
Interventions: intervention 1: oxytocin 100 micrograms intervention 2: Normal Saline (preservative free)
Intervention descriptions: intervention 1: oxytocin 100 micrograms administered intrathecally (IT) intervention 2: Normal Saline (preservative free) administered intrathecally (IT)

Protocol documents:
Prot_SAP_001.pdf: 
Efficacy of Intrathecal Oxytocin  
in Patients with Neuropathic Pain 
 
 
 
PI: James C. Eisenach, M.D. 
 
1 
8/18/2021 
 
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  
in Patients with Neuropathic Pain 
 
 
 
PI: James C. Eisenach, M.D. 
 
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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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PI: James C. Eisenach, M.D. 
 
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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 to acutely 
relieve chronic neuropathic pain.  For these future studies, we will use a cross over, controlled 
and blinded study of intrathecal oxytocin in patients with neuropathic pain below the umbilicus, 
with primary outcome being visual analog score for pain and secondary outcomes being areas of 
increased pain sensation to a normally painful stimulus (hyperalgesia) and pain sensation to what 
previously was an innocuous stimulus (allodynia).     
 


Efficacy of Intrathecal Oxytocin  
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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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PI: James C. Eisenach, M.D. 
 
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Protocol 
Efficacy of Intrathecal Oxytocin 
in Patients with Neuropathic Pain 
 
GOAL:  Determine the effect of intrathecal oxytocin on pain and areas and intensity of 
hyperalgesia and allodynia in patients with chronic neuropathic pain. 
 
METHODS:  Equal numbers of healthy men and women will be recruited.  On a day at least 3 
days before study, patients will come to the CTSI Clinical Research Unit (CRU) to review the 
informed consent, confirm eligibility criteria, and be trained to rate pain in response to heat 
applied to an area of normal skin without ongoing pain using a Peltier controlled thermode, and 
to rate pain in response to 225 mN von Frey filament testing within the area of hyperalgesia, if 
present.   
Subjects will come to the CTSI CRU at least 3 days later and be randomized into one of 2 
groups of 20 subjects each to receive, in a double-blind manner, intrathecal saline or intrathecal 
oxytocin, 100 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.  Following 
subject rating of their ongoing pain and mapping of areas of allodynia and hyperalgesia, as well 
as rating of pain by a 225 mN von Frey filament applied in the area of hyperalgesia, an 
intrathecal injection of the study solution in a 3 ml volume will be performed via a #27 or #25 
Whitacre needle inserted in a lower lumbar interspace.  Subjects will rate their ongoing pain and 
that from the von Frey filament in the area of hyperalgesia, and we will map the areas of 
hyperalgesia and allodynia at 30, 60, 90, 120, 180, and 240 min after injection.  Subjects will 
return a second time to the CTSI CRU at least 1 week after the first study session and the same 
procedures will be performed, except that they will receive the other intrathecal study drug 
solution (e.g., if they received saline on study session 1, they will receive oxytocin on study 
session 2). 
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 spinal needle to 
inject study solution. In our experience, this occurs in less than 10% of participants.  Subjects 
will be recruited at Wake Forest School of Medicine pain clinics, and Orthopaedic and Podiatry 


Efficacy of Intrathecal Oxytocin  
in Patients with Neuropathic Pain 
 
 
 
PI: James C. Eisenach, M.D. 
 
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clinics at the Wake Forest Davie County facility. Subjects will also be recruited from our 
existing database BG 05-468 and we will also utilize the Clinical Translational Science 
Institute’s (CTSI) Enterprise Data Warehouse (EDW) and approved advertising in the 
community for potential subjects. 
 
STUDY DESIGN 
Inclusion Criteria: We request permission to study up to 44 subjects so that we will have 40 
evaluable subjects. 
1. Male or female > 18 and < 70 years of age, with a BMI <40. 
2. Presence of neuropathic pain for > 6 months, with primary pain area below the umbilicus.  
We will focus recruitment efforts on low back pain with a neuropathic component to the lower 
extremities, but will accept other causes of neuropathic pain. 
3. 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. 
4. Blood pressure (systolic 90-150 mmHg; diastolic 50-90 mmHg) resting heart rate 45-100 
beats per minute. 
5. All subjects must be vaccinated against SARS-CoV-2, with proof via vaccination card or 
the NC HHS form. 
 
Exclusion Criteria: 
 
1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug,  
lidocaine, or latex. 
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 and 
adenomyosis as reported on history), compromise the subject’s compliance with study procedures, 
or compromise the quality of the data. 


Efficacy of Intrathecal Oxytocin  
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PI: James C. Eisenach, M.D. 
 
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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.  Pain treatment that includes spinal cord stimulators, chronic intrathecal drug therapy, or 
oral opioid treatment for > 3 months at a current dose of > 100 mg morphine per day or 
equivalent. 
 
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 100 μg 
oxytocin on the first study visit, with the other on the second. 
 
 
 Study Visit 1:  The participant will report to the CTSI 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.  Participants will be trained to estimate pain quantitatively using a 2 cm2 peltier 
controlled thermode (TSA®) applied to an area of normal skin outside the area of ongoing pain. 
Typically, the participant is exposed to temperatures between 380 and 510 C using a random 
staircase method.   
During this training period, the participant’s blood pressure, heart rate, and peripheral 
oxyhemoglobin saturation will be recorded.  A 12 Lead electrocardiogram (ECG) will also be 
performed.  
 
 
Study Visit 2  
On the second visit, the participant will report to the CTSI CRU in the morning. 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 stored with a unique identifier.  


Efficacy of Intrathecal Oxytocin  
in Patients with Neuropathic Pain 
 
 
 
PI: James C. Eisenach, M.D. 
 
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Oxytocin, 100 μg  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 Compounding, Winston-Salem, NC 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.  Ongoing pain, pain to 225 mN von Frey filament application in 
the area of hyperalgesia, and areas of hyperalgesia and allodynia will be determined at 30, 60, 
90, 120, 180, and 240 min after spinal injection.  Blood samples (5 ml) will be obtained at 10, 
20, 40, and 75 min after spinal injection by aspiration from the indwelling catheter, plasma will 
be prepared from the samples and frozen for subsequent analysis for oxytocin content.  If blood 
cannot be obtained from the catheter we will not collect samples. 
 
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 ECG 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, and 240 minutes. 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 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.  
 


Efficacy of Intrathecal Oxytocin  
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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 20% of those on admission to the CRU 
2. He or she can ambulate without difficulty (no motor, balance affects). 
3. Someone other than the subject will take the subject home (requirement                       
 
for participation). 
4. Subject promises to stay home where he or she can be contacted by telephone 
(requirement for participation). 
We will instruct the subject 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 subject at 6 hours and 12 hours post-spinal study drug injection inquiring 
about any perceived problems.  
 
Study Visit 3: 
  Approximately 24 hours after the spinal oxytocin injection the subject 
will report to the CTSI CRU to have a blood sample drawn for a Basic Metabolic Panel to assess 
serum sodium levels. 
 
Study Visit 4: 
At least one week after Study Visit 2 the subject will return to the CTSI 
CRU for intrathecal injection of the cross over study solution.  All procedures will be the same as 
Study Visit 2. 
 


Efficacy of Intrathecal Oxytocin  
in Patients with Neuropathic Pain 
 
 
 
PI: James C. Eisenach, M.D. 
 
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Study Visit 5: 
  Approximately 24 hours after the spinal oxytocin injection the subject 
will report to the CTSI CRU to have a blood sample drawn for a Basic Metabolic Panel to assess 
serum sodium levels. 
 
 
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 subjects 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 and in a study of over 90 subjects undergoing hip replacement surgery 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. 


Efficacy of Intrathecal Oxytocin  
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PI: James C. Eisenach, M.D. 
 
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HUMAN SUBJECTS 
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.   
 
Previous Experience in the CRU 
These investigators have, under NIH grant GM48085, regularly performed intrathecal injection 
studies with novel drugs for intrathecal delivery in healthy volunteers and in patients since 1990.  
Drugs studied include clonidine, fentanyl, neostigmine, adenosine, ketorolac and oxytocin.  In 
addition, we have studied drugs approved for intrathecal delivery (morphine and bupivacaine) in 
the CRU.  The most common adverse effect from these studies has been mild, transient backache 
and headache.  Persistent headache requiring blood patch has occurred in <1% of subjects, likely 
reflecting the use of very small gauge (#27), pencil point spinal needles.  Drug related adverse 
effects have included hypotension and bradycardia (clonidine), nausea (fentanyl, neostigmine), 
mild respiratory depression (fentanyl), transient back and leg pain (adenosine) and one episode 
of hypotension and bradycardia consistent with a vaso-vagal response to injection (oxytocin).  
The IRB and FDA recognizes that there are potential risks to these studies and has supported 
performance of this research in the CRU with the presence of an anesthesiologist and nurse, 


Efficacy of Intrathecal Oxytocin  
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appropriate monitoring, intravenous access, and immediate access to appropriate drugs for 
treatment. 
 
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. 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 
difficult ethically. For these reasons we anticipate studying approximately 6-7% of our subjects 
under age 21, and none under age 18.   
 
Subject Payment 
Participants will be paid a total of $800 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.  
Placement of IV on each study day: $25 
If IV placement unsuccessful, the volunteer is paid and the study abandoned. 
Placement of Spinal on each study day: $100 and study drug administration 
If the 1st spinal is attempted but proves unsuccessful, the volunteer is paid $100 
and the study abandoned.  
• Completion of study Visit 2 (first spinal injection): $150 


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• Completion of study Visit 4: (second spinal injection): $250 
• Completion of entire study (completion of all study related procedures): 
$150 
Volunteer must complete all of the above phases to receive the total payment. 
 
 
 
Long-term Follow-up 
Subjects 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. We will also collect a verbal pain score during these 
follow ups. 
 
STATISTICAL RATIONALE 
Primary outcome measure will be ongoing pain by visual analog scale. 
Group comparison:  Pain will be compared using a repeated measures ANCOVA. 
Power analysis: Based on previously published work by us with this model in which the patient 
population has an ongoing pain level of 4.3 ± 2.0 and a reduction in pain 60 min after injection 
of 0.9 ± 1.5, a group size of 40 will allow us to observe a difference between placebo and 
treatment of 0.7 with α=0.05 and 1-β=0.80.   
 

ICF_000.pdf: 
NCT02100956
Official Title: Efficacy of Intrathecal Oxytocin in Patients With Neuropathic Pain
IRB-Approved Date:  6/20/22


Page 1 of 13
Adult Consent Form
Version:   8/18/2021
Department/Section of Anesthesiology
EFFICACY OF INTRATHECAL OXYTOCIN IN PATIENTS WITH 
NEUROPATHIC PAIN
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 have chronic nerve pain (burning or stinging type pain in the lower part of 
your body). 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 neuropathy or nerve pain is a significant problem for 
patients 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 third 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 your current nerve pain. 
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. At this 
time, there is not a form of Oxytocin that is available on the open market for spinal 
administration.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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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 enroll 40 people at Wake Forest Baptist Health to take part in this study. In order to 
identify the 40 subjects needed, we may need to screen as many as 44 because some people will 
not qualify to be included in the study.
To be considered for inclusion in this study, you must have been vaccinated against SARS-CoV-
2 (COVID-19). We will request to see a copy of your verification record (vaccine card or North 
Carolina Health and Human Services printed form).
WHAT IS INVOLVED IN THE STUDY?
You will have five 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 an equal chance 
of being placed in one of the two study groups.
Group 1- will receive 100 micrograms of spinal oxytocin in your first spinal injection and 
placebo (saline) in your second spinal injection
Group 2- will receive placebo (saline) in your first spinal injection and 100 micrograms of spinal 
oxytocin in your second 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 (ECG): 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. Blood will be sampled 4 times after the spinal injection 
from the existing intravenous catheter.
Thermal Heat Testing: we will train you to accurately describe pain from a small heat 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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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 
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.
Study Visit 1:
During the first study visit we will explain all study related procedures, 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 (ECG), 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 an arm/leg that you are currently experiencing no pain (Thermal heat testing). We will use the 
von Frey filament (a plastic thread like a paint brush bristle) and a cotton wisp (Q-tip) to test 
your area of sensitivity in your area of nerve pain (Light touch testing). 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 use the 
von Frey filament (a plastic thread like a paint brush bristle) and a cotton wisp (Q-tip) to test 
your area of sensitivity in your area of nerve pain (Light touch testing) and ask you to rate your 
pain using a plastic sliding scale. Then we will insert an intravenous catheter (IV) into a vein in 
your arm and you will get IV fluid through this catheter. We will also take 4 blood samples from 
this IV after your spinal injection of the study medication to check the level of oxytocin in your 
blood. If we cannot draw the blood from the IV catheter we will not perform a separate needle 
stick. You will have approximately 1 teaspoon of blood withdrawn from a vein 4 times 
throughout study visit 2. 
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 inject the oxytocin or placebo according to the 
group that you were randomly assigned. 
The spinal needle will then be withdrawn and you will be asked to lie on your back with the head 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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of the bed elevated slightly.
Multiple times during this day (from just before the spinal until 4 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 4 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. This visit will last approximately 6 hours.
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.  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 and we will ask you to give us a verbal pain score. If at any 
time you have a question or a concern, please call us.
Study Visit 4:
At least one week after study visit 2 we will schedule you an appointment to return to the CRU 
for your fourth visit.  On the morning of the fourth 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 use the von Frey filament (a plastic thread like a paint brush bristle) and a 
cotton wisp (Q-tip) to test your area of sensitivity in your area of nerve pain (Light touch testing) 
and ask you to rate your pain using a plastic sliding scale. Then we will insert an intravenous 
catheter into a vein in your arm and you will get IV fluid through this catheter. We will also take 
4 blood samples from this IV after your spinal injection of the study medication to check the 
level of oxytocin in your blood. If we cannot draw the blood from the IV catheter we will not 
perform a separate needle stick. You will have approximately 1 teaspoon of blood withdrawn 
from a vein 4 times throughout study visit 4.  The total amount of blood withdrawn during the 
entire study will be approximately 2 ounces.
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 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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the randomization that has been selected for you (this time you will receive opposite of what you 
received in your spinal injection on study visit 2). 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.
Multiple times during this day (from just before the spinal until 4 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 4 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. This visit will last approximately 6 hours.
Study Visit 5:
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.  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. We will also collect a verbal pain score during these follow 
ups. 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 
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.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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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 be in the study for about 1-3 weeks. However we will contact you by telephone 6 hours 
and 12 hours after you leave the research clinic. We will also contact you daily for 5 days, 
weekly for a month and then at 6 months following your study.
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. 
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.
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 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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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.
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. Reliable methods 
of birth control are: abstinence (not having sex), oral contraceptives, intrauterine device (IUD), 
DepoProvera, tubal ligation, or vasectomy of the partner (with confirmed negative sperm counts) 
in a monogamous relationship (same partner). An acceptable, although less reliable, method 
involves the careful use of condoms and spermicidal foam or gel and/or a cervical cap or sponge. 
We encourage you to discuss this issue further with your physicians if you have any questions.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
You may or may not benefit from participating in this 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?
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.
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. Only the following people or organizations will be granted access to your 
Protected Health Information:
1) The study investigator and his/her staff, or others at Wake Forest University Health 
Sciences who oversee research
2) Other people or laboratories providing services for this research project on behalf of 
Wake Forest University Health Sciences and Wake Forest University Baptist Medical 
Center 
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 
law.
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.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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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 
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 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. 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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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.
The purpose of this research study is to obtain data or information on the safety and/or 
effectiveness of Oxytocin administered spinally; the results will be provided to the sponsor, the 
Food and Drug Administration and other federal and regulatory agencies as required.
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 
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 National Institutes 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.
WILL YOU BE PAID FOR PARTICIPATING?
You will be paid $800 (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 each (total of $50)

Placement of Spinal: $100 (total $200) and study drug administration (if spinal  
placement is unsuccessful, the study will be abandoned and the subject paid for the 
portion completed) 

Completion of study visit 2 (first spinal injection): $150

Completion of study visit 4 (second spinal injection): $250

Completion of entire study: $150

To receive the entire $800 you must complete all study related visits and procedures.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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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.
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 
.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


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WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
at any time. This could be because 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.
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 
.
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:___________________________ Date:_________ Time:________ am pm
    
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023


Page 13 of 13
Adult Consent Form
Version:   8/18/2021
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00027272
Meeting Date Approved 6/20/2022          
Version Valid Until: 6/19/2023