Conditions: Healthy Volunteer Study
Keywords: Acute Pain Chronic Pain Intravenous Oxytocin Intranasal Oxytocin
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 25
Healthy volunteers: yes

Brief summary:
The main purpose of this study is to sample blood and model the plasma pharmacokinetics (PK) of a single dose of intravenous (IV) oxytocin and a single dose of intranasal (i.n.) oxytocin.

This is an unblinded study of subjects, all of whom will receive an intravenous (IV) infusion and intranasal (i.n.) dose of oxytocin (a naturally occurring hormone that is made in the brain) with blood samples taken thereafter in order to create a formula to describe the concentrations of oxytocin in the blood over time (pharmacokinetics).

In this study healthy volunteers and people are recruited for a two day study. Each study participant will have 2 IV catheters placed (one in each arm) for the day of IV oxytocin dosing and 1 IV catheter on the day of i.n. oxytocin dosing. After placement of the IV catheters, an infusion of oxytocin will be given over a 30 minute period. Blood samples will be taken after the infusion begins and several times during and after the infusion. The blood will be drawn through the IV catheter not used for the oxytocin infusion. For the intranasal oxytocin administration day, 1 IV catheter will be placed and several blood samples will be taken after administration.

Detailed description:
This is an unblinded, sequential study of subjects; all participants will receive an infusion of oxytocin and intranasal administration of oxytocin with blood samples taken thereafter in order to create a formula to describe the concentrations of oxytocin in the blood over time (pharmacokinetics). In this study healthy volunteers. Participants will come to the Clinical Research Unit (CRU) on study day 1 and have two IVs inserted; one in each arm. Participants will get a 30 minute infusion through one of the IV catheters of oxytocin and blood will be taken several times over the next 120 minutes, plasma separated, and the amount of oxytocin measured in the plasma samples. Participants will come to the CRU on study day 2 and have one IV inserted; in the arm. Participants will self administer intranasal oxytocin and blood will be taken several times over the next 60 minutes and the amount of oxytocin measured in the plasma samples. This information will be analyzed by another group at Stanford University under a data sharing agreement between the institutions and funded by a grant from the National Institutes of Health. Compartmental modeling will be performed using NONMEM to describe the change in oxytocin concentrations over time. The effect of subject age, sex, race, ethnicity and weight on the pharmacokinetics of oxytocin will be examined, since these factors can affect pharmacokinetics and are important to better adjust the dose of drug to the individual.

The main purpose of this study is to determine the amount of oxytocin in plasma after IV and i.n. administration.

The research participants will not benefit from this study, but the knowledge investigators get will be important to adjust oxytocin dose to individuals, and to be able to calculate plasma oxytocin concentrations after various doses in the future. The sample size chosen is needed to get an accurate estimate for the parameters in the pharmacokinetic model for the population, not just the subjects in this study.

Arms:
arm 1: Oxytocin 14 micrograms infusion over 30 minutes on first study day. Oxytocin 102 micrograms by intranasal spray on second study day.

Interventions: intervention 1: intravenous oxytocin intervention 2: intranasal oxytocin
Intervention descriptions: intervention 1: Oxytocin given by intravenous route intervention 2: Oxytocin given by intranasal administration

Protocol document:
Prot_SAP_001.pdf: 
January 27, 2023 
Page 1 of 10 
 
Official Title: A Pharmacokinetic Study of Intravenous and Intranasal Oxytocin in Healthy Subjects 
NCT05672667 
IRB-Approved Date: 1/5/23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


January 27, 2023 
Page 2 of 10 
 
A Study of Oxytocin Pharmacokinetics after Intravenous and Intranasal Administration in Healthy 
Subjects  
 
Principal Investigator: James C. Eisenach, M.D., Co-investigator(s): Douglas Ririe, M.D. 
 
Sponsor or funding source: NIH 
 
Background, Rationale and Context 
 
 
Oxytocin (OXT) uniformly produces antinociception and anti-hyperalgesia in rodents, yet intranasal 
OXT fails to reduce pain in 6 of 13 clinical studies [2]. Three observations from our group suggest that OXT is 
not analgesic in the normal condition, but speeds recovery from pain after injury and prevents the transition 
from acute to chronic pain: 1) The incidence of chronic pain from surgery is considerably lower after cesarean 
section compared to other pelvic surgeries [3], 2) recovery from hypersensitivity after nerve injury is quicker in 
female rats when injury occurs at the time of delivery, an effect temporarily reversed with a nonselective OXT 
and vasopressin 1a (V1a) receptor antagonist [4], and 3) selective antagonists of these receptors temporarily 
reverse recovery from nerve injury in both male and female rodents [5]. 
 
 
OXT itself is the sole readily-available tool to test clinical relevance of basic science studies of 
OXTergic signaling in other neurologic disorders, including pain, neuroprotection during brain ischemia, ADHD 
and autism and in psychiatry, including social behaviors which are positive (trust, neonatal-maternal and adult 
pair bonding) and negative (aggression and ethnocentrism).  Existing clinical studies rely primarily on 
correlations between disease activity and common polymorphisms in OXT receptors or plasma OXT 
concentrations, which are unlikely to reflect OXT release in the brain.   
 
 
Direct evaluation of peripheral and central effects of systemically administered OXT in humans is 
hampered by bolus dosing, lack of dose response, and ignorance of peripheral and central drug distribution, 
especially with intranasal administration. Poor rigor and fundamental ignorance of drug disposition partly 
underlie the uncertainty regarding OXT’s actions in acute and chronic pain. 
 
 
Prior to 2016, and to a considerable extent since, OXT was and 
is measured with antibody-based methods (EIA, ELISA, or RIA).  
Reported concentrations vary widely from study to study and, since 
development of accurate LC/MS assays, there is now considerable 
skepticism regarding the validity of the previous research and concerns 
that the older methods measure OXT degradation fragments (see [6] for 
review).  Note in Figure 1 the high baseline and wide variability in OXT 
concentrations and markedly different change in OXT concentrations 
after intranasal (i.n.) administration when ELISA and RIA methods are 
used compared to that of LC/MS, which unamiguously measures OXT 
[4; 5; 8; 9]. 
 
 
In preliminary data we infused OXT, 17 μg, iv in 11 healthy men 
and women aged 22-58 years, measured plasma OXT with both LC/MS 
and with ELISA using validated protocols, and modeled the resultant data using NONMEM.  Transient 
headache and facial flushing occurred when this dose was injected over 1 min in the first 3 individuals and 
these effects were reduced or eliminated with infusion over 10 min in the remainder of the subjects. PK 
analysis showed no effect of sex and a minor effect of body weight.   Modeled data from the LC/MS analysis 
differ significantly from those using RIA assays after iv OXT injection [2; 7], which themselves differ widely 
(Figure 2A).  In our study, ELISA assays showed more inter-individual variability (NONMEM estimates of 
variance due to assay for ELISA was 28% compared to 16% for LC/MS) and considerably different PK 
parameters than those obtained from LC/MS assays.  Simulated target controlled infusions (TCI) based on 
Figure. 1.  Mean plasma OXT via i.n. 
administration by various assays. 
Plasma OXT (pg/ml) 


January 27, 2023 
Page 3 of 10 
 
these models demonstrate the greater variability with ELISA than 
LC/MS (Figure 2B). At the same total dose of 17 μg OXT, a 30 min 
TCI infusion using PK parameters using LC/MS assays would result 
in a targeted concentration nearly double that using PK from ELISA 
assays (80 vs 46 pg/ml for LC/MS vs ELISA). 
 
 
Defining PK of OXT in plasma after peripheral administration 
is required in order to determine PK / pharmacodynamic (PK/PD) 
relationships for actions centrally, the primary focus for much of 
neuroscience OXT research, and peripherally, the focus of our 
primary hypothesis regarding analgesic and disease-modifying 
effects of OXT in pain after injury.  This requires measuring OXT with 
a reliable, sensitive, and specific assay to define PK and using the 
knowledge of PK to design dosing schemes with reliable measures of 
drug action at sites of interest. It also requires creation of outcome 
measures in the periphery (beyond those peculiar to obstetrics) and 
centrally which can be repeatedly measured at frequent intervals 
adequate for PK/PD modeling.  These are the goals of this clinical 
project within a multi-project NIH proposal (P01-NS119159).  
 
 
I.n. administration is far more practical for subacute and 
chronic treatment, as would be needed in clinical trials, and the 
purpose of the current study is to determine the bioavailability and 
PK of OXT after i.n. administration.  The proposed study utilizes a 
multi-visit, crossover design.  In order to determine bioavailability, 
each subject will receive OXT by intravenous injection on one 
occasion and i.n. on others.  To determine linearity of OXT 
bioavailability across doses to be subsequently studied, two i.n. OXT doses will be administered on different 
occasions.  Subjects will be stratified across three age groups from young adults to the elderly, with balanced 
recruitment by sex in order to assess covariates of age and sex in OXT PK. 
 
Objectives 
Main objective Model OXT concentrations in plasma after intravenous and i.n. administration in order 
to determine absorption rate and bioavailability of OXT in plasma after i.n. administration. 
 
Additional Objectives  
1. Describe adverse events with intravenous and i.n. administration 
 
Methods and Measures 
 
Equal numbers of adult men and women will be recruited. Sample size will be divided into 3 groups; 
young (18-39-year-old) middle (40 – 59-year-old) and older (60 – 75-year-old). 
 
Subjects will report to the CTSI Clinical Research Unit (CRU) for two visits, separated by at least 5 
days.  On study visit one informed consent will be obtained and eligibility verified. Then two intravenous (IV) 
catheters will be inserted, one in each forearm, with one for drug infusion and the other for blood sampling. 
After baseline measures, subjects will receive oxytocin (Pitocin®), 14 μg (8.2 IU) over 30 minutes.  This dose 
and infusion duration were chosen based on previous studies showing no adverse events in 10 volunteers and 
our preliminary PK model which predicts that plasma oxytocin concentrations will be above the limit of 
detection (1 pg/ml) at 120 min. Venous blood samples (5 ml) will be obtained at 2, 5, 10, 20, 30, 40, 50, 65, 90, 
and 120 minutes after the initiation of oxytocin administration for oxytocin assay.  
 
On study visit 2, one IV catheter will be placed for blood sampling. After baseline measures, subjects 
will receive 102 µg (60 IU) intranasal oxytocin (Tonix-1900, Tonix Pharmaceuticals, Chatham, NJ). Venous 
blood samples (5 ml) will be obtained at 1, 2, 5, 7, 10, 15, 20, 25, 35, 45, and 60 minutes after the initiation of 
the oxytocin administration for oxytocin assay.  See graph 3 for rationale for the times of sampling. 
Figure 2. A) PK modeled OXT 
concentrations in preliminary data 
compared with published reports. B) 
Fraction of targeted concentration using 
TCI. 95% prediction intervals from LC/MS 
or ELISA assays of duplicate samples 
(n=11). 


January 27, 2023 
Page 4 of 10 
 
 
We will abandon an individual participant's study 
and schedule another participant should we be unable to 
successfully place the intravenous catheters. 
STUDY DESIGN 
 
This is a sequential study of subjects, all of whom 
will receive, on different occasions, an intravenous 
infusion or intranasal (i.n.) sprays of oxytocin. Blood 
samples will be obtained thereafter in order to create a 
mathematical model to describe the concentrations of 
oxytocin in the blood over time (pharmacokinetics). In this 
study, healthy volunteers are recruited for two study drug 
visits.  They will come to the CRU and have two IV 
catheters inserted, one in each arm for the first study 
visit.  They will receive a 30 minute infusion through one 
of the IV catheters of oxytocin, 14 µg, and blood will be 
obtained at several times over the next 120 minutes and 
the amount of oxytocin measured in the blood samples. 
They will come a second time to the CRU and have one 
IV inserted in their arm and self-administer i.n. oxytocin, 
102 ug over 5 min and blood will be obtained several 
times over the next 60 minutes and the amount of 
oxytocin measured in the blood samples. Plasma 
oxytocin concentrations and individual subject 
characteristics (age, sex, weight, height, race, and 
ethnicity) will be analyzed by another group at Stanford 
University funded under the same NIH grant supporting 
the work at Wake Forest.  The effect of these subject 
characteristics on the pharmacokinetics of oxytocin will be examined, since these characteristics alter 
concentration over time of some drugs.  Should these characteristics alter oxytocin concentrations, we and 
others could adjust the dose of oxytocin to the individual. 
 
The main purpose of this study is to sample blood and calculate the pharmacokinetics of oxytocin. We 
will also assess adverse events during the study. 
 
The research participants will not benefit from this study, but the knowledge we get will be important not 
only to adjust oxytocin dose to individuals, but to study its possible effects on pain in a more precise way by 
controlling the amount of oxytocin in the blood circulation. The sample size we chose is needed to get an 
accurate estimate for the parameters in the pharmacokinetic model for the population in general, not just the 
subjects in this study. 
 
Setting 
 
Study visits will occur on the main campus at Atrium Wake Forest Baptist Health in the Clinical 
Research Unit (CRU).  
 
Subjects selection criteria 
The study will enroll healthy subjects. 
 
Inclusion Criteria 
1. Male or female > 18 and < 75 years of age, Body Mass Index (BMI) <40. 
2. Generally in good health as determined by the Principal Investigator based on prior medical 
history, American Society of Anesthesiologists physical status 1 or 2. 
3. For healthy volunteers, normal blood pressure (systolic 100-140 mmHg; diastolic 60-90 mmHg) 
resting heart rate 45-90 beats per minute) without medication.  For those with hypertension, blood 
pressure controlled with anti-hypertensive medication and with a resting heart rate 45-100 beats per 
minute. 
Figure 3. Simulated PK and blood sampling times  
A) Simulated plasma OXT concentrations (Cp) with IV 
infusion. The proposed sampling times (red circles) 
optimize the informational content to confirm the model 
generated from 11 subjects in an earlier study.  
B) Simulated plasma OXT concentrations (Cp) with I.N. 
self-administration. The proposed sampling times (red 
circles) optimize the informational content to capture the 
absorption rate constant.  The simulated model 
assumed a Cmax of 15 min and 1% bioavailability.  


January 27, 2023 
Page 5 of 10 
 
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 Pitocin® 
2. Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal 
Investigator, would place the subject at increased risk (active gynecologic disease in which 
increased tone would be detrimental e.g., uterine fibroids with ongoing bleeding), compromise the 
subject’s compliance with study procedures, or compromise the quality of the data 
3. Women who are pregnant (positive result for urine pregnancy test at visit 1), women who are 
currently nursing or lactating, women that have been pregnant within 2 years 
4. Subjects with neuropathy, chronic pain (being treated on a daily basis), diabetes mellitus, or 
taking benzodiazepines or pain medications on a daily basis. 
5. Subjects with current or history of ventricular tachycardia, atrial fibrillation or prolonged QT 
interval. 
6. Subjects with past or current history of hyponatremia or at risk for hyponatremia; anyone taking 
thiazide diuretics, loop diuretics, combination diuretics, lithium, carbamazepine, enalapril, Ramipril, 
celecoxib, temazepam, gliclazide, glimepiride, glibenclamide, glipizide, omeprazole, pantoprazole, 
desmopressin, SSRI’s, MAOI, or the recreational drug ecstasy. 
7. Subjects with a known latex allergy. 
8. History of chronic nasal obstruction or local pathology in nostril pathway which, in the opinion of 
the investigator, would prevent appropriate nasal administration of the study drug. 
9.  Use of OTC nasal products (ie. Saline spray, Neti-Pot, etc.) or intranasal corticosteroid 
medications during the study. 
 
 
 
 
Sample Size 
We request permission to study up to 30 
subjects so that we will have 24 evaluable 
subjects, respectively, with complete sampling 
at all time periods. Sample size will be divided 
into 3 groups; young (18-39-year-old) middle 
(40 – 59-year-old) and older (60 – 75-year-old). 
 
Sample size was determined using of bootstrap 
analyses and conventional calculations to 
estimate the pharmacokinetic parameters within 
the desired level of accuracy. Table 1 shows the results of 1000 bootstrap replications of the 
original 11 individuals in the pharmacokinetic study, resampled with N = 11 (the original study size) 
and N = 20. As expected, the estimates are more precise with increasing study size. The mean and 
95% confidence intervals are shown for each parameter. 
 
 
The 95% confidence intervals from the bootstrap are corrected to provide a “best” estimate of 
the true 95% CI using the upper confidence limit (UCL) method of Browne [1].  As described by 
Whitehead [10], the 95% UCL correction is k/χ_(0.95,k)^2 where k is N-1, the number of degrees of 
freedom. As seen in Table 1, the parameters estimated for the initial 11 subjects have a reasonable 
level of certainty (95% CI < 30% of the mean value) for a small study. However, the corrected CI 
range from the bootstrap for an N=11 study is closer to 70%. A study with 20 subjects will estimate 
the parameters within a corrected 95% CI range within 20% of the mean estimated value (Table 1, 
numbers in red). This is sufficient accuracy to inform the subsequent studies.  
Table 1 Bootstrap parameter estimates of PK model.  
Lower
Upper
Cl1
0.98
0.89
1.08
20%
50%
V1
10.2
8.9
11.9
29%
74%
Cl2
0.21
0.18
0.24
29%
74%
V2
7.1
6.1
8.1
28%
70%
Cl1
0.97
0.95
1.01
7%
12%
V1
10.1
9.6
10.6
10%
18%
Cl2
0.20
0.20
0.21
8%
16%
V2
7.0
6.7
7.3
8%
16%
11
20
2.54
1.88
Corrected 
Range
Range
Mean
Correction
N
Parameter
95% Confidence Bound


January 27, 2023 
Page 6 of 10 
 
 
 
Sample size in this study is increased to 24 permit stratifying by age (3 strata), weight (2 strata), 
and sex. A corrected confidence range less 20% (Table 1) implies that mixed effect analysis will 
distinguish covariate effects in the range of 40% in a study with 20 or more subjects. This is the 
range at which the covariate effect may be clinically consequential. In practice, mixed-effects 
analysis with NONMEM is often sensitive to covariate effects smaller than predicted by preliminary 
analyses. 
 
Interventions and Interactions 
Study Visit 1:  The participant will report to the Clinical Research Unit (CRU) of the Wake Forest 
Clinical Translational Science Institute (CTSI), in the morning after having had nothing to eat or drink since 
midnight. 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 a urine 
pregnancy test performed to determine pregnancy status.  Vital signs to include blood pressure (BP), heart rate 
(HR), respiratory rate (Resp) and peripheral oxygen saturation (POX) will be measured and recorded along 
with height and weight.  
Once eligibility has been determined; baseline vital signs (BP, HR, Resp, POX) will be obtained for a 
baseline measurement and then at the following intervals after the infusion has been initiated; 5, 10, 30, 60, 90 
and 120 minutes. Two intravenous catheters will be inserted, one in each arm, and baseline measurements will 
be obtained.  Then 14 μg (8.2 IU) oxytocin (Pitocin®), obtained from the research pharmacy, will be infused 
over 30 min through one of the catheters.  Blood (5 ml) will be sampled from the other catheter at  2, 5, 10, 20, 
30, 40, 50, 65, 90, and 120 minutes after the initiation of oxytocin, placed on ice, plasma separated in a 
refrigerated centrifuge, and stored at -80°C until analyzed for oxytocin concentration. The study will not be 
blinded.  The intravenous catheters will be removed after all data collection and the subject discharged from 
the CRU. The duration for study visit 2 will be approximately 3.5 hours. 
 
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. Baseline vital signs (BP, HR, Resp, POX) will be obtained for a baseline measurement 
and then at the following intervals after the intranasal oxytocin: 10, 20, 30, 60, 90 and 120 minutes. One 
intravenous catheter will be inserted. Oxytocin, 102 μg (Tonix-1900, Tonix Pharmaceuticals, Chatham, NJ), 
obtained from the research pharmacy, will be self-administered in the nasal passages as one metered spray in 
each nostril followed in 5 min by a second metered spray in each nostril.  Blood (5 ml) will be sampled from the 
IV catheter at 1, 2, 5, 7, 10, 15, 20, 25, 35, 45, and 60 minutes after the initiation of the oxytocin administration, 
placed on ice, plasma separated in a refrigerated centrifuge, and stored at -80°C until analyzed for oxytocin 
concentration. The intravenous catheter will be removed after all data collection and the subject discharged 
from the CRU. The duration for study visit 2 will be approximately 3 hours. 
 
Safety and Monitoring: 
 
Assessment of Side Effects:  Peripheral oxyhemoglobin saturation, BP and HR will be measured 
non-invasively before and 5, 10, , 30, 60, 90 and 120 minutes after oxytocin injection and before and 10, 20, 
30, 60, 90 and 120 minutes after the  intranasal administration. Subjects will informed to report any subjective 
sensations during or after oxytocin administration and will be queried at the same intervals as vital sign 
monitoring for any subjective sensations.  At the end of Study Visit 2 the nasal passages will be inspected for 
any localized tissue reaction. 
 
Treatment of Side Effects: Significant cardiorespiratory side effects include: 
a. Decreased BP with symptoms of hypotension (e.g., dizziness or lightheadedness) 
b. Blood pressure or HR changes >20% 
c. Pulse oximetry less than 94% that does not correct with several deep breaths. 
Treatment of BP elevations > 20% of baseline will be treated with labetalol 5-15 mg IV incrementally until BP 
elevation <20% elevated. Treatment of symptomatic hypotension or BP reductions >20% will be treated with 


January 27, 2023 
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incremental ephedrine 5-20 mg, IV. Heart rate (HR) reductions or elevations > 20% of baseline will be treated 
with incremental glycopyrrolate 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.  
 
Regardless of whether any treatment is required, subjects with significant side effects will be monitored 
more frequently (every 5 min for BP and HR; continuously for POX) until symptoms or signs resolve. 
 
Serious adverse events:  In addition to treatment, as described above, and timely reporting as required to the 
DSMC, IRB, and FDA, emergency treatment will be available within the CRU itself.  As such, an ACLS-certified 
health care professional will be on site or within 5 minutes of the CRU during each treatment session, and a 
crash cart containing medicine and equipment for emergency resuscitation, and an automated external 
defibrillator will be located on-site. 
 
Study Stopping Criteria:  Should significant cardiorespiratory or other side effects occur during oxytocin 
administration, the IV infusion or intranasal self-administration will be stopped and the subject treated as 
indicated in Treatment of Side Effects.  Blood samples will be obtained near the time of oxytocin cessation and 
according to the sampling intervals of the study once the side effects are successfully treated or resolve. 
 
The study will be stopped if more than 2 individuals exhibit significant cardiorespiratory side effects or after any 
serious adverse event and future conduct of the study will be determined by recommendations from the 
DSMC, IRB, and FDA. 
 
 
Outcome Measure(s) 
 
 
Primary Outcome Measure 
 
Name: Oxytocin concentration in plasma 
 
Type: Primary 
 
Time Frame: For 120 minutes after the end of the beginning of intravenous oxytocin infusion  
 
Time Frame: For 60 minutes after the administration of the 102 µg intranasal oxytocin 
 
 
Description: Blood will be sampled at specified intervals during and after the IV infusion and after the 
intranasal self-administration.  Plasma will be separated, rapidly frozen, and later analyzed for oxytocin 
concentration.  The oxytocin concentrations will be modeled to describe the pharmacokinetics of oxytocin and 
the bioavailability of oxytocin after i.n. administration.  We will also determine the effect, if any, of the 
covariates sex, age, weight, race, and ethnicity. 
 
  
Analytical Plan 
 
The parameters of the PK model will be fit to the observed plasma concentrations using NONMEM. 
Inter-subject variability (e.g., biological variability) will evaluate additive, proportional, and exponential models. 
Residual intrasubject variability (e.g., noise) will typically require an additive and multiplicative error model. The 
influence of covariates (e.g., age, sex, weight) on model parameters will be analyzed by serial inclusion / 
exclusion, with significance determined by the likelihood ratio test (p < 0.01 if the decrease in -2 log likelihood 
exceeds 6.6 (𝜒0.99 2 , df = 1)). Parameters will be estimated using first-order conditional estimate with - 
interaction. Covariate effects deemed significant by likelihood ratio test will be validated using jackknife 
crossvalidation [3].  Jackknife cross-validation provides an estimate of the utility of the covariate to inform the 
pharmacokinetics in a future individual, rather than merely characterize the pharmacokinetics in the individuals 
from which the model was derived. The jackknife cross-validation divides the data into N subsets. Each subset 
leaves out a single individual. The parameters of the model are re-estimated for each subset with and without 
the covariate being validated. The inaccuracy (mean ((|measured – predicted|) / predicted)), of the model with 
and without the covariate is measured in the excluded individual. The covariate is only included in the final 
model if it the improvement in model accuracy in the N iterations is significantly greater than 0. Jackknife 
crossvalidation helps compensate for NONMEM’s ability to identify very small covariate effects that do not 


January 27, 2023 
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meaningfully contribute to accuracy in future patients. We will study 24 subjects. Bootstrap analysis indicates 
that the confidence interval for studies of 20 individuals using the LC/MS assay will determine the PK 
parameters with a corrected confidence range < 20%. A corrected confidence range less 20% implies that 
mixed effect analysis will distinguish covariate effects in the range of 40% in a study with 20 or more subjects. 
This is the range at which the covariate effect may be clinically consequential. In practice, mixed-effects 
analysis with NONMEM is often sensitive to covariate effects smaller than predicted by preliminary analyses. 
The sample size is increased to 24 to provide stratification by age (3 strata), weight (2 strata), and sex. The 
crossover design permits accurate determination of i.n. bioavailability and dose linearity despite expected high 
inter-subject variability in absorption. 
 
 
Human Subjects Protection 
 
Subject Recruitment Methods 
Healthy subjects will be recruited from our current database of volunteers BG05-468, word of mouth and Be 
Involved website; The research nurses; Regina Curry, RN and Vonda McGee, LPN will conduct the recruitment 
of study subjects.  
 
Potential subjects from the database will be contacted via phone or email, per their request. Potential 
subjects from the Be Involved website will be contacted according to the information they provide.   
 
Informed Consent 
Signed informed consent will be obtained from each subject.  Regina Curry, RN or Vonda McGee, LPN will 
obtain consent. Potential subjects will be consented in the CRU. A private room will be utilized during the 
consent process and all study visits. 
 
Confidentiality and Privacy 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly identify subjects, 
and maintaining all study information in a secure manner.  To help ensure subject privacy and 
confidentiality, only a unique study identifier will appear on the data collection form.  Any collected patient 
identifying information corresponding to the unique study identifier will be maintained on a linkage file, store 
separately from the data.  The linkage file will be kept secure, with access limited to designated study 
personnel.  Following data collection subject identifying information will be destroyed 3 years after closure 
of the study, in confidential shredding disposal bins consistent with data validation and study design, 
producing an anonymous analytical data set.  Data access will be limited to study staff.  Data and records 
will be kept locked and secured, with any computer data password protected.  No reference to any 
individual participant will appear in reports, presentations, or publications that may arise from the study. 
 
Data Sharing Plan 
Plan Description:  Statistical programs in the data analysis will be written in R. The software and anonymized 
data will be included both as digital supplements in the published papers and will be posted on GitHub under 
github.com/StevenLShafer. Interested investigators will be able to reproduce the published analyses from 
these files. Consistent with the posting of software and data to the OpenTCI initiative, the software and de-
identified data will be made available with "no strings attached," enabling investigators to freely use the data to 
inform or supplement additional research without restriction. Data to be made available are oxytocin dose, 
times of sampling (relative to the start of dosing), plasma oxytocin concentrations at those times for each 
subject, and age, weight, and sex for each subject. 
 
 
 
 
Data and Safety Monitoring 


January 27, 2023 
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The principal investigator will be responsible for the overall monitoring of the data and safety of study 
participants.  A Data Safety Monitoring Committee will include Laura Dean, M.D., Associate Professor, 
Section Head Obstetric and Gynecologic Anesthesia and Ashish Khanna, M.D., Associate Professor, 
Anesthesiology. A cumulative report will be sent to the committee to review quarterly and all serious and 
unexpected adverse events will be reported to the committee for review and recommendations. 
 
Volunteer Payment 
Participants will be paid a total of $500 according to the following payment schedule which we have 
used throughout the last 2 cycles of this grant's protocols. We believe that this payment schedule is fair and 
appropriate, paying for each procedure attempted and an additional payment for completion of the entire study.  
 
Study Visit 1: 2 PIV $25/each ($50); $100 for PK sampling 
Study Visit 2: 1 PIV $25; $100 for PK sampling + $225 for completion of study visit 2 PK sampling 
 
Subject must complete all of the above phases to receive this payment. 
 
If 2 PIV’s cannot be placed on Visit 1: subject will be compensated $50 and subject replaced 
 
 
Long-term Follow-up 
Volunteers will be contacted daily for one week and questioned about adverse events from the study. 
 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes will 
be promptly reported by the principal investigator or designated member of the research team to the IRB, 
DSMC and FDA as required by each. 
 
 
References 
 
[1] Browne RH. On the use of a pilot sample for sample size determination. Stat Med 
1995;14(17):1933-1940. 
[2] De Groot AN, Vree TB, Hekster YA, Pesman GJ, Sweep FC, Van Dongen PJ, Van Roosmalen J. 
Bioavailability and pharmacokinetics of sublingual oxytocin in male volunteers. The Journal of 
pharmacy and pharmacology 1995;47(7):571-575. 
[3] Fiset P, Mathers L, Engstrom R, Fitzgerald D, Brand SC, Hsu F, Shafer SL. Pharmacokinetics of 
computer-controlled alfentanil administration in children undergoing cardiac surgery. 
Anesthesiology 1995;83(5):944-955. 
[4] Franke AA, Li X, Menden A, Lee MR, Lai JF. Oxytocin analysis from human serum, urine, and 
saliva by orbitrap liquid chromatography-mass spectrometry. Drug testing and analysis 
2019;11(1):119-128. 
[5] Kirkpatrick MG, Francis SM, Lee R, de Wit H, Jacob S. Plasma oxytocin concentrations following 
MDMA or intranasal oxytocin in humans. Psychoneuroendocrinology 2014;46:23-31. 
[6] Leng G, Sabatier N. Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and 
Random Numbers. J Neuroendocrinol 2016;28(10). 
[7] Nielsen EI, Al-Saqi SH, Jonasson AF, Uvnas-Moberg K. Population Pharmacokinetic Analysis of 
Vaginally and Intravenously Administered Oxytocin in Postmenopausal Women. J Clin 
Pharmacol 2017;57(12):1573-1581. 
[8] Quintana DS, Westlye LT, Rustan ØG, Tesli N, Poppy CL, Smevik H, Tesli M, Røine M, Mahmoud 
RA, Smerud KT, Djupesland PG, Andreassen OA. Low-dose oxytocin delivered intranasally 


January 27, 2023 
Page 10 of 10 
 
with Breath Powered device affects social-cognitive behavior: a randomized four-way 
crossover trial with nasal cavity dimension assessment. Translational Psychiatry 2015;5:e602. 
[9] Striepens N, Kendrick KM, Hanking V, Landgraf R, Wullner U, Maier W, Hurlemann R. Elevated 
cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration 
in humans. SciRep 2013;3:3440. 
[10] Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot 
randomised trial to minimise the overall trial sample size for the external pilot and main trial for 
a continuous outcome variable. Statistical methods in medical research 2016;25(3):1057-1073. 
 

ICF_000.pdf: 
Official Title:  A Pharmacokinetic Study of Intravenous and Intranasal Oxytocin in Healthy Subjects  
NCT05672667
IRB-Approved Date: 2/6/23


Page 1 of 11
Adult Consent Form
1/27/2023
Department/Section of Anesthesiology
A Study of Oxytocin Pharmacokinetics after Intravenous and Intranasal 
Administration in Healthy Subjects
Informed Consent Form to Participate in Research
James C. Eisenach, M.D., Principal Investigator
SUMMARY
You are invited to participate in a research study. The purpose of this research is to evaluate the 
change of oxytocin in the blood after administration of oxytocin by intravenous (IV) route and 
the amount of oxytocin in the blood after intranasal (i.n.) oxytocin is administered.  You are 
invited to be in this study because you are a healthy subject. Your participation in this research 
will involve 2 visits and last approximately 3 to 4 hours per visit. 
Participation in this study will involve IV administration and i.n. administration of oxytocin and 
blood sampling.  All research studies involve some risks.  Risks to this study include discomfort 
or bruising from IV placement, nasal irritation from the oxytocin spray, changes in your blood 
pressure or heart rate from oxytocin which may require treatment, and headache or a feeling of 
flushing from oxytocin. These are more described in the risk section of this consent. 
You may or may not benefit from participation in this study.  
Your participation in this study is voluntary.  You do not have to participate in this study if you 
do not want to.  This is not a treatment study and there are no additional choices. You will not 
lose any services, benefits, or rights you would normally have if you choose not to participate. 
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions if you need help deciding whether to join the 
study. The person in charge of this study is James C. Eisenach, M.D. If you have questions, 
suggestions, or concerns regarding this study or you want to withdraw from the study his/her 
contact information is:  James C. Eisenach, M.D.
   
   
   
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board at 
 or the Wake Forest University 
Health Sciences Research Subject Advocate at 
.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 2 of 11
Adult Consent Form
1/27/2023
INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because you are a healthy adult. Please take your time in making your decision as to 
whether or not you wish to participate. Ask your study doctor or the study staff to explain any 
words or information contained in this informed consent document that you do not understand. 
You may also discuss the study with your friends and family.
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to evaluate the level of oxytocin in the blood after 
administration of oxytocin (naturally occurring hormone made in the brain that transmits 
messages) by intravenous (IV) route and intranasal (i.n.) route. 
Oxytocin has been approved by the US Food and Drug Administration (FDA), but it has not 
been approved for use in this manner, at this dose, for this condition, for administration by this 
route.  
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
In order to identify the 24 subjects needed, we may need to screen as many as 100 because some 
people will not qualify to be included in the study.
WHAT IS INVOLVED IN THE STUDY?
You will have 2 study visits. All study visits will be conducted in the Clinical Research Unit (CRU) 
at Atrium Health Wake Forest Baptist Health. The first study visit will last approximately 4- 5 
hours and the second study visit will last approximately 2-3 hours.
If you take part in this study, you will have the following tests and procedures:
PROCEDURES
Vital Signs: we will monitor your blood pressure, heart rate, respiratory rate and oxygen 
saturation (amount of oxygen in your blood).  
Laboratory Testing: female participants of child-bearing potential will provide a urine 
sample to determine that they are not pregnant. 
Intravenous injection of Oxytocin: we will place an intravenous catheter and administer a 
dose of oxytocin. 
Intranasal Oxytocin: you will administer oxytocin spray into each side of your nose. 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 3 of 11
Adult Consent Form
1/27/2023
Blood Sampling for Oxytocin amounts: we will place a second intravenous catheter for 
taking a small sample of your blood (1 teaspoon) at multiple times through the visits.
You will have approximately 1 teaspoon of blood withdrawn from a vein 10 times at visit 1 and 
11 times at visit 2. Total amount of blood withdrawn during the study (including both study 
visits) will be approximately 8 tablespoons.
Study Visit 1
You will report to the Clinical Research Unit (CRU) at Atrium Health Wake Forest Baptist, in the 
morning after having had nothing to eat or drink since midnight. You will review and sign the Informed 
Consent. After informed consent is adequately obtained, a detailed medical history will be obtained, 
female participants of child bearing potential will have a urine pregnancy test performed to determine 
pregnancy status.  Vital signs will be taken including blood pressure (BP), heart rate (HR), respiratory 
rate (Resp) and peripheral oxygen saturation (POX) will be measured and recorded along with height and 
weight. 
Once eligibility has been determined; two intravenous catheters will be inserted, one in each arm, 
baseline vital signs (BP, HR, Resp, POX) will be obtained before the initiation of the infusion and then at 
the following intervals after the infusion has been initiated; 5, 10, 30, 60, 90 and 120 minutes.  Then 14 
micrograms oxytocin (Pitocin®), will be obtained from the research pharmacy, and infused over 30 min 
through one of the catheters.  Blood (1 teaspoon) will be sampled from the other catheter at 2, 5, 10, 20, 
30, 40, 50, 65, 90, and 120 minutes from starting the infusion. The intravenous catheters will be removed 
after all data collection and you will be discharged from the CRU. The duration for study visit 1 will be 
approximately 4 hours.
Study Visit 2 
On the second visit, you will report to the CRU, in the morning after having had nothing to eat or 
drink since midnight. Vital signs (BP, HR, Resp, POX) will be obtained for a baseline measurement and 
then at the following intervals after the intranasal oxytocin: 10, 20, 30, 60, 90 and 120 minutes. One 
intravenous catheter will be inserted. Then you will self-administer oxytocin obtained from the research 
pharmacy, by nasal spray.  For this you will administer one spray in each nostril and 5 minutes later, one 
more spray in each nostril.  The total dose is 102 micrograms.  Blood (1 teaspoon) will be sampled from 
the IV catheter at 1, 2, 5, 7, 10, 15, 20, 25, 35, 45, and 60 minutes after the administration of the oxytocin. 
The intravenous catheter will be removed after all data collection and you will be discharged from the 
CRU. The duration for study visit 2 will be approximately 3 hours.
HOW LONG WILL I BE IN THE STUDY?
You will be in the study for 2 visits, approximately 7 hours total.
We will contact you daily for 7 days after each study visit to ask how you are doing.
You can stop participating at any time. If you decide to stop participating in the study, we 
encourage you to talk to the investigators or study staff first. 
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. Risks and side effects related to this study and oxytocin include:
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 4 of 11
Adult Consent Form
1/27/2023
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.  
Oxytocin
Intravenous oxytocin is not approved by the Food and Drug Administration (FDA) for use in 
men or in women other than in obstetric and certain gynecologic indications and intranasal 
oxytocin is not approved by the FDA for any indication.  This study is being performed under 
Investigational New Drug oversight by the FDA.  We will monitor you for many possible 
problems such as changes in your blood pressure, how fast your heart is beating, and your urge 
to breathe. We will treat any side effects that you may experience if the changes are enough to 
concern us.
There is the possibility of a feeling of being flushed (warm feeling), headache and increased 
heart rate with no significant change in blood pressure during or immediately after the infusion. 
These events have been reported by previous participants but were short lived, lasting 
approximately 12-15 minutes.
In addition, there is a slight risk of a breach of confidentiality.  We will do our best to protect 
your confidential information.  There also may be other side effects that we cannot predict. You 
should tell the research staff about all the medications, vitamins and supplements you take and 
any medical conditions you have. This may help avoid side effects, interactions and other risks.
Taking part in this research study may involve providing information that you consider 
confidential or private.  Efforts, such as coding research records, keeping research records secure 
and allowing only authorized people to have access to research records, will be made to keep 
your information safe.
Blood Draws
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.  Frequent donation of blood can result in low iron in your blood (iron deficient 
anemia).  
If you donate blood to the American Red Cross, you should talk with the study doctor about 
whether or not it is safe to do so while participating in this study. You should not donate blood 
more than 2 times per week and no more than approximately one pint (about 500 ml) of blood in 
an eight week period.
There also may be other risks 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 to your health.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 5 of 11
Adult Consent Form
1/27/2023
A Data Safety and Monitoring Committee, an independent group of experts, will be reviewing 
the data from this research throughout the study to identify possible safety issues to participants 
and to provide advice and recommendations on possible changes to the research study for the 
protection of participants.
Reproductive Risks and other Issues to Participating in Research
Due to unknown risks and potential harm to the unborn fetus, sexually active women of 
childbearing potential must use a reliable method of birth control while participating in this 
study. Reliable methods of birth control are: abstinence (not having sex), oral contraceptives, 
OrthoEvra patch, NuvaRing, intrauterine devices (IUD), Nexplanon implant, 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 diaphragm with spermicide with Plan B 
used for any noticed condom or diaphragm failures. We encourage you to discuss this issue 
further with your physicians if you have any questions.
Pregnant women are excluded from participation in this study. Because NO method of birth 
control is 100% reliable, a pregnancy test is required at least 10 days from your last normal 
menstrual period, if you are a sexually active woman of childbearing potential.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
You are not expected to receive any direct benefit from taking part in this research study. We 
hope the information learned from this study will benefit other people in the future.
WHAT OTHER CHOICES ARE THERE?
This is not a treatment study. Your alternative is to not participate in this study.
WHAT ARE THE COSTS?
All study costs, including any study products or 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 or permitted by law, or necessary to protect the safety of 
yourself or others.  
Your 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.
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 6 of 11
Adult Consent Form
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_________ Please initial if you agree to the following statement for text messaging contact
TEXT MESSAGE COMMUNICATION. I give permission to Atrium Health, Wake Forest 
University Health Sciences, and their respective affiliated entities and representatives (including 
third-party agents if applicable) to contact me by text message at the number I provided to send 
information, reminders, and to communicate with me about the research study. I understand that 
I am responsible for the standard text message rate of my carrier. I also understand that text 
messaging is not a secure form of communication and I accept the risk that individuals not 
involved in the research study may be able to access the text messages.  I also understand that 
texting is not to be used for emergency situations.  
__________ Please initial if you agree to the following statement for email contact
EMAIL COMMUNICATION. By providing my email address, I give permission for Atrium 
Health, Wake Forest University Health Sciences, and their respective affiliated entities and 
representatives (including third-party agents if applicable) to send me information, reminders, 
and messages about the research study by email. I understand that these email messages may not 
be encrypted, and I understand and accept the risks that individuals not involved in the research 
study may be able to access unencrypted email messages. I also understand that email is not to be 
used for emergency situations. 
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health. This means that the researchers cannot release or use information, documents, or samples 
that may identify you in any action or suit unless you say it is okay. They also cannot provide 
them as evidence unless you have agreed.  This protection includes federal, state, or local civil, 
criminal, administrative, legislative, or other proceedings. An example would be a court 
subpoena.
 
There are some important things that you need to know.  The Certificate DOES NOT stop 
reporting that federal, state or local laws require. Some examples are laws that require reporting 
of child or elder abuse, some communicable diseases, and threats to harm yourself or 
others.  The Certificate CANNOT BE USED to stop a sponsoring United States federal or state 
government agency from checking records or evaluating programs. The Certificate DOES NOT 
stop disclosures required by the federal Food and Drug Administration (FDA).  The Certificate 
also DOES NOT prevent your information from being used for other research if allowed by 
federal regulations.
 
Researchers may release information about you when you say it is okay. For example, you may 
give them permission to release information to insurers, medical providers or any other persons 
not connected with the research.  The Certificate of Confidentiality does not stop you from 
willingly releasing information about your involvement in this research. It also does not prevent 
you from having access to your own information. 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 7 of 11
Adult Consent Form
1/27/2023
WILL YOU BE PAID FOR PARTICIPATING?
You will be paid $500 if you complete all the scheduled study visits. If you withdraw for any 
reason from the study before completion you will be paid according to the description below.
  
Study Visit 1: 2 PIV $25/each ($50); $100 for PK sampling
Study Visit 2: 1 PIV $25; $100 for PK sampling + $225 for completion of study visit 2 PK 
sampling
If 2 peripheral intravenous catheters cannot be placed on Visit 1 you will be compensated $50 
and we will not be able to include you in the study. 
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 the researchers 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?
Wake Forest University Baptist Medical Center maintains limited research insurance coverage 
for the usual and customary medical fees for reasonable and necessary treatment of injuries or 
illnesses to some participants in certain research studies. 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.  To the extent research coverage is not available, you 
or your insurance company may be charged for the costs of medical care. You may receive care 
at Wake Forest University Baptist Medical Center and/or Atrium Health.
If you are injured, the insurer may require information such as your name, social security 
number, and date of birth in order to pay for your care.  This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call James Eisenach at
 or after hours 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 8 of 11
Adult Consent Form
1/27/2023
you should call the study coordinator at 
.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you about your health or behaviors 
is considered Protected Health Information. The information we will collect for this research 
study includes: medical history and medication history.
If this research study involves the diagnosis or treatment of a medical condition, then Protected 
Health Information collected from you during this study may be placed in your medical record, 
and may be used to help treat you, arrange payment for your care, or assist with the health care 
operations of Atrium Health, Wake Forest University Health Sciences, and their respective 
affiliated entities. 
We will take steps to keep your Protected Health Information private. We will store records of 
your Protected Health Information in a cabinet in a locked office or on a password protected 
computer. 
Your personal health information and information that identifies you (“your health information”) 
may be given to others during and after the study. This is for reasons such as to carry out the 
study, to determine the results of the study, to make sure the study is being done correctly, to 
provide required reports and to get approval for new products.  
Some of the people, agencies and businesses that may receive and use your health information 
are the research sponsor; representatives of the sponsor assisting with the research; investigators 
at other sites who are assisting with the research; central laboratories, reading centers or analysis 
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and Atrium Health Facilities; representatives from government agencies such as the 
Food and Drug Administration (FDA) or the Office of Human Research Protections (OHRP), the 
Department of Health and Human Services (DHHS), the National Institutes of Health (NIH) 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, 
videotapes, audiotapes or other recorded media which are identify you unless we you’re your 
written authorization.
Monitors, auditors, IRB or other regulatory agencies will be granted direct access to your 
medical record for verification of clinical trial procedures or data to the extent permitted by other 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 9 of 11
Adult Consent Form
1/27/2023
applicable laws.  These monitors, auditors, and other individuals are also required to maintain the 
confidentiality of your protected health information.
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.
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 Atrium Health, Wake Forest 
University Health Sciences, or their respective affiliated entities 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.  Authorization to 
access this part of the medical record will only be available to people who have a need to know 
this information in order to perform their job-related duties.  If you are not a patient of these 
health care facilities, a medical record will be created for you anyway to provide access to this 
important information to providers 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. 
As part of the Clinical Trials Registry, a Data Sharing Plan will be included on the website. The 
following data will be made available are oxytocin dose administered, time blood sampling 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


Page 10 of 11
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occurred (relative to the start of dosing), plasma oxytocin concentrations at the sampling times 
for each subject, and age, weight, and sex for each subject.
Laboratory test results and other clinically relevant medical reports created as a result of your 
participation in the research study may be entered into the computer systems of Atrium Health, 
Wake Forest University Health Sciences, and/or their respective affiliated entities.  These results 
and reports will be kept secure in compliance with applicable laws, with permission to access 
this information limited to individuals with proper authority, but who may not be directly 
involved with this research study.
A medical record will be created for all study participants seen on-site and if a medical record 
doesn’t already exist. Information about your participation in the study will be placed in the 
medical record, along with any routine medical test results that were obtained as part of this 
study. 
WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
at any time. This could be because it is in your best medical interest, new information becomes 
available, you had an unexpected reaction, you failed to follow instructions, or because the entire 
study has been stopped. Information that identifies you may be removed from the data or 
specimens that are collected as part of this study and could be used for future research or shared 
with others without additional consent.
You will be given any new information we become aware of that would affect your willingness 
to continue to participate in the study.
This study will be enrolling students from Atrium Health and Wake Forest University School of 
Medicine.  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 student, please contact the research subject advocate 
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 
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023


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investigator, Dr. James Eisenach at 
 or after hours you should call the study 
coordinator by calling 
.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
 or the 
Research Subject Advocate at 
.
You will be given a copy of this signed consent form. 
SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form.  If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me.  I have had a chance to 
ask questions about being in this study and have those questions answered.   By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):____________________________________
Subject Signature: ____________________________________________________________ 
Date: _______________ Time: ______________ am pm 
Person Obtaining Consent (Printed):_________________________________________
Person Obtaining Consent: ______________________________________________________ 
Date: _______________ Time: ______________ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00089938
Meeting Date Approved 2/6/2023          
Version Valid Until: 11/28/2023