Clinical trial NCT04556552
Conditions: Substance-Related Disorders Substance Use Disorders Substance Abuse, Intravenous Substance Withdrawal Substance Abuse Opioid-use Disorder Opioid Use Disorder, Severe Opioid Use
Keywords: opioid use disorder vagus nerve vagal nerve neuromodulation vagus nerve stimulation OUD
Sponsor: Emory University
Start date: 2020-11-13; Completion date: 2022-09-13
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Subjects in this study will be patients with opioid use disorders (OUDs) based on DSM-5 criteria recruited from the greater Atlanta metropolitan region. Recruitment will be from treatment programs in the greater Atlanta Metropolitan Region including the DeKalb Community Service Board residential, detoxification and other treatment programs which with over 30,000 patient visits per year represents the largest treatment program in one of two urban counties in greater Atlanta.

This trial involves a second phase after completing an exploratory study in 20 patients with OUDs to assess different timing parameters of nVNS effects on sympathetic measures and symptoms of craving, as well as modelling to verify and iteratively refine the methods for vagal nerve stimulation. The investigators in this trial will then apply nVNS comparing active (N=10) to sham (N=10) in OUD patients recently started on medication, looking at opioid craving, brain functional response with HR-PET, and cardiovascular and inflammatory biomarker responses to imagery-induced opioid drug craving.

Detailed description:
Subjects in this study will be patients with opioid use disorders (OUDs) based on DSM-5 criteria recruited from the greater Atlanta metropolitan region. The metropolitan Atlanta area has about 2,623,744 persons age 12 or older. According to the Substance Abuse and Mental Health Services Administration (SAMHSA), 109,777 (4.18%) have non-medical use of prescription pain relievers, and 48,302 are estimated to have an opioid use disorder. This DSMP describes the UG3 phase which will study patients with OUDs early in the course of treatment. The Go-No Go criteria listed below have to be met to proceed to the UH3. Recruitment will be from treatment programs in the greater Atlanta Metropolitan Region including the DeKalb Community Service Board residential, detoxification and other treatment programs which with over 30,000 patient visits per year represents the largest treatment program in one of two urban counties in greater Atlanta.

The first UG3 phase will involve an exploratory study in 20 patients with OUDs to assess different timing parameters of nVNS effects on sympathetic measures and symptoms of craving, as well as modelling to verify and iteratively refine our methods for vagal nerve stimulation. The investigators in this trial will then apply nVNS in a pilot study comparing active (N=10) to sham (N=10) in OUD patients recently started on medication, looking at opioid craving, brain functional response with HR-PET, and cardiovascular and inflammatory biomarker responses to imagery-induced opioid drug craving. Brain function will be measured with high resolution positron emission tomography (HR-PET), autonomic function with wearable sensing devices, and biomarkers will be measured in blood, with an assessment of a broad range of stress responsive sympathetic, hormonal and immune markers.

Arms: arm 1: Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues. arm 2: Sham stimulation of vagus with opioid cues
Interventions: intervention 1: Non invasive VN stimulation (nVNS) intervention 2: Oxygen (15-O) Water intervention 3: Sham Stimulation
Intervention descriptions: intervention 1: Stimulation of vagus nerve with active device. Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.

The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained. intervention 2: Injection of radiolabelled water. H2\[15-O\] is a radioactive material. Each patient will have eight H2\[15-O\] blood flow scans. For each O-15 water scan 20 mCi of H2\[15O\] will be injected as an intravenous bolus. intervention 3: Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.

Protocol documents:
Prot_SAP_001.pdf: 
Study Protocol
Title: Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders
NCT04556552 
Date: 7.18.2022


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PROTOCOL TITLE:
Non-invasive Vagal Nerve Stimulation in Opioid Use Disorders 
PRINCIPAL INVESTIGATOR:
J Douglas Bremner, MD
SOM/Psychiatry
 
VERSION NUMBER/DATE:
Version 11/7.18.2022
REVISION HISTORY
Revision 
#
Version Date
Summary of Changes
Consent 
Change?
1
12/15/19
New
new
2
1/6/2020
Requested changes from IRB and M. Huber
Yes
3
1/29/20
Response by PI
No
4
9/25/2020
Add MRI, study updates
Yes
5
10/9/2020
Compensation changes – check or ClinCard
Yes
6
11/5/2020
Revised exclusion criteria
Yes
7
11/23/2020
Compensation updates
Yes
8
1/20/2021
Updating psychiatric testing
No
9
3/29/2021
Update assessments, add follow up call
Yes
10
10/14/2021
Revise inc/exc wording
No
11
7/18/2022
Revise eligibility
Yes


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Table of Contents
1.0
Study Summary ........................................................................................................3
2.0
Objectives* ...............................................................................................................4
3.0
Background*.............................................................................................................4
4.0
Study Endpoints*......................................................................................................5
5.0
Study Intervention/Investigational Agent.................................................................5
6.0
Procedures Involved* ...............................................................................................6
7.0
Data and Specimen Banking*.................................................................................13
8.0
Sharing of Results with Participants*.....................................................................13
9.0
Study Timelines*....................................................................................................14
10.0
Inclusion and Exclusion Criteria* ..........................................................................14
11.0
Vulnerable Populations*.........................................................................................15
12.0
Local Number of Participants.................................................................................15
13.0
Recruitment Methods..............................................................................................15
14.0
Withdrawal of Participants* ...................................................................................16
15.0
Risks to Participants* .............................................................................................16
16.0
Potential Benefits to Participants*..........................................................................20
17.0
Data Management* and Confidentiality.................................................................20
18.0
Provisions to Monitor the Data to Ensure the Safety of Participants* ...................22
19.0
Provisions to Protect the Privacy Interests of Participants .....................................24
20.0
Economic Burden to Participants ...........................................................................24
21.0
Consent Process......................................................................................................24
22.0
Process to Document Consent in Writing...............................................................25
23.0
Setting.....................................................................................................................25
24.0
Resources Available ...............................................................................................26
25.0
Multi-Site Research when Emory is the Lead Site*...............................................33


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1.0
Study Summary
Study Title
Non-invasive Vagal Nerve Stimulation in Opioid Use 
Disorders
Study Design
Sham controlled, two groups
Primary Objective
Map physiology of vagal nerve stimulation in patients with 
OUDs
Secondary Objective(s)
Study #1 maps effect of varying durations of vagal nerve 
stimulation (nVNS) on craving and sympathetic function; 
Study #2 explores neurophysiology of nVNS or sham 
stimulation paired with drug cues.
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
Study #1 involves open label dose finding (varying durations 
of nVNS). Study #2 involves randomization to non-invasive 
vagal nerve stimulation (nVNS) or sham control stimulation 
with assessment of brain, behavioral, physiological, and 
biomarker responses to drug cues and/or craving.
IND/IDE # 
IND 52220
Study Population
Men and women with a history of Opioid Use Disorders 
(OUDs) 
Sample Size
N=20 for study 1 and n=20 for study 2
Study Duration for 
individual participants
2-3 study visits, 6 week follow up call
Study Specific 
Abbreviations/ 
Definitions 
Non-invasive Vagal nerve stimulation (nVNS or VNS), Opioid 
Use Disorders (OUDs)


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2.0
Objectives*
2.1
The purpose of this study is to measure neural and biomarker 
correlates of vagal nerve stimulation (VNS) in men and women with 
a history of Opioid Use Disorders (OUDs). In the UG3 phase we will 
have two studies, Study #1 will be to optimize dosing (N=20) and 
Study #2 to measure brain and biological correlates of nVNS versus 
sham in conjunction with exposure to drug use cues (N=20). We will 
proceed to the UH3 phase which is a larger study in OUD patients if 
the goals of the UG3 phase are met per NIDA. Only the UG3 phase is 
covered here.
2.2
Brain function will be measured with positron emission tomography 
(PET) and biomarkers will be measured in blood, with an 
assessment of a broad range of stress responsive sympathetic, 
hormonal and immune markers
2.3
We hypothesize a decrease in sympathetic function and enhanced 
anterior cingulate function with VNS. 
3.0
Background*
3.1
Opioid Use Disorders (OUDs) are highly prevalent and potentially 
lethal conditions (21). OUDs are often linked to trauma and 
posttraumatic stress disorder (PTSD) (2-20) and limited treatment options 
exist (21-25) the use of nVNS in this project during the opioid withdrawal 
period represents a new innovation from the current treatments using 
medication and counseling, widely acknowledged to have limitations for 
this critical period (26-31). Treatments are needed that address the 
underlying neurobiology of OUDs involving the sympathetic nervous 
system, inflammation, and brain areas and systems mediating craving 
and addiction like dopamine and the anterior cingulate, all potential 
targets of VNS (32-68, 73-94). VNS is effective for a number of conditions, 
including depression and epilepsy (69-72) and is effective for the 
underlying neurobiology of OUDs (96-244). Earlier generations of VNS 
devices had limited implementation due to the requirement for surgical 
implantation, cost, inconvenience, and the inability to do placebo 
comparisons related to ethical considerations (95). The failure of 
Medicare and therefore other insurance agencies to reimburse for VNS 
implantation has been a major limitation to date (95). Further innovation 
lies in the use of HR-PET imaging of the brain with equivalent resolution 
but lacking technical challenges related to interference of VNS electrical 
signal with scan acquisition using magnetic pulses seen with fMRI. Use of 
wearable sensing devices for measurement of sympathetic and 
parasympathetic function and modelling approaches for verification and 


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exploration of stimulation parameters represent additional innovations 
made possible by our collaborations with the Georgia Institute of 
Technology and the City University of New York. We have a multi-
disciplinary and diverse research team of investigators with expertise in 
engineering, computer sciences, behavior, radiology, modelling, nuclear 
physics, neuroimmunology, psychiatry, epidemiology, cardiology and 
biostatistics.
3.2
Our preliminary data on the effects of non-invasive Vagal Nerve 
Stimulation (nVNS) on stress response in traumatized human 
subjects and patients with posttraumatic stress disorder (PTSD) 
show that nVNS reliably blocks peripheral sympathetic and 
enhances parasympathetic function, reduces inflammatory 
responses (interleukin-6, or IL-6), and enhances central brain 
responses (anterior cingulate) to stress (72). We now propose to 
apply this technology to the treatment of patients with OUDs. 
Following verification using modelling and determination of optimal 
dosing parameters, we will use these parameters to assess effects 
of nVNS versus sham stimulation on opioid craving, peripheral 
autonomic, cardiovascular, inflammatory, and brain functional 
responses measured with High-Resolution Positron Emission 
Tomography (HR-PET) and radiolabeled water to videos of drug 
cues in recently treated patients with OUDs.
3.3
This project will assess a new device, non-invasive Vagal Nerve 
Stimulation (nVNS), that does not require surgery or implantation, 
and that electrically stimulates the vagus nerve as it passes through 
the neck, dampening the sympathetic nervous system and 
modulating brain regions in a way that may help patients during the 
opioid withdrawal period and reduce relapse. Studying the effects 
of nVNS on opioid craving and brain and physiological responses in 
patients with OUDs has the potential to reduce relapse and save 
lives, as well as increase our knowledge of changes to the brain and 
physiology that underlie OUDs and successful response to 
treatment. 
4.0
Study Endpoints*
4.1
The primary study endpoint is subjective drug craving and change in 
neurophysiological variables (enhanced anterior cingulate function, 
increased pre-ejection period (PEP) and photoplethysmogram (PPG) 
amplitude, both indicating decreased sympathetic function.
5.0
Study Intervention/Investigational Agent
5.1
Description: This study assesses nVNS versus a sham stimulation 
effects on behaviors of drug craving with and without exposure to 


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drug cues as well as brain response, neurophysiology and 
biomarkers. NVNS is applied to the neck and electrically stimulates 
one of the cranial nerves (the vagus) as it passes through the 
carotid sheath, exerting effects centrally in the brain and 
peripherally on autonomic and inflammatory function
5.2
Drug/Device Handling: Active nVNS and sham control are kept by 
research staff under lock and key and only used for the purposes of 
the study under supervision of the research coordinator.
5.3
The nVNS device has been approved by the Emory IRB for use in a 
current study in patients with PTSD. It is non-invasive with 
minimum side effects and has been shown to be well tolerated and 
there have been no adverse events or untoward effects in 56 
subjects to date.
6.0
Procedures Involved*
6.1
Study Design: Study #1: This is a randomized dose finding study of 
nVNS versus sham stimulation in patients with a history of Opioid Use 
Disorders (OUDs). This study will optimize dosing (N=20) by testing 
different stimulation duration parameters. We will measure how these 
different parameters affect drug craving using analogue scales (248) as 
well as physiological signals with wearable sensing devices.
6.2
Study #2 is also in patients with OUDs whose aim is to measure brain and 
biological correlates of nVNS versus sham in conjunction with exposure 
to drug use cues (N=20). Active and sham devices are assigned serial 
numbers by ElectroCore Inc. and delivered to the Data Manager who 
keeps the blind and assigns to subjects as they are recruited using a 
random number generator. Subjects then undergo nVNS or sham over 
one day in conjunction with control neutral versus drug use videos to 
stimulate craving in conjunction with nVNS or sham with brain imaging, 
measurement of biomarkers and collection of wearable sensing device 
data. We proceed to the UH3 phase which is a larger study in OUD 
patients if the goals of the UG3 phase are met per NIDA. Only the UG3 
phase is covered here. We hypothesize a decrease in sympathetic 
function and interleukin 6 (IL-6, an inflammatory marker) enhanced 
anterior cingulate function with VNS.
6.3
All subjects undergo assessment with behavioral measures, 
including the SCID (245, 246), a craving measure called the Clinical Opiate 
Withdrawal Scale (COWS) (248), the SHAPS-C, NRS pain scale, Addiction 
Severity Index, The Snaith Hamilton Pleasure Scale-Clinician (251), the 
Subjective Units of Distress Scale (263) The Visual Analogue Scale (VAS) 
consists of 10-point lines anchored with "not at all" on one end and 


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"extremely" on the other where participants report the extent to which 
they felt any craving for opiates, severity of withdrawal symptoms, and 
the extent to which the study intervention has helped to ease the 
cravings. 
Medical History, is taken with a structured questionnaire which assess 
socio-demographic factors, medical history, handedness, history of 
substance use, medications including antidepressants, mood stabilizer 
and antipsychotics, usage will be quantitated for number of years of 
usage for utilization in additional analyses. Urine drug testing may be 
done at study visits. The Early Trauma Inventory (ETI) is 56-item 
instrument for measurement of childhood traumatic experiences which 
has been shown to be reliable and valid. All subjects will be assessed with 
both the ETI-SF-SR for events before the age of 18 and the Adult Trauma 
Inventory (ATI) for after age of 18. Reinforcement Learning Task (Positive 
and Negative Valence Domain): Measures reward attainment using an 
instrumental conditioning task (90 trials). Trials for this task involve a 3s 
cue presentation during which subjects choose between two abstract 
stimuli, followed by an exponentially jittered delay, and then a 3s 
feedback presentation with positive (monetary win), negative (monetary 
loss) or neutral outcomes. Reward Motivation Task (Positive Valence 
Domain): Effort-Expenditure for Rewards Task (EEfRT) is a multi-trial 
game in which participants are given an opportunity on each trial to 
choose between two different task difficulty levels in order to obtain 
monetary rewards. 
Study #1: Description of Research Procedures, Monitoring for Safety and 
Minimization of Risks: Patients with OUDs will undergo stimulation at the 
different parameters outlined. Subjects will first be outfitted with 
wearable sensing devices (patches attached to the chest and arms) for 
measurement of physiological signals including the electrical rhythm of 
the heart (electroencephalogram) as shown in the figures. These figures 
outline how parameters of interest like PEP and PPG amplitude are 
measured. Craving is measured with visual analogue scales. Patients will 
undergo VNS or sham stimulation while viewing neutral and opioid use 
related videos.
6.4
Magnetic Resonance Imaging (MRI) of the Brain: Subjects in both 
Study #1 and Study #2 will undergo MRI brain imaging at CSI for 
identification of the vagus nerve in the neck. Sequences to be obtained 
include volumetric interpolated breath-hold examination (VIBE), TR=4.93, 
TE=2.46, flip angle=9, Field of View 210 mm, 112 slices, voxel .78 x .78 x 
.8, averages 3, time of acquisition 4:38. 3D constructive interference in 
steady state (CISS), TR=5.46, TE=2.43, flip angle=42, Field of View 152 
mm, 112 slices, voxel .6 x .6 x .6, averages 1, time of acquisition 5:17.


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6.5
For Study #2 we 
look at physiology 
with nVNS or sham 
in OUD patients. 
Brain function will 
be measured with 
high resolution 
positron emission 
tomography (HR-
PET) (264-270), 
autonomic function 
with wearable 
sensing devices, and 
biomarkers will be 
measured in blood, 
with an assessment 
of a broad range of 
stress responsive 
sympathetic, 
hormonal and 
immune markers. A 
complete outline of study procedures for Study #2 is presented in Figure 
4.
After initial set up and rest period subjects will rest for 30 min. Next, 
subjects will undergo a series of viewing exercises while lying in the High 
Resolution Positron Emission Tomography (HR PET) scanner with 
physiologic monitors attached. After an initial baseline period of resting 
(condition 1), the subjects will then view two neutral 120 second videos 
(condition 2), followed by a playback of two opioid use related videos 
(condition 3). The subject will be instructed 
to image each event as vividly as possible. 
VNS or sham will be randomized and given 
during exposure to the videos. For two of the 
scans, we are looking at effects of nVNS on 
the brain with no intervention. The subjects 
will undergo nVNS vs. Sham VNS stimulation 
as per published methods (see above). 
The VAS and SUDS and other behavioral 
measures are assessed in the beginning and 
after each task to assess the efficacy of the 
Figure 2: Measurement of physiological signals using wearable sensing devices in conjunction with 
nVNS/sham in human subjects. nVNS or sham are attached with a strap to the neck and for electrical 
stimulation of the vagus nerve as it passes through the carotid sheath. Electrocardiogram (ECG) 
and seismocardiogram (SCG) are placed on the chest for measurement of heart function and 
photoplethysmogram (PPG) placed on the finger measures blood volume/peripheral 
vasoconstriction. The ECG measures the distance on a beat-by-beat basis of the R wave interval 
(ventricular depolarization, which allows measurement of heart rate (HR) and with SCG pre-
ejection period (PEP) as described in Figure 3). Sensing devices on the hand measure electrodermal 
activity (EDA), with output of skin conductance level (SCL), a marker of sympathetic function. A 
band on the chest measures respiratory rate (RR), width (RW), and prominence (RP) which tracks 
parasympathetic function. Data is reduced and analyzed and machine learning models are applied 
to predict the stimulation type (nVNS or sham). Subjects also undergo brain imaging with High 
Resolution sPositron Emission Tomography (HR-PET) in Study #2 and magnetic resonance imaging 
(MRI) of the brain in both studies
Figure 3. ECG measures electrical activity of 
the heart (See Fig. 2) and SCG measures 
chest wall movements used to register cardiac 
function including Aortic valve opening (Ao). 
The time interval between the R wave and Ao 
is PEP, which shortens with increased 
cardiac sympathetic tone. The difference in 
PPG amplitude (see Fig. 2) between time 
points measures vasoconstriction, an 
indicator of increased sympathetic function. 


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trauma recall task in eliciting stress. Patients will stay at the Emory 
University Center for Systems Imaging while they are undergoing detailed 
autonomic monitoring and sampling of blood biomarkers. The blood 
draws will occur at baseline, 15 minutes before the drug cue task, during 
the task itself, and then 15, 30, 45, 60, 90, and 120 minutes post-task.
The “VNS” group will be administered nVNS using the electroCore 
GammaCore-S non-invasive VNS device. The intensity of the stimulus (i.e. 
the current amplitude) will be adjusted by the user, to the maximum 
tolerable level to ensure nVNS without causing excessive pain (typically 
10-30 V), the burst frequency to 5 kHz, and the envelope frequency to 25 
Hz. These are the standard frequency settings that electroCore has 
demonstrated to be most effective in capturing the vagus nerve based on 
evoked potential studies. The duration of delivery will be 2 minutes, and 
the beginning will coincide with initiation of acquisition of the HR-PET 
scan which will be 90 seconds in duration; following an additional 8 
minutes, a second VNS delivery will be administered, in conjunction with 
which another scan will be obtained. Each subject in the “SHAM” group 
will undergo the action of administering the intervention, but the device 
will be programmed such that the vagus nerve is not actually stimulated.
6.6
Procedures Performed to Lessen Probability or Magnitude of Risks:
Psychological Assessments: There is a risk that patients 
may become more upset as a result of being administered 
questionnaires or assessments. If this occurs they will be 
assessed by the research coordinator and if needed Dr 
Bremner or one of the other study psychiatrists on the 
protocol. If deemed clinically appropriate they will be 
assessed with the Sheehan Suicidality Scale and if there is 
a score greater than 0 escorted to the Emergency Room 
for further evaluation
Intravenous Catheters and Venipuncture: Placement of an 
intravenous catheter can result in infection, bruising of the 
skin, or a blood clot in the vein. The risk of these 
complications occurring will be reduced by having the 
procedures performed by a professional under clean 
conditions and using sterile procedures. Dizziness and 
fainting are rare risks of blood draws that will be reduced 
by having the subject supine. There are no long-term side 
effects. 
Vagal Nerve Stimulation: Stimulation of the vagus nerve 
may cause muscle twitching, discomfort, or pain during 
treatment. Hoarseness, a change in voice, or change in 
taste are other temporary possible consequences but 


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these resolve when treatment is stopped. These risks will 
be minimized by stopping the procedure or reducing the 
intensity of the stimulation
H2[15O] and PET: H2[15O] or radiolabeled water has been 
administered to thousands of subjects without side effects 
or toxicity to date at the doses to be used in this study. Dr 
Bremner holds an IND for use of radiolabeled water at 
Emory University. H2[15O] is a radioactive materials. Each 
patient will have eight H2[15O] blood flow scans. For each 
O-15 water scan 20 mCi of H2[15O] will be injected as an 
intravenous bolus. The body organs which receive the 
highest dose of H2[15O] is the intestine and gonads. The 
radiation dose to body organs in this study is well within 
the Food and Drug Administration (FDA) national 
guidelines for radiation exposure for human research 
studies and less than the total amount that is permitted 
for research studies in one year. Risk will be reduced by 
careful screening. The subjects will be asked if they have 
participated in research studies that involved radiation 
over the past year. Risks are reduced by the principles of 
ALARA, or As Low As Reasonably Allowable, which involves 
time (reducing time exposure), distance (keeping dose 
away from subject) and shielding (using lead shields to 
protect from radiation as much as possible). Risk will also 
be reduced by ensuring radiation administration is not 
greater than that outlined in the protocol, and which is 
below limits for a single session set by regulatory agencies, 
and that subjects do not participate in more than three 
research sessions with radiation in a 12 month period, also 
per guidelines. Also, they will be advised that they should 
not participate in other research studies involving 
radioactivity over the next year without consulting Dr. 
Bremner first. There is a small risk of claustrophobia with 
PET. If needed the study will be stopped. 
MRI: Subjects can become claustrophobic in the scanner. If 
needed the study can be stopped or 1-2 mg lorazepam 
given by mouth. If there is indwelling metal in the head 
this can cause injury. Subjects will be screened for 
indwelling metal.
Opioid Use Related Videos: Viewing videos about opioid 
use may result in an increase in opioid craving. Viewing 
videos on smart glasses may cause wooziness or motion 
sickness. The research staff will debrief subjects, which 
involves talking about the experiences and helping 


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subjects to process whatever emotions come up for the 
subject. If needed, for example if the subject is 
experiencing suicidal thoughts, further action will be taken 
if necessary as outlined above. Risks will also be reduced 
by having the research coordinator talk about their 
thoughts and feelings and craving after exposure to the 
drug use video. 
Procedure for Protecting Against Potential Risks: 
Supervision: All of the scans will be done in the presence 
of constant supervision with experienced research staff 
always in attendance and in an institution specifically 
designed, equipped and functioning in support of these 
type studies. In the event that some serious medical 
complications could occur, the PET scan facilities are 
located in Wesley Woods Hospital on the Emory University 
campus and can provide immediate care. Confidentiality:  
All of the information obtained from patients is quoted by 
number and kept locked in confidential files. This 
information is available to study investigators. Risk-Benefit 
Ratio: The risks of participation in this study are small. 
These are outweighed by the potential benefit which a 
better understanding of the effects of OUDs could have for 
society.


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Adverse events (AEs) are evaluated at each visit and 
reported to IRB using standard Emory IRB reporting 
guidelines. Serious adverse events (SAEs) (as defined by 
CRF 312.32) are reported to the IRB using standard Emory 
IRB reporting guidelines. All AE and SAE reports will 
include a description of the event, severity, relationship to 
the study medication or procedures, any intervention 
required, and date of the resolution of the event (or 
otherwise listed as ongoing). SAEs include any fatal event, 
immediately life threatening event, permanently or 
significantly disabling event, event requiring prolonged 
inpatient hospitalization, or any congenital anomaly, and 
any other event that deems to result in a significant 
hazard, contraindication, side effect or precaution. 
Written IND safety reports will be submitted to the FDA by the IND 
sponsor, for serious, unexpected suspected adverse reactions 
within 15 calendar days of learning of its occurrence. If the event is 
fatal or is deemed to be life threatening, the report will be made 
within 7 calendar days.  The IND sponsor will also make an 
assessment of whether the event constitutes an unanticipated 
problem posing risks to subjects or others (UP). This assessment will 
 
Figure 4. UG3 Brain Imaging Study Protocol. Patients receive two minute VNS or sham stimulation at 
onset of opioid cue videos and with no stimulus. Blood is drawn at the time points bounded by purple 
box. O-15 functional scans show red/yellow activity in cortex.


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be provided to the Emory University IRB, which, in turn will make a 
final determination.  If the Emory IRB determines an event is a UP it 
will notify the appropriate regulatory agencies and institutional 
officials.
All non-compliance/unanticipated problems, serious 
adverse events, audits and investigation reports will be 
reported to the Emory IRB following the standard 
reporting obligations.
NVNS devices are provided by ElectroCore Inc, are FDA 
approved for the treatment of headache, and currently 
approved by the Emory IRB for the study of PTSD with 
demonstrated safety and efficacy.
Included are all surveys and questionnaires. Data stored 
include information from surveys and questionnaires and 
all data are stored in the Emory Redcap system. 


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6.7
Data Collected and Method of Attainment: Data is collected with surveys 
and questionnaires and stored securely in the Emory Redcap system. Other 
data collected include blood for measurement of biomarkers, brain imaging 
data and wearable sensing device (autonomic function) data. Data is kept 
on secured Emory servers and under double lock and key in EP12 Emory 
Clinic Psychiatry and the CSI. 
7.0
Data and Specimen Banking* N/A ☐
7.1
Data or specimens will not be banked for future use.
7.2
Data will not be stored or associated with each specimen for future 
use.
7.3
Data or specimens will not be released for future use.
8.0
Sharing of Results with Participants*
8.1
There are no plans to share results with study participants. If we 
find something of urgent medical importance, then we would like to 
be able to share it with the participant. This will be a very rare 
occurrence. 
8.2
If the researchers are concerned about something they see on the 
scan they will tell the participant, and ask them if they want the 
 
Figure 2.The UG3 phase involves an initial dose finding and parameter verification phase with iterative modeling and machine 
learning to refine the protocol in an exploratory open label basis in 20 patients with recently treated OUDs, followed by a second 
group of similar OUD patients randomized to nVNS or sham with assessment of physiologic, inflammatory, behavioral and brain 
response to drug cues (videos). Go/No Go criteria determines movement to UH3 phase. 


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scan to be reviewed for healthcare purposes (possibly by other 
clinicians). They may then be referred for medical treatment.  The 
participant and/or their insurance company may have to pay for the 
review for healthcare purposes, and for any such treatment.
9.0
Study Timelines*
9.1
Describe:

The duration of an individual participant’s participation in the 
study will be up to 3 study visits. We may also call them 
around 6 weeks after the visits to repeat a few questionnaires 
(Addiction Severity Index, SHAPS-C, COWS, NRS Pain Scale, the 
Subjective Units of Distress Scale, and the Visual Analogue 
Scale (VAS)) and see how they are doing. If they took a VNS 
device home then we will ask them about usage and remind 
them to return this to the study team.

We expect to enroll all study participants within 2 years. 

The estimated date for the investigators to complete this 
study is 3/31/2025 but this depends on whether they are 
allowed to continue to the UH3 phase. This protocol contains 
details about the UG3 phase.
10.0
Inclusion and Exclusion Criteria*
10.1 Inclusion and exclusion criteria are listed below. Potential 
participants will be screened for eligibility by a staff member. We 
will try to pre-screen subjects via phone using a verbal consent and 
a waiver of documentation when possible. Otherwise, potential 
subjects will come in for a screening visit. At the first visit, study 
staff will confirm eligibility using a checklist.
10.2 The Inclusion and Exclusion Criteria for Study #1: Subjects aged 18 
and over who: 1) meet criteria for OUDs based on DSM-5 criteria. 
The Inclusion and Exclusion Criteria for Study #2: Subjects aged 18 
and over who: 1) meet criteria for OUDs based on DSM-5 criteria; 2) 
have IV access.
Exclusion Criteria: 1) positive pregnancy test; 2) meningitis; 3) 
moderate traumatic brain injury; 4) neurological disorder or organic 
mental disorder; 5) history of loss of consciousness greater than 
one minute; 6) current pregnancy or breastfeeding for women; 7) 
current or lifetime history of schizophrenia, based on the SCID; 8) a 
history of serious medical or neurological illness, such as 
cardiovascular, gastrointestinal, hepatic, renal, neurologic or other 
systemic illness; 9) evidence of a major medical or neurological 
illness that is based on the clinical judgment of the study 
psychiatrist; 10) carotid atherosclerosis; 11) cervical vagotomy. 


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Several of the above exclusions will be based on the clinical 
judgment of the study physician. If reviewed and deemed 
acceptable by the study physician some exclusions may not 
preclude participation.
10.3 The following populations will also be excluded from the research: 

Adults unable to consent

Individuals who are not yet adults (infants, children, 
teenagers)

Pregnant women

Prisoners
11.0
Vulnerable Populations* N/A ☒
12.0
Local Number of Participants
12.1 Study #1 will be to optimize dosing (N=20) and Study #2 to measure 
brain and biological correlates of nVNS versus sham in conjunction 
with exposure to drug use cues (N=20). 
12.2 We will ask IRB to approve 60 enrollees (total) in order to account 
for some screen failures. We would like to have 20 in each study to 
complete research procedures.
13.0
Recruitment Methods
13.1 Subjects will be recruited from newspaper advertisements, 
websites (like Nextdoor) and/or fliers. We may also recruit from the 
general outpatient population at Emory and the data warehouse. 
Providers may also refer patients for the study. Participants in 
previous research studies who have opted in for future contact 
might also be invited. Once a potential subject is identified, a staff 
member will schedule a screening interview with them to ensure 
eligibility with study enrollment criteria. If done via phone, a verbal 
consent will be obtained by the study staff member. If eligible, 
subject will sign study consent at first visit before starting any 
research related procedures. If screening is not able to be done via 
phone then screening for eligibility will be done in-person.
13.2 Fliers will be used describing the study inclusion criteria and a few 
of the procedures. 
13.3 For study 1:
Compensation ranges from $75 to a total of up to $250 for the 
study. We will also pay for parking, if needed, at each clinical visit.
Visit 2: $175 ($75 for the MRI and $100 for the visit) 
If subjects are given a VNS device to take home, they will get an 


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additional $75 upon successful return of the device using a prepaid 
return mailer.
For study 2:
Compensation ranges from $75 to a total of up to $350 for the 
study.  We will also pay for parking, if needed, at each clinical visit. 
If used as a backup participant: $50 to cover time and 
transportation costs
Visit 2: $150 (PET Day)
Visit 3: $75 (MRI Day) 
If subjects are given a VNS device to take home, they will get an 
additional $75 upon successful return of the device using a prepaid 
return mailer.
Subjects could potentially participate in both studies. 
A check will be mailed to the participant after participation is 
completed. Sometimes this can take 3-4 weeks for Emory to 
approve and cut the check. Another method of payment that will be 
offered is using the Greenphire ClinCard system.
14.0
Withdrawal of Participants*
14.1 The PI does not anticipate any circumstances where a participant 
may wish to withdraw since this study only requires a very short-
term in-person participation. However, if after data collection, a 
participant contacts the PI wishing to not be included in any data 
analysis/publication, their data will be withdrawn from analysis 
when possible.
14.2 If the investigator decides to terminate a subject’s participation in 
the research, the investigator will explain to the subject the reasons 
for this action and, as appropriate, other options for this 
participant. 
14.3 As soon as a participant informs the PI they wish to withdraw, a 
notation will be made in the subject’s binder and/or in Redcap. This 
documentation will include the date, rationale, and what 
components of the study for which the subject chooses to continue 
participation. 
15.0
Risks to Participants*
15.1
List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the participants related the participants’ participation 
in the research.


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Psychological questionnaires/interview: Being asked 
questions about the stress in your life or your mood and 
opioid use may cause you to have unpleasant and/or 
upsetting feelings or have an increase in opioid craving.  If 
this happens, then you can take a break from the 
interviews.  You can also slow down and take longer to do 
the tests. Should you so desire, a counseling session 
and/or referral for counseling will be made available.
Physiological monitors: (Biopac, Glove, EDA, PPG, SCG, 
etc.) These monitors require you to have sensors attached 
to your skin which may represent an inconvenience to you 
e.g. when adhesives are removed. They may also cause 
mild skin irritation or itching. The glove cold application 
may cause temporary numbness, which stops after 
application. The hot application may cause temporary 
redness/skin sensitivity. The subject may feel itchiness due 
to sensor hookups on hands (due to sticky electrodes and 
gels) and temporary numbness of the arm is possible, 
since the subject will remain in the same position for half 
an hour. The EDA requires you to wear a bracelet-type 
device during (and possibly after) the visit, which may 
represent an inconvenience to you.
Intravenous (IV) catheter and blood draw.  The IV can 
result in infection, bruising of the skin, or a blood clot in 
the vein.  These complications are not common when the 
catheter is inserted by a professional under clean 
conditions.  Dizziness and fainting are rare risks of blood 
draws. There are no long-term side effects. The subject 
may have some discomfort from the blood drawing.  The 
risk from blood drawing is minimal, but may include 
bruising and infection.  The use of sterile precautions will 
decrease the risk of infection.  However, the subject may 
develop a bruise at the site of the puncture, but this is 
expected go away in two to three days.
PET scan:  This research study involves exposure to 
radiation from a Positron Emission tomography (PET) scan.  
This PET scan procedure is routinely used for medical 
purposes; however, radioactive water is investigational 
and not approved by the FDA. This radiation dose is not 
necessary for a subject’s medical care and will occur only 
as a result of the subject’s participation in this study. If a 
subject has had any significant exposure to radiation over 


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the past year or plans to participate in other research 
studies involving radioactivity over the next year, he/she 
should consult with the study team and Dr. Bremner first. 
Some people experience anxiety from the PET scan 
procedure.  Viewing videos on smart glasses may cause 
wooziness or motion sickness. A nurse or technologist will 
be with the subject during the PET scan procedure. If a 
subject becomes claustrophobic, anxious or agitated in the 
PET scanner, the scan will be stopped.  If a subject is not 
able to complete the first PET scan, he/she may not be 
able to continue in the study.  This study will expose 
subjects to a small amount of radiation.  The radiation 
dose that subjects will receive is equal to or less than the 
annual radiation exposure limit allowed for persons who 
are occupationally exposed to radiation (x-ray technicians, 
radiologist). The principal risk associated with a radiation 
does is the possibility of developing a radiation-induced 
cancer later in life. The risk for radiation-induced cancer 
from this study is minimal. Although the risk from 
radiation is cumulative it is not expected to adversely 
affect a subject’s condition or treatment. The risk from 
radiation exposure of this magnitude is considered to be 
comparable to other everyday risks. 
MRI scan: There is the risk that if subjects have indwelling 
metallic foreign bodies in the head that MRI scanning may 
cause local tissue damage. All subjects will be screened for 
indwelling foreign bodies and individuals with indwelling 
bodies will be excluded. Some individuals may feel anxiety 
while in the scanner. If needed, the study will be stopped. 
There are no other risks of MRI scanning.
Subjects will be getting a scans (PET/MRI) for research 
purposes only.  The research does not require the scans to 
be read for healthcare purposes. However, if the 
researchers are concerned about something they see on 
the scans they will tell the subject, and ask if he/she wants 
the scans to be reviewed for healthcare purposes (possibly 
by other clinicians), and he/she may then be referred for 
medical treatment.
Opioid Use Related Videos. The viewing of opioid use 
related videos may cause some anxiety or feelings of 
craving for opioids. Subjects are able to stop this test at 


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any time if they experience anxiety, excessive cravings, or 
other problems or are uncomfortable with the procedure.
VNS Testing. Sometimes, a subject may experience 
hoarseness, shortness of breath, throat pain, cough, 
abdominal pain, headache, and/or change in voice during 
treatment. A tingling/pricking/twitching feeling where the 
device is applied is normal, but should not cause major 
discomfort. These effects usually stop right away once the 
treatment is completed. Mild skin irritation or dizziness 
are other possible side effects. The VNS device should not 
be used on patients who have any of the following 
conditions: an active implantable medical device, such as a 
pacemaker, defibrillator, cochlear implant, and other 
implanted electronic device; a history of significant carotid 
atherosclerosis; or a cervical vagotomy.
Reproductive Risks. Since this research may have bad 
effects on a fetus and should not be done during 
pregnancy, it is necessary that a pregnancy test be done 
first, even if, to the best of the subject’s knowledge, they 
are not pregnant now.  Women of childbearing potential 
will take a urine pregnancy test when they arrive for their 
visits.  If the test is positive they will not be able to 
participate in the study.  This study may be hazardous to a 
breast-feeding child.  Breast feeding mothers may not 
participate in this study.
Women who may be pregnant should not be in this study 
because of possible effects of radiation exposure on their 
unborn child.  Both men who may later father children and 
women of childbearing potential should be aware that 
exposure to radiation poses a very slight risk of genetic 
mutation in the next generation.
Fasting. In order to undergo study testing, subjects need to 
be fasting before their study visit for the scan day until the 
scans are completed. Some people may show discomfort 
from this prolonged fasting, although true hypoglycemia is 
rare. A sweetened beverage will be administered if 
patients complain of lightheadedness or other fasting-
related symptoms.
15.2 The long-term effects of the chronic use of VNS have not been 
evaluated. 


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15.3 The PET scans and VNS testing may have risks to an embryo or fetus 
should the subject be or become pregnant.
16.0
Potential Benefits to Participants*
16.1 This study is not designed to directly benefit participants. 
17.0
Data Management* and Confidentiality
17.1
We will use analysis of variance models with change in blood flow 
as dependent variable and absolute blood flow during control task as well 
as study group as explanatory variables. This analysis will assess 
differences in brain function according to diagnosis correcting for 
potential differences in baseline (control task) values. The ANOVA model 
will be blocked by the matching factor of past alcohol exposure. Analyses 
will be adjusted for whole brain blood flow. Additional control factors, 
including patients’ age, age of onset of traumatization, years of 
education, IQ, OUD symptom level and duration of disease, use of oral 
contraceptive birth control, and smoking, will be entered in the model if 
they are significantly different between the study groups at an alpha level 
of 0.25, and/or if they are found to be confounders in the analysis, i.e., if 
they cause a change of >10% in the parameter estimate for study group 
when entered in the model. Adjusted means of blood flow will be 
computed for each combination of group and task to better describe the 
results. Point estimates and confidence intervals for the difference 
between groups will be assessed before and after including the 
covariables mentioned above in the model. Additional analyses will 
compare OUD patients with and without a history of co-morbid 
depression. 
In all these analyses linear model assumptions, adequacy of fit, and 
presence of outliers will be checked by inspecting residual plots and 
influence statistics. Collinearity for variables included in the model will 
also be checked. Appropriate remedies will be applied, if necessary, to 
improve model fit and minimize collinearity.
Additional exploratory analyses will use subtraction analysis techniques 
to look for additional areas of activation for the purpose of generating 
hypotheses for future studies. Images of absolute blood flow will be 
subjected to a subtraction type analysis. Images will be realigned to the 
first image in the series and warped into a common anatomical space 
using methods described in the preliminary results. Images will be then 
analyzed using the general linear model of Friston for statistical analysis. 
The mean of blood flow scans within condition will be calculated and 
comparisons performed between conditions to assess blood flow with 
the condition. Areas of increased and decreased blood flow within 
patient group will be examined, as well as the interaction between 


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condition and diagnostic group. Images of t statistic will be created and 
surveyed for hypothesized regions (i.e. medial prefrontal cortex) where 
uncorrected z score values are greater than 2.86 (corresponding to a 
corrected p value of > 0.005).
Calculation of Sample Size 
For calculation of sample size needed for PET measurement of anterior 
cingulate activation, we used values for blood flow in the amygdala 
(scaled to whole brain blood flow) based on previous pilot data. Fear-
related tasks resulted in a 6.9 + 4.8% increase in amygdala blood flow 
versus 1.2 + 1.4% in controls (effect size 1.39). With two tails, an alpha 
value set at 0.05 and a power of 0.80, 10 subjects are needed in each 
group (VNS v sham) to show a significant difference between patients 
and controls (i.e. group by condition interaction). The number of subjects 
in each group will therefore be adequate to answer the questions 
proposed in this study. 
17.2 All study staff will take required training prior to working with 
participants and/or PHI. All data will be kept in either locked offices 
in secure buildings or online via Redcap or on a password restricted 
research server. A certificate of confidentiality will be in place.  
Confidentiality will be assured by the use of subject codes when 
possible rather than personal identifiers. After the study is 
completed, the study database will be secured, and information will 
only be entered using subject identifier codes rather than personal 
identifiers.  Published results will be presented as group data, 
without identifiers.
17.3 A (bi) weekly meeting with the staff, Study Coordinator and the PI is 
held to discuss any issues that may arise. A review of data is done 
for accuracy and protocol compliance. Data collection forms are 
verified for accuracy before storing in database. Describe any 
procedures that will be used for quality control of collected data.
17.4 Describe how data or specimens will be handled study-wide:

Study ID, date of visit, and type of sample will be included for 
each specimen

Specimens will be stored in a -80 freezer at EP12 or RSPH 

Specimens will be stored until they are fully utilized for testing 

The Pearce Lab and the study team will have access to the 
data and/or specimens

The Pearce Lab uses a spreadsheet system to inventory what 
has been brought to their lab for testing. A study team 
member will deliver the samples and the lab will sign off on 


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the delivery. The data will be sent from Dr. Pearce to the PI 
and/or study staff for saving to the research server. 

Specimens will be transported via dry ice using coolers from 
Wesley Woods and/or EP12 to the Pearce Lab in RSPH.
18.0
Provisions to Monitor the Data to Ensure the Safety of Participants*
18.1 Describe:

The Data Safety Monitoring Plan (DSMP) outlined below will adhere to 
the protocol approved by the institutional IRB responsible for study 
oversight. An IRB-approved written informed consent will be obtained 
from each subject at entry into the study; elements of informed consent 
will include:  (a) having the subject review the study consent form; (b) 
having the investigator(s) or study staff meet with the subject to review 
the consent, confirm understanding, and answer any questions; and (c) 
once the investigator(s) or study staff are convinced that the protocol is 
understood and that there is agreement to participate, having the 
consent signed.  A copy of the signed consent form will be provided to 
subject. Documentation of the informed consent process will be made in 
the research and/or medical records as appropriate or in Redcap.  The 
principal investigator (PI) or his designated appointee will review data 
collection forms for completeness and accuracy of the data as well as 
protocol compliance on an as needed basis. Any data inconsistencies will 
be resolved by study staff as soon as possible.  The PI will review this 
protocol on a continuing basis for subject safety and protocol deviations 
or study noncompliance.  Reportable Events will be communicated to the 
local institutional IRB as required. Self-monitoring will be completed by 
the study staff every 6 months. All findings/observations related to safety 
will be documented in REDCap and shared with the study team as well as 
independent monitor. Any candidate safety-related adverse events will 
be discussed immediately, and the independent monitor will provide 
recommendations about the next best steps.  
Stopping Rules for Mental Stress Testing.
Absolute Indications for Termination
•
Moderate-to-severe chest pain at a level that the patient 
wishes to stop. 
•
Central nervous system symptoms (eg, ataxia, dizziness, or 
near syncope). 
•
Signs of poor perfusion (cyanosis or pallor). 
•
If the patient becomes excessively anxious or uncomfortable, 
or requests us to stop.
Relative Indications for Termination


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•
Drop in systolic blood pressure >10 mm Hg (persistently below 
baseline) despite an increase in workload, in the absence of 
other evidence of ischemia. 
•
Increasing chest pain. 
•
Fatigue, shortness of breath, or wheezing
•
General appearance (see below). 
•
Hypertensive response (systolic blood pressure >250 mm Hg) 
•
Development of bundle-branch block that cannot be 
distinguished from ventricular tachycardia. 
Stopping Rules for Study
      Absolute indications for study wide termination (determined by the 
PI)
•
the intervention is associated with adverse effects that call 
into question the safety of the intervention
•
difficulty in study recruitment or retention that will 
significantly impact the ability to evaluate the study endpoints 
•
any new information becomes available during the trial that 
necessitates stopping the trial
•
other situations occur that might warrant stopping the trial
Plans for transmission of temporary or permanent suspension actions: Any 
actions that mandate temporary or permanent suspension of study will be 
transmitted to the institutional IRB, and, if appropriate, to the IND sponsor, FDA, 
or the National Institutes of Health.
Plans for protecting subject confidentiality: All information and materials that 
are obtained for research purposes only will be kept in strict confidence.  
Confidentiality will be assured by the use of subject codes when possible rather 
than personal identifiers. After the study is completed, the study database will 
be secured, and information will only be entered using subject identifier codes 
rather than personal identifiers.  
Plans for assuring data accuracy and protocol human safety compliance: An IRB-
approved written informed consent will be obtained from each subject at entry 
into the study; elements of informed consent will include:  (a) having the subject 
review the study consent form; (b) having the investigator(s) or study staff meet 
with the subject to review the consent, confirm understanding, and answer any 
questions; and (c) once the investigator(s) or study staff are convinced that the 
protocol is understood and that there is agreement to participate, having the 
consent signed.  A (bi) weekly meeting with the staff, Study Coordinator and the 
PI is held to discuss any issues that may arise. A review of data is done for 
accuracy and protocol compliance. Data collection forms are verified for 


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accuracy before storing in database. The PI will review this protocol on a 
continuing basis for subject safety. Patient Monitoring: will be performed by the 
PI, the Co-Investigators, and the Research Coordinator(s). Any unanticipated 
events are reported to the IRB in a timely manner per protocol.  
The above detailed plans should assure data accuracy and protocol human safety 
compliance for this study.  These include computerized database management, 
and IRB oversight and communication.  This plan, together with oversight by the 
IRB, should be sufficient for studies that do not require a DSMB.
The Independent Monitor for this study is Dr. Jeanie Park. Dr. Park is not 
associated with this research project and thus works independently of the PI, Dr. 
Bremner. Dr. Park is not a part of the key personnel involved in this grant, and is 
qualified to review the patient safety data generated by this study because of 
her unique expertise in autonomic physiology. Dr. Park’s CV is attached. 
She will review documentation of subject-reported adverse events every 6 
months.
19.0
Provisions to Protect the Privacy Interests of Participants
19.1 Participants will be interviewed in private research room with the 
study staff. A Certificate of Confidentiality is in place since this is 
funded by NIH/NIDA. Sensitive questions will only be asked as 
needed for scientific aims.
19.2 Study staff will strive to limit interactions from people outside of 
the study team. Private areas will be used when possible. The study 
staff will explain study procedures to the participant.  At any time, 
the participant is able to request a break or skip a question if s/he is 
uncomfortable with the question and/or interview. 
19.3 The study team is able to access any information at any time since 
they are protecting all the hardcopy and digital data. No one else 
outside of the study team will be able to access the information.
20.0
Economic Burden to Participants
20.1 Participants will not have any costs, except for basic things like 
transportation, for participating in the research. 
21.0
Consent Process
21.1
Verbal consent may be done for screening purposes to ensure the 
subject is eligible for the study. If not, screening will be done at the first 
in-person visit.
At the first clinic visit, the study staff will begin the visit with the signing 
of the informed consent. After signing the consent form, they will begin 
the study procedures.


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
The consent process will take place at either Wesley Woods, 
EP12, Emory Clinics, or RSPH.

The study will be discussed with the potential participant prior 
to the visit. The study will begin after the consent process. 

The study staff will ensure that the participant continues to 
understand the procedures and will answer any questions that 
come up.

Informed Consent Process:
o
One of the study coordinators will lead the informed 
consent process.
o
The consent discussion will vary but should take around 
15-20 minutes prior to any procedures being done. 
o
Once at the research center, the research coordinator 
will discuss all aspects of the research protocol with the 
subject and go over the consent and any questions they 
may have in regards to the study. After the discussion, 
the research coordinator will ask the subject if they wish 
to participate in this study and both will sign the written 
consent. The subject will be given a copy of the consent 
to keep. The consent clearly states that participation in 
this study is voluntary and they can leave the study at 
any time, for any reason or for no reason. If they 
withdraw they will still keep all health care services that 
they would expect from Emory University and their 
affiliates.
o
Subjects will be asked to restate some of what they have 
heard in order to make sure they are aware of all 
procedures. 
Non-English Speaking Participants N/A ☒
Participants who are not yet adults (infants, children, teenagers) 
N/A ☒
Cognitively Impaired Adults N/A ☒
Adults Unable to Consent N/A ☒
22.0
Process to Document Consent in Writing
22.1 Consent of the subject will be documented in writing in the 
subject’s chart or in Redcap.
23.0
Setting
23.1 Describe the sites or locations where your research team will 
conduct the research.


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
Subjects will be recruited from the clinic, newspaper 
advertisements, online websites, referrals, and/or fliers. 

Research procedures will be performed at Emory Clinics, 
Wesley Woods, and/or Executive Park 12 research rooms.

Local detox or drug treatment centers might be used as sites 
with an IRB approved Site permission letter.
24.0
Resources Available
24.1 Describe the resources available to conduct the research:

Subjects in this study will be patients with opioid use disorders 
based on DSM-5 criteria recruited from the greater Atlanta 
metropolitan area. We will study patients with OUDs on 
medication treatment. According to the Substance Abuse and 
Mental Health Services Administration (SAMHSA), 109,777 
(4.18%) have non-medical use of prescription pain relievers, 
and 48,302 are estimated to have an OUD. Based on this, 
there is an ample population of individuals for the study. 

Recruitments for studies 1 and 2 will take place over two 
years.

Emory is one of the top biomedical research institutions in the 
nation, ranking among the top 20 schools of medicine in NIH 
research funding, at $218 million in 2008. Emory has more 
than 2,500 faculty members. Emory Healthcare, which 
includes Emory’s own or affiliated clinics and hospitals, is the 
largest service provider in Georgia. The clinics and hospitals, 
with almost 3,000 inpatient beds and more than 2 million 
annual outpatient and emergency visits, create an exceptional 
environment for patient-oriented research. Emory physicians 
also provide a major portion of the city’s indigent and public 
health care. It is considered to be the premier institution for 
cardiology and cardiac surgery care in the Southeastern 
United States. Atlanta has also one of the largest African 
American populations of any city in the U.S. and 
approximately 30% of all patients in Emory Healthcare 
hospitals and clinics are African American in origin.

Emory Brain Health Center and Department of Psychiatry. 
The Emory Department of Psychiatry & Behavioral Sciences, 
chaired by Mark Rapaport, M.D., is one of the most exciting 
and rapidly growing psychiatry departments in the U.S. today. 
The faculty of the department actively pursue goals of 
innovation in research, education and delivery of care. Emory 
has moved from being a primarily a clinical and regional 
department to one of the most rapidly expanding psychiatry 
departments in the country. Drs. Rapaport, Bremner, Welsh 


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and Dudley are all clinical psychiatrists in the Emory Clinic 
Psychiatry located at the Emory Brain Health Center in 
Executive Park, Atlanta, Georgia. Drs Welsh and Dudley have 
access to hundreds of patients with opioid use disorders. The 
department now has a number of NIMH-funded investigators, 
and the Psychiatry Department within Woodruff Memorial 
Building (WMB) has basic research laboratories for psychiatry 
faculty. The laboratories include facilities for molecular 
biology, neurochemistry, in vitro autoradiography, and 
psychopharmacology. One of the highlights of working at 
Emory is the lack of boundaries between departments, the 
warm collegiality, and the opportunity to collaborate with 
other scientists in different departments, as well as at Emory 
College, the CDC, and Georgia Tech. A number of our faculty 
have joint appointments and laboratory space as well as active 
collaborations with the Center for Disease Control
(CDC). The CDC is conveniently located on the Emory Campus. 
Highlights of the program include collaborations in Chronic 
Fatigue Syndrome, Psychoimmunology, and Mind-Body 
interactions. The Wesley Woods Hospital has large inpatient 
and outpatient programs in geriatric psychiatry with active 
research programs. Emory Clinic is our outpatient adult 
psychiatry clinic and is an excellent source for research subject 
recruitment. At Grady Hospital, the public hospital which 
serves Fulton and DeKalb counties, there are both inpatient 
and outpatient psychiatric treatment facilities, laboratory 
space, and active research programs. The Emory faculty treat 
the Grady patient population through a foundation program. 
Many of our faculty are located at the Yerkes Regional 
Primate Center and the Center for Behavioral Neuroscience, 
which are described in more detail below. Other programs in 
which Psychiatry faculty collaborate or participate are listed 
below.

The Department of Psychiatry is part of the Emory Brain Health 
Center, located at the newly-built Executive Park site of Emory 
Healthcare. As a part of the Emory Healthcare Network, the 
Center brings together more than 400 researchers and clinicians 
specializing in neurology, psychiatry and behavioral sciences,
neurosurgery, rehabilitation medicine, and sleep medicine to 
more rapidly predict, prevent, treat, and cure devastating 
diseases and disorders of the brain. The Emory Brain Health 
Center holds more than 20 centers and programs including the 
Child and Adolescent Mood Program, Epilepsy Center, Pituitary 


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Center, Stroke Center, Treatment Resistant Depression 
Program, and Veterans Program. The facility has fully equipped
conference rooms, office rooms, and rooms dedicated to 
research subject interview purposes. The Child and Adolescent 
Mood Program (CAMP) is located on the second floor of the 
Emory Brain Health Center. CAMP offers services including 
psychopharmacological evaluations, medication management,
individual therapy, and various psychological testing to children 
and adolescents. As part of CAMP, Emory Adolescent Substance 
Use Treatment Services (EAST), Directed by Justine Welsh, 
M.D., a co-investigator on this project, provides psychiatric and 
behavioral interventions to adolescents and young adults with
substance use disorders. The clinic is equipped with a clinical 
laboratory and ancillary services. The clinical laboratory is 
capable of running various urine analyses and blood sample 
tests. A full-time LCSW certified to provide Adolescent 
Community Reinforcement Approach (A-CRA) therapy is 
available to provide treatment on site. Fidelity for A-CRA will be 
measured by recorded session procedures. Recording devices 
are on site and available to each provider. Limited counseling 
sessions will also be documented to monitor endorsed
medication adherence, medication side effects, assessment of 
withdrawal/cravings and reasons for any dose adjustment in the 
electronic health record. The Department of Psychiatry and 
Behavioral Sciences will provide administrative and computer 
support.
Emory Clinical Neuroscience Research Unit (ECNRU). The 
ECNRU, J. Douglas Bremner, MD, Director, is a research program 
at the Emory Briarcliff campus for the study of the neurobiology 
of PTSD and depression and mechanisms of these disorders in 
heart disease. There is 5,000 square feet of space including 
offices and cubicles for the PI and staff and an image processing 
laboratory.
Pearce Lab: A number of serum biomarker analysis 
instrumentation tools are available to Dr. Brad Pearce in
his molecular neuroimmunology laboratory space. In addition, 
the RSPH supplies a shared equipment facility for Dr. Pearce and 
other PIs on the 4th floor. This facility includes a BioRad 
Chemidoc XRSt gel imaging system, an Applied Biosystems 7500 
Fast Real-Time PCR System, Biotek Epoch plate reader with 200 
nm to 999 nm wavelength range and 6- to 384- microplate 
reading capability, and BLX405 plate washer, Sorvall RC64 
centrifuge, Eppendorf 5810R bench-top centrifuge, a Perkin 
Elmer Victor3 1420 fluorescence and luminescence multilabel 


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plate reader, and a Beckman Optima L Series Ultracentrifuge. In 
addition, Dr. Pearce routinely uses the Emory University Flow 
Cytometry Core Facility for his immunology work. This facility
includes the BD FACSort two-laser, four-color benchtop 
analyzer. In addition, the Emory Multiplexed Immunoassay Core 
provides Dr. Pearce and other Emory researchers with use of 
equipment (SECTOR Imager 2400), training and expertise for the 
Meso Scale Discovery Platform. This immunoassay platform 
uses electrochemiluminescence (ECL) detection based on 
ruthenium(II)-tris-bipyridine derivatives. The sensitivity
and dynamic range of the platform is better than most ELISAs 
and has shown fewer matrix effects than ctytobead systems. We 
routinely use this multiplex assay platform for other studies.

Emory Center for Systems Imaging (CSI). The neuroimaging facilities at 
Emory include three research dedicated, Siemens 3T Prisma and Trio 
scanners. All of the functional magnetic resonance imaging (fMRI) 
facilities are equipped with conventional 12-channel head coils, 32-
channel head coils, and new 64-channel head coils that allow for state of 
the art, high temporal and spatial resolution, functional MRI. In 
particular,
these systems are equipped with 32 channels, which can be configured in 
a wide variety of combinations through the TIM software. It includes 
standard sequences for EPI BOLD, diffusion, perfusion imaging, and 
Diffusion Tensor Imaging (DTI). We will have a variety of coils, including a 
32-channel head coil, 12-channel head coil, transmit/receive birdcage 
head coil, flex coils, neck matrix and spine matrix coils. The neuroimaging
community at Emory is comprised of the Biomedical Information 
Technology Center (BITC), Center for Systems Imaging (CSI), and the 
Facility for Education and Research in Neuroscience (FERN). Each of these 
centers are fully staffed with expert MRI physicists, MRI technicians, and 
cognitive neuroscientists. All of these
centers feature (a) MRI simulator ("mock scanner"), to acclimate 
participants to the imaging environment and train them to remain still 
(critically important for pediatric and special populations); (b) full 
psychophysiology recording suite (Biopac: heart rate, startle, skin 
conductance); (c) Eye-Link MRI compatible eye tracker; (d) behavioral 
testing space; and (e) computer room, for data processing and analysis. 
The major imaging equipment housed at CSI includes a 
cyclotron/Radiochemistry lab, a 3T MRI system, a High Resolution 
Research Tomograph (HRRT, CTI Corp.) human brain High Resolution 
Positron Emission Tomography (HRPET) system, an Inveon micro Positron 
Emission Tomography-Computed Tomography (PET-CT) system, and a 
multispectral fluorescence animal imaging system. The Wesley Woods 


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Medical Center has a brain dedicated High Resolution Research 
Tomograph (HRRT) obtained with a National Center for Research 
Resources (NCRR) and Georgia Research Alliance (GRA) grant to Dr. Doug 
Bremner. Other facilities include an on site cyclotron and radiochemistry 
facilities including hot cells and robotic arms as well as a high resolution 
3T MRI.

The Center for Systems Imaging (CSI) Radiochemistry Lab This resource 
is directed by Dr. Mark Goodman and is located on the 2nd floor of the 
Wesley Woods Health Center. It houses a Siemens RDS 111 multiport, 
self-shielded, automated cyclotron producing a 11 MeV, 50 μA proton 
beam. The cyclotron is equipped with targets for the routine production 
of curie amounts of [18F]fluoride, [18F]fluorine, [11C]carbon dioxide, and 
[15O]oxygen. The radiochemistry area is a 2,100 square foot cyclotron 
vault and laboratory which includes:
• four master slave manipulator arm-equipped hot cells
• five mini-cells
• one Siemens computer programmable two reaction vessel 
radiochemical processing unit
• one GE TracerLab FXN unit
• one semi-automated remote mini-syringe pump
• two reaction vessel radiochemical processing units
• one semi-automated remote mini-syringe pump fluorine-18 F2 
radiochemical processing unit
• one automated oxygen-15 water synthesis module
• one GE PETtrace carbon-11 methyl iodide module
• one clean room , hot and cold waste systems and ventilation 
chemical and radiation monitoring
systems.
The radiochemistry laboratory is equipped with four pneumatic tube 
systems located in the four hot cells for rapid delivery of 
radiopharmaceuticals. It also has a variety of modern analytical 
instruments which include 
• one Carroll and Ramsey Associates eleven probe radiation 
detection system
• one Waters Alliance radio-HPLC unit that is configured with 
UV/Vis and IN/US Radiometric detectors and one Waters radio-
HPLC unit that is configured with UV/Vis and Bioscan Radiometric 
detectors
• one Raytest radioactivity thin-layer chromatography system
• two electrically activated rheodyne HPLC injectors
• eight manual rheodyne HPLC injectors and 4 Waters' 515 HPLC 
pumps
• one Bioscan hot cell radiometric detector


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• one Agilent 6890N radio-gas chromatograph equipped with a 
thermal conductivity and flame ionization detectors
• one Oxford sodium iodide detector and well 
counter/multichannel analyzer
• two Capintec 712M dose calibrators with four remote ionization 
chambers and four remote readouts and four Mettler electronic 
balances.
Here is a list of tracers currently produced:
2-FDG (PETNET) Human
C-11 HOMADAM (WW-CSI & Yerkes#) Human
N-13 NH3 (PETNET) Human
F-18 FECNT (WW-CSI & Yerkes#) Human
C-11 PIB (WW-CSI & Yerkes#) Human
F-18 FACBC (WW-CSI & Yerkes#) Human
C-11 Flumanezil (WW-CSI & Yerkes#) Human
F-18 FACPC (WW-CSI & Yerkes#) Human
C-11 Raclopride (WW-CSI & Yerkes#) Human
F-18 FEmZIENT* (WW-CSI & Yerkes#) Animal
O-15 Water (WW-CSI) Human
F-18 FEpZIENT* (WW-CSI & Yerkes#) Animal
O-15 Oxygen (WW-CSI) Human
C-11 MENET* (WW-CSI & Yerkes#) Animal
F-18 Fallypride (WW-CSI & Yerkes#) Animal
Cu-64 ligands (WW-CSI & Yerkes#) Animal
F-18 WAY (WW-CSI & Yerkes#) Animal
C-11 MDL (WW-CSI & Yerkes#) Animal
C-11 WAY (WW-CSI & Yerkes#) Animal
F-18 FMISO (WW-CSI & Yerkes#) Animal
*eIND in progress for first in humans
#Yerkes only animals

Georgia Tech/Emory Department of Biomedical Engineering In 
September 1997, after an intense planning and review process that 
involved faculty from both institutions, Georgia Tech joined with Emory 
University School of Medicine to establish the Georgia Tech/Emory 
Department of Biomedical Engineering (BME) (Michael Thomas, PhD, 
Acting Chairman). This new academic unit is a unique partnership 
between a public and a private institution. Dr. Clifford is a faculty 
member in this department. This Department represents the strong 
commitment that both Emory and Georgia Tech have toward enhancing 
research in the biomedical and bioengineering sciences, and will 
significantly enhance research and education opportunities in these 
areas. State-of-the-art facilities are available at Georgia Tech, including 
the new biocomplex building to be completed in the future. Georgia Tech 


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is located just west of downtown Atlanta, about 15 minutes from the 
Emory campus.

The Inan Research Group is housed in the Technology Square Research 
Building (TSRB), one of eleven buildings on the campus that houses 
Electrical and Computer Engineering (ECE) faculty. The Inan Research 
Group has its own lab space in TSRB, with state-of-the-art test 
instruments including oscilloscopes, function generators, power supplies, 
multimeters, and signal analyzers. The lab is also well-equipped for rapid
electromechanical prototyping (e.g., soldering stations, hand tools), 
physiological monitoring, and data acquisition, and includes computers, 
microcontroller and sensor evaluation boards, and all other necessary 
tools for prototyping and evaluating the proposed hardware. For data 
analysis and visualization, in addition to the computers in the lab, there is 
a separate student carrel space with computers equipped with necessary 
specialized software tools (e.g., MATLAB, SolidWorks).

Neural Engineering Group, City University of New York
The Neural Engineering Group at The City College of New York, directed 
by Marom Bikson, Ph.D., analyzes nervous system function at multiple 
scales spanning sub-cellular, single cell, tissue, animal, to human 
cognitive levels. Similarly, our translational research and development 
program integrates experimental testing, medical device development, 
and clinical trials – with the over-arching goal of improving human health 
through engineering innovation.

There is a risk that patients may become more upset as a result of 
being administered questionnaires or assessments. If this occurs 
they will be assessed by the research coordinator and if needed 
Dr. Bremner or one of the other study psychiatrists on the 
protocol (Drs. Welsh, Dudley).

Viewing videos about opioid use may result in an increase in 
opioid craving. The research staff will debrief subjects, which 
involves talking about the experiences and helping subjects to 
process whatever emotions come up for the subject. If needed, 
for example if the subject is experiencing suicidal thoughts, 
further action will be taken if necessary. For example, if subjects 
are suicidal they will be escorted to the Emergency Room, and 
they will be instructed that if they have problems with feeling 
upset they should call one of the clinicians and if they develop 
active suicidal ideation with a plan they should go to the 
Emergency Room.

A (bi) weekly meeting with the staff, Study Coordinator and the PI 
will be held to discuss any issues that may arise and to ensure that 
all persons assisting with the research are adequately informed 


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about the protocol, the research procedures, and their duties and 
functions.
25.0
Multi-Site Research when Emory is the Lead Site*N/A ☒ 
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Owen AM, McMillan KM, Laird AR, Bullmore E. N-back working memory 
paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain 
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Gray JR, Chabris CF, Braver TS. Neural mechanisms of general fluid 
intelligence. Nat Neurosci. 2003;6(3):316-322.
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Newcomer JW, Craft S, Hershey T, Askins K, Bardgett ME. Glucocorticoid-
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Schmand M, Weinhard K, Casey ME, Eriksson L, Jones WF, Reed JH, Treffert J, 
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Richerzhagen N, Flugge G, Heiss WD, Nutt R. Performance evaluation of a new LSO 
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Weinhard K, Schmand M, Casey ME, Baker K, Bao J, Eriksson L, Jones WF, 
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Vollmar S, Young JW, Heiss WD, Nutt R. The ECAT HRRT: Performance and first 
clinical application of the new high resolution research tomograph. IEEE Trans Med 
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Mickey RM, Greenland S. A study of the impact of confounder selection criteria 
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Friston K. Statistical parametric mapping. In: Thatcher R, Hallett M, Zeffiro T, 
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the assessment of significant change. J Cereb Blood Flow Metab. 1991;11:690-699.

ICF_000.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Non-invasive Vagal Nerve Stimulation in Opioid Used Disorders 
 
 
NCT04556552 
 
 
Date: 07/18/2022  
 
 
 
 


 
 
Page 1 of 13 
 
Version Date: 7/18/2022 
IRB Form 06162020 
  
You Are Being Asked to Be in a Research Study 
Concise presentation of key concepts 
 
You are being asked to be in a research study. A research study is designed to answer a 
scientific question. If you agree to be in the study you will be one of 20 people who are being 
studied, at Emory and elsewhere.  
 
Why is this study being done?  
This study is being done to answer the question: what are the effects of Vagal Nerve 
Stimulation (VNS) on behavior as well as blood and brain responses to craving in patients with 
OUDs? You are being asked to be in this research study because you have been diagnosed with 
an OUD.   
 
Do you have to be in the study?  
It is your decision to be part of this research study. You do not have to be in it. Your choice will 
not affect your access to medical care for your condition. Before you make your decision, you 
should take time to learn about the study. 
 
What do I have to do if I choose to participate in this study? 
If you are eligible and want to be part of the study, you will participate for 2 or 3 study visits 
and a follow up call around 6 weeks after your visits.  The researchers will ask you to do the 
following: complete several psychiatric questionnaires/interviews, blood draws, physiological 
monitoring with several devices (explained below), VNS testing, and brain imaging. ALL of 
these procedures will be paid for by the study.    
 
How is this study going to help you?  
If you are in the study, you will be helping the researchers answer the study question.  
 
What are the risks or discomforts I should know about before making a decision?   
The study will take time. The drug/device/procedure that is being tested may not work any 
better than regular care, and may even cause harm. All studies have some risks.  Some risks 
are relatively small, like being bored or losing time.  Some are more serious – for this study, 
these include an increase in opioid craving, anxiety during scans, skin irritation, 
tingling/pricking/twitching feeling where the VNS device is applied, radiation exposure, loss of 
privacy, and breach of confidentiality.  A full list of expected risks, their frequency and severity 
are in the “What are the possible risks and discomforts?” section of this document. 
 
 


 
 
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Alternatives to Joining This Study 
Since this is not a treatment study, the alternative is not to participate. 
 
Costs 
You WILL NOT have to pay for any of the study procedures.   
 
What Should I Do Next? 
Read this form, or have it read to you.  Make sure the study doctor or study staff explains the 
study to you. Ask questions (e.g., about exact time commitment, about unfamiliar words, 
more details on specific procedures, etc.) Make sure you understand.  Take time to consider 
this, and talk about it with your family and friends. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Emory University 


 
 
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Version Date: 7/18/2022 
IRB Form 06162020 
Emory University 
Consent to be a Research Subject / HIPAA Authorization  
 
Title:  Non-invasive Vagal Nerve Stimulation in Opioid Used Disorders – Study 2 
 
Principal Investigator: J Douglas Bremner, MD 
 
 
Sponsor-Investigator: J Douglas Bremner, MD 
 
 
Study Supporter: National Institute on Drug Abuse (NIDA) 
 
Introduction 
You are being asked to be in a medical research study. This form is designed to tell you everything you need to think 
about before you decide if you want to be a part of the study.  It is entirely your choice.  If you decide to take part, you 
can change your mind later on and withdraw from the research study. The decision to join or not join the research 
study will not cause you to lose any medical benefits.  If you decide not to take part in this study, your doctor will 
continue to treat you. 
 
Before making your decision: 
• 
Please carefully read this form or have it read to you 
• 
Please listen to the study doctor or study staff explain the study to you  
• 
Please ask questions about anything that is not clear 
 
You can take a copy of this consent form, to keep. Feel free to take your time thinking about whether you would like to 
participate. You may wish to discuss your decision with family or friends. Do not sign this consent form unless you have 
had a chance to ask questions and get answers that make sense to you.  By signing this form you will not give up any 
legal rights. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. law. This Web site 
will not include information that can identify you. At most the Web site will include a summary of the results. You can 
search this Web site at any time. 
 
What is the purpose of this study? 
The purpose of this study is to look at Opioid Use Disorders (OUDs) and Vagal Nerve Stimulation (VNS). OUDs are 
conditions involving misuse or addiction to opiate-containing prescription pain medications or opioid-containing 
substances including heroin. OUDs are associated with symptoms of withdrawal upon discontinuation of the substance, 
which can include problems with concentration and sleep, irritability, rapid heart rate, and craving for opioids. Vagal 
Nerve Stimulation (VNS) is a procedure where the vagus nerve, which is in the neck, is electrically stimulated, much like 
a pacemaker is used to stimulate the heart. Branches of the vagus nerve travel throughout the brain and the body. Vagal 
nerve stimulation is felt to have positive effects on the brain and body by blocking the sympathetic (adrenaline) 
response that occurs with withdrawal from opioids, as well as changes in the brain that drive craving for opioids. A 
surgically implantable VNS has been approved by the Food and Drug Administration (FDA) for the treatment of both 
epilepsy and severe depression. Studies have shown that VNS stimulation is helpful for both conditions. We are using a 
non-invasive hand-held VNS device made by a company called ElectroCore. It is applied directly to the neck and does not 
require surgery. It is approved in Europe for the treatments of epilepsy, anxiety, depression, headaches, and other 
conditions, and in the US by the FDA for the treatment of headaches. We have studied its use at Emory for PTSD and 
have found it to be well tolerated and there have been no adverse events or untoward effects with the device. It has not 
yet been approved in the US by the FDA for the treatment of OUDs and is considered investigational in this study.  
 
 


 
 
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IRB Form 06162020 
You have been selected to participate in this study because you have been diagnosed with and Opioid Use Disorder 
(OUD). The main purpose of this study is to look at the effects of VNS on behavior as well as blood and brain responses 
to craving in patients with OUDs. Study procedures include a screening, mental health assessment, medical assessment, 
lab work, and brain imaging with and without VNS and opioid use related videos. Brain imaging will be done with 
positron emission tomography (PET) and Magnetic Resonance Imaging (MRI). It is possible that you may not have the 
brain imaging (PET and/or MRI) during the study. The study will be completed in up to 3 visits. 
 
What will I be asked to do? 
After signing the consent form, you will begin research procedures.  
 
Screening Description (Visit 1): If a screening was not done over the phone then you will be carefully screened during 
this study visit. You will be screened to make sure you qualify for the study and to make sure you do not have any 
contraindication to the brain imaging or other study procedures. If you qualify for the study, you may undergo an initial 
group of tests, which include questionnaires about your behaviors, experiences, and medical history. We may ask you to 
complete a urine drug test and we will also go over psychiatric questionnaires with you. These will be either be collected 
in paper form or using a computer or tablet. This visit, if needed, will take around 1-2 hours. 
 
We may also ask if you are willing to be a backup participant. If you are, we may ask you to come in for an hour or two 
on the PET day. If the scheduled participant is not able to complete the study then we would proceed for the full day 
with you. If the other participant is able to complete the study then we would reschedule your visit for another day. 
 
Visit 2 Description (PET Day): If not previously screened then you will begin with this. If you have been screened then 
you will undergo brain imaging using PET. We may ask you to hold all of your morning medications on the day of your 
testing. You may take these medications once you are done with the testing. Specific medications may exclude you from 
being qualified for the study. These medications may include antipsychotic or other psychotropic medication treatment 
during the last month.  You will be asked not to eat or drink anything except water for two hours before your visit. 
Please eat a light breakfast around 6am. Eight brain scans sessions will be performed using PET during one study visit 
with neutral and opioid use related videos. We will ask you about your medical history, health behaviors such as 
smoking status, clinical events and procedures, and medications. We will also ask questions about your mood and stress 
level. And we will go over psychiatric questionnaires with you. Blood and urine tests, including a urine pregnancy test if 
you are a woman of child bearing potential, will be done. Women who are positive for pregnancy will not be eligible for 
participation in this study. Blood vessel testing, VNS, physiological monitoring, and heart monitoring will be performed. 
You may be fitted with a Biopac monitor that will measure things like heart rate and skin temperature and/or fitted with 
a temperature-controlled glove-like patch at each visit. You may be given an activity monitor to wear on your wrist of 
either arm. This visit will occur at the Emory Center for Systems Imaging (CSI) and will take around 3-4 hours. You may 
be given a VNS device to take home for 4-6 weeks. A prepaid return mailer will be given to you. Successful return of the 
device will be included as a requirement for your study compensation.  
 
PET scan:  You will undergo PET scanning of your brain at the Emory Center for Systems Imaging (CSI).  A PET scan is an 
imaging system which provides a picture of the functioning or activated areas of the brain. You will also be wearing a set 
of noninvasive sensors on your body to measure physiological signals. These signals may include the following: brain 
activity, heart activity, blood vessel function, and skin activity and temperature. You will also be wearing the sensor on 
your finger for the PAT test during the scans and a pair of smart glasses that will allow you to view videos in the camera. 
Prior to the PET scan, a small needle (intravenous catheter or i.v.) will be placed in a vein in your arm to allow for the 
administration of radioactive water by a physician, nurse, or Nuclear Medicine Technologist and to allow for the blood 
collections. After the IV is in place, you will be asked to lie on a narrow table with your head inside of an open tunnel.  
The first scan will be to measure the position and size of your head.  You might hear a very faint sound during scanning 
(most people don’t hear anything).  The procedure will consist of eight PET scans of the brain. The scans will be done 
along with neutral and opioid use related videos and/or receiving VNS. You will receive either VNS or a fake or sham 


 
 
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IRB Form 06162020 
stimulation. You will be randomly assigned the order by a computer program. You have a 50/50 chance of ending up in 
either group. Blood samples will be drawn from the i.v. to measure molecules in the blood that may be involved in the 
stress response (for example: cortisol and norepinephrine and other biomarkers) at various time points during the study 
visit (a total of around 18 tablespoons). The PET procedure will take about 90 minutes, plus about a half hour of 
preparation time, and an hour and a half after the PET scans for blood draws.   
Visit 3 Description (MRI Day): You will undergo scanning of your head with MRI at the Emory Center for Systems 
Imaging (CSI). Magnetic Resonance Imaging (MRI) uses a powerful magnet to take pictures of your body. Because the 
MRI machine exposes the body to a very strong magnetic force, you will have to follow certain safety precautions to 
make sure you do not have any metal objects in or on your body. Before you undergo your MRI scan, a researcher or 
technician will ask whether or not your body contains any metallic medical devices or equipment, including heart 
pacemakers, metal prostheses, implants or surgical clips. You also will be asked whether you have had any prior injury 
from shrapnel or grinding metal, and you will be asked whether your eyes may have been exposed to metal particles. 
You or the researcher or technician will also complete a checklist that addresses issues of MRI safety. You will be asked 
to remove all jewelry and other metal-containing objects, like a belt. You will lie flat on a table with your head 
positioned in the scanner part of the machine for a little less than an hour. No part of the machine will come into contact 
with your body. When you are inside the scanner, you will be able to see out through a mirror. You will occasionally hear 
loud noises as the scanner takes pictures of your head. If you have a claustrophobic reaction to being scanned, you will 
be removed from the scanner. The whole session will take about 1 hour of your time. 
Follow up call: After 6 weeks, the study team may call you to see how you are doing. We may ask you to repeat a few of 
the questionnaires you completed during the study visits. If you took a VNS device home with you we will ask you a few 
questions about that and remind you to return this to us. 
Optional Studies 
 
Optional Study – future research: In the future, we would like to contact you to offer you the chance to participate in 
additional studies. This future contact would be made by one of the investigators, coordinators, or recruiters of this 
study. The contact would initially be made by phone, email, or by sending you a letter in the mail. This contact might 
include a questionnaire for you to fill out and return. If you do not want to participate or fill out the questionnaire, you 
will simply be asked to return a card in the mail to us, email, or call us. If we do not hear from you then we may have our 
study coordinator call you. There is no additional compensation for this future contact. 
 
Optional Study - Storage of Samples for Future Research: With your permission, we would like to store part of your 
blood sample in a freezer for future studies.  The sample will not be used for genetic testing.  If a future study were to be 
done, we may share the blood with other researchers.  Your sample will be stored for as long as it is useful, unless you 
ask us to destroy it sooner.  The Principal Investigator and members of the research team will have access to the 
samples.  The sample will be stored using your identification code, not your name or other identifying information. 
Donating blood is completely voluntary and will not affect your care in any way.  You can refuse to have your sample 
stored and still be able to participate in this study.  The information that is obtained from the study of your blood may 
be used by the sponsors of other research.  The study of your blood sample may contribute to the creation of new 
diagnostic tests or new medicines in the future.  However, you will receive no financial benefits from such developments 
nor will we be able to tell you the results of any tests run with your sample.   
 
Optional Study - Blood Sample Link: 
If you give us permission to store part of your blood sample, we will store it with an identification code. In order to 
protect your privacy, all samples from your blood will be given an identification code that does not include any of your 
personal information.  This code will allow researchers to link clinical information about you with your blood sample.  
Unless you disagree, the Principal Investigator will keep a private list that links your sample code with your name, 
allowing him/her to know which samples were collected from you. You can request that we not keep any information 


 
 
Page 6 of 13 
 
Version Date: 7/18/2022 
IRB Form 06162020 
linking your name with your sample. Please understand that once we lose the ability to know which sample(s) came 
from you, we also lose the ability to destroy your samples upon request, or to respond to any future requests you may 
make regarding results or new information.   If you allow the Principal Investigator to keep the list that links your sample 
code with your name then you may request that your sample be destroyed at any time by contacting the Principal 
Investigator, J. Douglas Bremner, MD at 404-712-9569. 
Who owns my study information and samples? 
If you join this study, you will be donating your samples and study information.  You will not receive any compensation if 
your samples or information are used to make a new product. If you withdraw from the study, data and samples that 
were already collected may be still be used for this study.   
 
What are the possible risks and discomforts? 
There may be side effects from the study procedures that are not known at this time. The most common risks and 
discomforts expected in this study are: (1) the stress of the psychological questionnaires/interview; (2) physiological 
monitors; (3) the intravenous catheters and blood draw; (4) the PET scan with a radioactive substance; (5) the MRI scan; 
(6) opioid use related videos; (7) VNS testing; (8) reproductive risks; (9) fasting.  
1. Psychological questionnaires/interview: Being asked questions about the stress in your life or your mood and 
opioid use may cause you to have unpleasant and/or upsetting feelings or have an increase in opioid craving.  If this 
happens, then you can take a break from the interviews.  You can also slow down and take longer to do the tests. If 
needed, an assessment by the study psychiatrist may be performed. A referral for treatment or assessment will be 
made available if needed.  
 
2. Physiological monitors: (Biopac, Glove, EDA, PPG, SCG, etc.) These monitors require you to have sensors attached 
to your skin which may represent an inconvenience to you e.g. when adhesives are removed. They may also cause 
mild skin irritation or itching. The glove cold application may cause temporary numbness, which stops after 
application. The hot application may cause temporary redness/skin sensitivity. You may feel itchiness due to sensor 
hookups on hands (due to sticky electrodes and gels) and temporary numbness of the arm is possible, since you will 
remain in the same position for half an hour. The EDA requires you to wear a bracelet-type device during (and 
possibly after) the visit, which may represent an inconvenience to you. 
 
3. Intravenous (IV) catheter and blood draw.  The IV can result in infection, bruising of the skin, or a blood clot in the 
vein.  These complications are not common when the catheter is inserted by a professional under clean conditions.  
Dizziness and fainting are rare risks of blood draws. There are no long-term side effects. You may have some 
discomfort from the blood drawing.  The risk from blood drawing is minimal, but may include bruising and infection.  
The use of sterile precautions will decrease the risk of infection.  However, you may develop a bruise at the site of 
the puncture, but this will go away in two to three days. If we are unable to get IV access then you may not be 
eligible for the study. 
 
4. PET scan:  This research study involves exposure to radiation from a Positron Emission tomography (PET) scan.  This 
PET scan procedure is routinely used for medical purposes; however, radioactive water is investigational and not 
approved by the FDA. This radiation dose is not necessary for your medical care and will occur only as a result of 
your participation in this study. If you have had any significant exposure to radiation over the past year or plan to 
participate in other research studies involving radioactivity over the next year please consult with the study team 
and Dr. Bremner first. Some people experience anxiety from the PET scan procedure. Viewing videos on smart 
glasses may cause wooziness or motion sickness. A nurse or technologist will be with you during the PET scan 
procedure. If you should become claustrophobic, anxious or agitated, or otherwise feel unwell in the PET scanner, 
the scan will be stopped.  If you are not able to complete the first PET scan, you may not be able to continue in the 
study.  This study will expose you to a small amount of radiation.  The radiation dose that you will receive is equal to 
or less than the annual radiation exposure limit allowed for persons who are occupationally exposed to radiation (x-
ray technicians, radiologist). The principal risk associated with a radiation dose is the possibility of developing a 


 
 
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IRB Form 06162020 
radiation-induced cancer later in life. The risk for radiation-induced cancer from this study is minimal. Although the 
risk from radiation is cumulative it is not expected to adversely affect your condition or treatment. The risk from 
radiation exposure of this magnitude is considered to be comparable to other everyday risks.  
5. MRI scan:  MRI is used routinely for diagnosis of medical conditions.  Although MRI, like X-ray, is used to take 
pictures of structures in the brain and other parts of the body, there is no radiation with MRI. If you have any metal 
in your body (such as shrapnel or a pacemaker), you may not be eligible for the study because it would be unsafe for 
you to have an MRI. An MRI scan can make some people feel anxious, particularly if they do not like enclosed spaces 
or noise.  If you feel very anxious or uncomfortable during the scanning, you should inform the study team and if 
needed the study will be stopped. You are free to stop the MRI at any time. This type of brain scan is not designed to 
detect problems of the brain. A radiologist will not be reading the scan. However, it is still possible that we will see 
something on your scan that is potentially abnormal, but may be nothing. If this happens, we will discuss it with you. 
This may cause you to seek further medical treatment and incur costs associated with that. 
 
You will be getting scans (PET/MRI) for research purposes only.  The research does not require the scans to be read 
for healthcare purposes. However, if the researchers are concerned about something they see on the scans they will 
tell you, and ask you if you want the scans to be reviewed for healthcare purposes (possibly by other clinicians), and 
you may then be referred for medical treatment.  You or your insurance company may have to pay for the review for 
healthcare purposes, and for any such treatment. 
 
6. Opioid Use Related Videos. The viewing of opioid use related videos may cause some anxiety or feelings of craving 
for opioids. You may stop this test at any time if you experience anxiety, excessive cravings, or other problems or are 
uncomfortable with the procedure. 
 
7. VNS Testing. Sometimes, you may experience hoarseness, shortness of breath, throat pain, cough, abdominal pain, 
headache, and/or change in voice during treatment. A tingling/pricking/twitching feeling where the device is applied 
is normal, but should not cause major discomfort. These effects usually stop right away once the treatment is 
completed. Mild skin irritation or dizziness are other possible side effects. We will not use the VNS device if you have 
any of the following conditions: an active implantable medical device, such as a pacemaker, defibrillator, cochlear 
implant, and other implanted electronic device; a history of significant carotid atherosclerosis; or a cervical 
vagotomy. 
 
8. Reproductive Risks. Women please note: Since this research may have bad effects on a fetus and should not be 
done during pregnancy, it is necessary that a pregnancy test be done first, even if, to the best of your knowledge, 
you are not pregnant now.  Women of childbearing potential will take a urine pregnancy test when you arrive for 
your visit.  If the test is positive you will not be able to participate in the study.  This study may be hazardous to a 
breast-feeding child.  Breast feeding mothers may not participate in this study. 
 
Women who may be pregnant should not be in this study because of possible effects of radiation exposure on their 
unborn child.  Both men who may later father children and women of childbearing potential should be aware that 
exposure to radiation poses a very slight risk of genetic mutation in the next generation. 
 
9. Fasting. In order to undergo study testing (PET day), you need to be fasting before your study visit until the scans are 
completed. Some people may show discomfort from this prolonged fasting, although true hypoglycemia is rare. A 
sweetened beverage will be administered if patients complain of lightheadedness or other fasting-related 
symptoms. 
 
It is possible that the researchers will learn something new during the study about the risks of being in it.  If this 
happens, they will tell you about it. Then you can decide if you want to continue to be in this study or not.  You may be 
asked to sign a new consent form that includes the new information if you decide to stay in the study. 


 
 
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Will I benefit directly from the study?  
This study is not designed to benefit you directly. This study is designed to learn more about the effects of VNS on 
behavior as well as blood and brain responses to stress. The study results may be used to help others in the future. In 
general, we will not give you any individual results from the study of the samples you give us. If we find something of 
urgent medical importance to you, we will inform you, although we expect that this will be a very rare occurrence. 
Will I be compensated for my time and effort? 
You will be compensated for your time and effort for participating in this study.  Compensation ranges from $75 to a 
total of up to $350 for the study. A breakdown of payments is listed below. We will also pay for parking, if needed, at 
each clinical visit.  The return of the VNS/Sham device is necessary for you to receive full compensation. 
If used as a backup participant: $50 to cover time and transportation costs 
Visit 2: $150 (PET Day) 
Visit 3: $75 (MRI Day) 
If you are given a VNS device to take home, you will get $75 after successful return of the device. 
You may be asked to fill out a tax form, including your Social Security or Taxpayer Identification Number, in order to be 
reimbursed, depending on the amount and method of payment. Some payment methods involve mail coming to your 
house, which may be seen by others in your household. Another method of payment is using “ClinCard”, which works 
like a debit card and is provided by Greenphire. When visits are completed, funds will be loaded onto your card. You will 
be able to use the funds in approximately 1 business day. You will have up to 3 visits over the period of the study (total 
that you can receive is $350). To issue your card, we need to give Greenphire some of your personal information. If you 
do not wish to provide this information, you can still take part in the study, but you will not be paid (or paid through a 
different mechanism if applicable). Banks and other financial institutions can access this information if they need to 
verify your identity when you use your card. Emory is required by law to report any payments we make to the IRS. To do 
this, the Finance department needs to keep your social security number on file. We are asking you to allow us to give 
your name, address, date of birth, research study name and social security number to Greenphire. If you want to receive 
email or text alerts when payments are made to you, we will ask you to provide your email or phone number as well. All 
of this information will be stored on computers owned by Greenphire. Greenphire will not have access to any other 
information collected during this study. Full instructions about using your card are included when we issue it. Please ask 
if you have any questions or concerns about the card or use of your personal information. You can decline payment if 
you are concerned about confidentiality, or you can talk to the study team to see if there are other payment options.  
What are my other options? 
If you decide not to enter this study, there is care available to you outside of this research study. This study is not 
designed to prevent or treat you. The alternative to participating in this study is to not participate. Emory, Grady and 
other healthcare facilities are available to provide care for your medical problems.   
 
How will you protect my private information that you collect in this study? 
Whenever possible, a study number, rather than your name, will be used on study records.  Your name and other 
identifying information will not appear when we present or publish the study results. 
Certificate of Confidentiality 
There is a Certificate of Confidentiality from the National Institutes of Health for this Study.  The Certificate of 
Confidentiality helps us to keep others from learning that you participated in this study.  Emory will rely on the 
Certificate of Confidentiality to refuse to give out study information that identifies you.  For example, if Emory received a 
subpoena for study records, it would not give out information that identifies you. 
 
The Certificate of Confidentiality does not stop you or someone else, like a member of your family, from giving out 
information about your participation in this study.  For example, if you let your insurance company know that you are in 


 
 
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this study, and you agree to give the insurance company research information, then the investigator cannot use the 
Certificate to withhold this information. This means you and your family also need to protect your own privacy. 
 
The Certificate does not stop Emory from making the following disclosures about you: 
 
• 
Giving state public health officials information about certain infectious diseases, 
• 
Giving law officials information about abuse of a child, elderly person or disabled person. 
• 
Giving out information to prevent harm to you or others. 
 
Giving the study sponsor or funders information about the study, including information for an audit or evaluation. 
 
Storing and Sharing your Information 
De-identified data from this study (data that has been stripped of all information that can identify you), including your 
de-identified genetic information, may be placed into public databases where, in addition to having no direct identifiers, 
researchers will need to sign data use agreements before accessing the data. We will remove or code any personal 
information that could identify you before your information is shared. This will ensure that, by current scientific standards 
and known methods, it is extremely unlikely that anyone would be able to identify you from the information we share. 
Despite these measures, we cannot guarantee anonymity of your personal data. 
Your data [and specimens] from this study may be useful for other research being done by investigators at Emory or 
elsewhere. To help further science, we may provide your deidentified data and/or specimens to other researchers. If we 
do, we will not include any information that could identify you. If your data or specimens are labeled with your study ID, 
we will not allow the other investigators to link that ID to your identifiable information. 
In general, we will not give you any individual results from the study of the samples you give us. If we find something of 
urgent medical importance to you, we will inform you, although we expect that this will be a very rare occurrence. 
Medical Record 
If you have been an Emory Healthcare patient before, then you already have an Emory Healthcare medical record.  If 
you have never been an Emory Healthcare patient, you do not have one.   An Emory Healthcare medical record will be 
made for you if an Emory provider or facility gives you any services or procedures for this study.   
 
Copies of the consent form/HIPAA authorization that you sign will be put in any Emory Healthcare medical record you 
have now or any time during the study.   
 
Emory Healthcare may create study information about you that can help with your care.  For example, the results of 
study tests or procedures.  These study results will be put in your Emory Healthcare medical record. Anyone who has 
access to your medical records will be able to have access to all the study information placed there.  The confidentiality 
of the study information in your medical record will be protected by laws like the HIPAA privacy rule.  State and federal 
laws may not protect the research information from disclosure.  
 
The results of some study tests and procedures will be used only for research purposes and will not be placed in your 
medical record.  For this study, those items include:  
• 
Labs – blood and urine testing 
• 
PET and MRI scans 
• 
Psychological/psychiatric assessments/interviews/questionnaires 
• 
Physiological monitoring 
• 
VNS testing 
 


 
 
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Tests and procedures done at non-Emory places may not become part of your Emory medical record. Also, if you decide 
to be in this study, it is up to you to let your other health providers know.  
 
In Case of Injury 
If you believe you have become ill or injured from this research, you should contact Dr. J. Douglas Bremner at telephone 
number 404-712-9569. You should also let any health care provider who treats you know that you are in a research 
study. 
 
If you get ill or injured from being in the study, Emory will help you get medical treatment. Neither Emory nor the study-
supporter will pay for your medical treatment.  Your insurer will be billed for your treatment costs.  If you do not have 
insurance, or if your insurance does not pay, then you will have to pay these costs.      
 
Emory and the study supporter have not, however, set aside any money to pay you or to pay for this medical treatment. 
The only exception is if it is proven that your injury or illness is directly caused by the negligence of an Emory or sponsor 
employee.  “Negligence” is the failure to follow a standard duty of care. You do not give up any legal rights you may 
have by being in this study, including any right to bring a claim for negligence. 
 
Costs 
There will be no costs to you for participating in this study, other than basic expenses like transportation. You will not be 
charged for any of the research activities. If the study procedures result in any medical complications that would not fall 
under “injury” as discussed above, the cost of treatment for those complications may be charged to you or your 
insurance.   
 
Withdrawal from the Study 
You have the right to leave a study at any time without penalty. The researchers also have the right to stop your 
participation in this study without your consent for any reason. Especially if they believe it is in your best interest or if you 
were to object to any future changes that may be made in the study plan. 
 
Authorization to Use and Disclose Protected Health Information 
 
The privacy of your health information is important to us.  We call your health information that identifies you, your 
“protected health information” or “PHI.”  To protect your PHI, we will follow federal and state privacy laws, including the 
Health Insurance Portability and Accountability Act and regulations (HIPAA).  We refer to all of these laws as the “Privacy 
Rules.”  Here we let you know how we will use and disclose your PHI for the main study and for any optional studies in 
which you may choose to participate. 
 
Main Study 
PHI that Will be Used/Disclosed:   
The PHI that we will use or share for the research study includes: 
• 
Demographic information such as your name, date of birth, and other identifiers 
• 
Medical information about you including your medical history and present/past medications. 
• 
Results of exams, procedures and tests you have before and during the study. 
Purposes for Which Your PHI Will be Used/Disclosed: 
We will use and share your PHI for the conduct and oversight of the research study.  We will use and share your 
PHI to provide you with study related treatment and for payment for such treatment.  We will also use and 
share your PHI to conduct normal business operations.  We may share your PHI with other people and places 
that help us conduct or carry out the study, such as laboratories, data management centers, data monitors, 


 
 
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contract research organizations, Institutional Review Boards (IRBs) and other study sites. If you leave the study, 
we may use your PHI to determine your health, vital status or contact information.  
 
Use and Disclosure of Your Information That is Required by Law:   
We will use and disclose your PHI when we are required to do so by law. This includes laws that require us to 
report child abuse or abuse of elderly or disabled adults. We will also comply with legal requests or orders that 
require us to disclose your PHI. These include subpoenas or court orders.   
 
Authorization to Use PHI is Required to Participate: 
By signing this form, you give us permission to use and share your PHI as described in this form. You do not have 
to sign this form to allow the use and disclosure of your PHI.  If you do not sign this form, then you may not 
participate in the research study.   
 
People Who will Use/Disclose Your PHI: 
The following people and groups will use and disclose your PHI in connection with the research study: 
• 
The Principal Investigator and the research staff will use and share your PHI to conduct the study  
• 
Emory may use and disclose your PHI to get payment for study procedures and to run normal business 
operations.  
• 
Greenphire, an independent company specializing in payments for research studies and clinical trials.  
• 
The Principal Investigator and research staff will share your PHI with other people and groups to help 
conduct the study or to provide oversight for the study. 
• 
Doug Bremner, MD is the Sponsor of the study.  The Sponsor may use and disclose your PHI to make 
sure the research is done correctly and to collect and analyze the results of the research.  The Sponsor 
may disclose your PHI to other people and groups like study monitors to help conduct the study or to 
provide oversight for the study.   
• 
The National Institute on Drug Abuse (NIDA) is the study supporter. The study supporter may use and 
disclose your PHI to make sure the research is done correctly and to collect the results of the research.  
The study supporter may disclose your PHI to other people and groups like study monitors to help 
conduct the study or to provide oversight for the study.   
• 
The research team and the Sponsor may use and disclose your PHI, including disclosure to insurance 
carriers to administer payment for subject injury.  
• 
The following people and groups will use your PHI to make sure the research is done correctly and 
safely: 
• 
Emory offices that are part of the Human Research Participant Protection Program and those 
that are involved in study administration and billing.  These include the Emory IRB, the Emory 
Research and Healthcare Compliance Offices, and the Emory Office for Clinical Research. 
• 
Government agencies that regulate the research including:  Office for Human Research 
Protections or the Food and Drug Administration. 
• 
Public health agencies. 
• 
Research monitors and reviewer. 
• 
Accreditation agencies. 
• 
Georgia Institute for Technology IRB 
• 
Sometimes a Principal Investigator or other researcher moves to a different institution. If this happens, 
your PHI may be shared with that new institution and their oversight offices. PHI will be shared securely 
and under a legal agreement to ensure it continues to be used under the terms of this consent and 
HIPAA authorization. 
 
 


 
 
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Optional Studies: future research, storage of samples for future research, and blood sample link: 
PHI That Will be Used/Disclosed for Optional Studies:   
The PHI that we will use and/or disclose (share) for the optional research studies includes: The same people and 
groups who will use and disclose your PHI for the main study will also do so in connection with the optional 
research study.  
Purposes for which your PHI will be Used/Disclosed for Optional Studies: 
We will use and disclose your PHI for the conduct and oversight of the optional research study. 
 
Authorization for This Use of PHI is Required to Participate in Optional Studies, but Not in Main Study: 
You do not have to authorize the use and disclosure of your PHI.  If you do not authorize the use and disclosure 
of your PHI for the optional studies, then you may not participate in the optional research studies.  You can still 
be in the main research study even if you don’t participate in the optional studies.    
 
People Who Will Use/Disclose Your PHI for Optional Studies: 
The following people and groups will use and disclose your PHI in connection with the optional research studies: 
• 
The same people and groups who will use and disclose your PHI for the main study will also do so in 
connection with the optional research study. 
• 
Future researchers 
Expiration of Your Authorization 
We will add your PHI to a database that we are compiling for research purposes.  There is no date or event after which 
your authorization will expire and your PHI will no longer be used for this purpose. 
 
Revoking Your Authorization 
If you sign this form, at any time later you may revoke (take back) your permission to use your information.  If you want 
to do this, you must contact the principal investigator at: 
J Douglas Bremner, MD 
Professor of Psychiatry and Radiology 
12 Executive Park Dr NE, Room 382 
Atlanta, GA 30329 
 
At that point, the researchers would not collect any more of your PHI.  But they may use or disclose the information you 
already gave them so they can follow the law, protect your safety, or make sure that the study was done properly and 
the data is correct.  If you revoke your authorization you will not be able to stay in the main study.  
 
Other Items You Should Know about Your Privacy 
Not all people and entities are covered by the Privacy Rules.  HIPAA only applies to health care providers, health care 
payers, and health care clearinghouses.  If we disclose your information to people who are not covered by the Privacy 
Rules, including HIPAA, then your information won’t be protected by the Privacy Rules.  People who do not have to 
follow the Privacy rules can use or disclose your information with others without your permission if they are allowed to 
do so by the laws that cover them.   
 
To maintain the integrity of this research study, you generally will not have access to your PHI related to this research 
until the study is complete.  When the study ends, and at your request, you generally will have access to your PHI that 
we maintain in a designated record set.  A designated record set is data that includes medical information or billing 
records that your health care providers use to make decisions about you. If it is necessary for your health care, your 
health information will be provided to your doctor.  
 


 
 
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We may remove identifying information from your PHI.  Once we do this, the remaining information will not be subject 
to the Privacy Rules.  Information without identifiers may be used or disclosed with other people or organizations for 
purposes besides this study.   
Contact Information 
Contact Emily Driggers, Research Associate, at 770-558-0189, or emily.g.driggers@emory.edu: 
• 
if you have any questions about this study or your part in it,   
• 
if you feel you have had a research-related injury or a bad reaction to the study procedures, or 
• 
if you have questions, concerns or complaints about the research 
Contact the Emory Institutional Review Board at 404-712-0720 or 877-503-9797 or irb@emory.edu: 
• 
if you have questions about your rights as a research participant. 
• 
if you have questions, concerns or complaints about the research. 
• 
You may also let the IRB know about your experience as a research participant through our Research Participant 
Survey at http://www.surveymonkey.com/s/6ZDMW75. 
 
Consent and Authorization 
Consent and HIPAA Authorization for Optional Studies:   
Please initial below if you opt to participate in and authorize use and disclosure of your PHI in the optional studies 
previously described: 
 
Future Research ____________Initials  
 
 
Storage of Samples for Future Research ____________Initials 
 
 
Blood Sample Link ______________Initials 
 
TO BE FILLED OUT BY SUBJECT ONLY 
Please print your name, sign, and date below if you agree to be in the main study. By signing this consent and 
authorization form, you will not give up any of your legal rights. We will give you a copy of the signed form to keep. 
 
 
 
Name of Subject  
 
 
 
 
 
  
Signature of Subject (18 or older and able to consent) 
Date              Time 
 
TO BE FILLED OUT BY STUDY TEAM ONLY 
 
__________________________________________________________ 
Name of Person Conducting Informed Consent Discussion 
 
 
 
 
 
 
Signature of Person Conducting Informed Consent Discussion  
 
  Date              Time