Clinical trial NCT03846505
Conditions: Alcohol Use Disorder Couples
Keywords: Couple Alcohol Therapy
Sponsor: Medical University of South Carolina
Start date: 2019-05-16; Completion date: 2024-01-31
Enrollment: 192 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Alcohol Behavioral Couples Therapy (ABCT) is a manualized 12-session, weekly psychosocial intervention that simultaneously reduces alcohol use disorder (AUD) severity and improves relationship functioning. However, there remains room to improve ABCT outcomes. A growing literature suggests that intranasal oxytocin is a medication that holds promise to achieve that goal. Oxytocin has demonstrated the ability to increase prosocial behavior (e.g., trust, safety, social cognition) and restore sensitivity to natural rewards such as interpersonal relationships that are commonly eroded in the context of addiction. Oxytocin has also demonstrated the ability to reduce substance use behaviors (e.g., craving, self-administration, tolerance, withdrawal), and improves the neurobiological foundations of AUD. The primary objective of this Stage II study is to test the efficacy of oxytocin versus placebo in improving (1) AUD symptom severity, (2) relationship functioning, and (3) corticolimbic connectivity among couples receiving ABCT therapy.

Detailed description:

Arms: arm 1: A 40-IU dose of oxytocin will be self-administered 30 minutes prior to the start of each weekly ABCT session.

All participants will receive 12 weekly, 90-minute ABCT therapy sessions delivered by trained Masters or Doctoral-level clinicians consistent with the published manual. arm 2: A placebo will be self-administered 30 minutes prior to the start of each weekly ABCT session.

All participants will receive 12 weekly, 90-minute ABCT therapy sessions delivered by trained Masters or Doctoral-level clinicians consistent with the published manual.
Interventions: intervention 1: Oxytocin intervention 2: Placebo
Intervention descriptions: intervention 1: A 40-IU dose of oxytocin will be self-administered 30 minutes prior to the start of each weekly ABCT session. intervention 2: A placebo will be self-administered 30 minutes prior to the start of each weekly ABCT session.

Protocol documents:
Prot_SAP_000.pdf: 
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PROTOCOL TITLE: Oxytocin to Enhance Alcohol Behavioral Couple Therapy  
 
PRINCIPAL INVESTIGATOR: Julianne Flanagan, Ph.D. 
 
ClinicalTrials.gov ID: Pro00082233 
 
Document Date: March 8, 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.0 
Objectives / Specific Aims 
Identifying effective medications to treat alcohol use disorder (AUD) is a national public health 
priority. Combining pharmacological interventions with evidence-based behavioral treatments may help 
maximize and sustain AUD treatment outcomes1-3.  Alcohol Behavioral Couples Therapy (ABCT4) is a 
manualized, evidence-based psychotherapy for the treatment of AUD5-7 that simultaneously targets 
relationship functioning, which is an important mechanism in the etiology, course, and treatment of AUD8,9. 
While adaptive relationship functioning facilitates successful treatment engagement and outcomes9-11, 
maladaptive relationship functioning interferes with AUD recovery12-15 and is a precipitant of relapse16,17. 
Thus, ABCT employs cognitive behavioral techniques to (1) reduce alcohol consumption, (2) enhance 
partners’ skills to facilitate recovery (e.g., communication, managing cravings together), and (3) enhance 
relationship functioning. Although ABCT is a highly efficacious treatment, there is room for improvement 
in outcomes, as more than half of ABCT patients report hazardous drinking episodes during treatment and 
a similar proportion fail to achieve abstinence5,6,18,19.  
The neuropeptide oxytocin is a promising candidate to enhance ABCT via neurobiological and 
behavioral pathways including its potential to restore sensitivity to natural rewards such as interpersonal 
relationships20. Neuroimaging studies indicate that dysregulation of corticolimbic brain circuitry is centrally 
involved in AUD pathophysiology21,22. Individuals with AUD demonstrate lower corticolimbic 
connectivity than healthy controls23,24 and disrupted corticolimbic connectivity is associated with AUD 
relapse25. Notably, oxytocin increases corticolimbic connectivity26-29. Behaviorally, human and animal 
studies indicate that oxytocin reduces alcohol withdrawal, tolerance, craving and self-administration30-35. 
However, emerging literature emphasizes individual differences such as sex, social context, and 
psychosocial history that moderate the effects of oxytocin on social behavior36-41. Pilot data from our team 
revealed that among distressed couples with substance use disorders, oxytocin was associated with worse 
conflict behaviors among female partners, but did not affect male partners’ behavior42. These nuanced 
findings may be explained by the social salience hypothesis43, which proposes that rather than selectively 
enhancing prosocial behavior, oxytocin might universally amplify an individual’s current social tendencies 
which, in the context of addiction and relationship distress and without corrective intervention, may be 
maladaptive 8,13,17. ABCT has demonstrated the ability to insulate couples from maladaptive relationship 
behaviors that are proven antecedents to hazardous drinking and relapse by cultivating and implementing 
new adaptive skills that facilitate recovery 44,45. Notably, treatment gains are greater among couples who 
begin ABCT with poorer relationship functioning and greater psychiatric comorbidity5 and within-session 
gains predict positive ABCT outcomes 44. Thus, a key approach to the therapeutic translation of oxytocin 
is to combine oxytocin with a behavioral intervention such as ABCT to reduce alcohol consumption. Doing 
so will ensure that oxytocin has an adaptive platform to enhance the positive gains made within ABCT 
sessions. 
The proposed study will test the efficacy of oxytocin to enhance ABCT outcomes. We will also 
determine the effects of treatment on corticolimbic connectivity using blood oxygen level dependent 
(BOLD) functional magnetic resonance imaging (fMRI). In order to accomplish this, we will employ a 
double-blind, placebo-controlled, randomized study design and examine standardized, repeated, dependent 
measures of change in: (1) alcohol consumption, (2) relationship functioning, and (3) corticolimbic 
connectivity in response to a validated in-scanner cue paradigm. Couples (N=100) will be randomly 
assigned to receive oxytocin (40 IU) or placebo prior to each of 12 weekly ABCT therapy sessions. The 
following specific aims are proposed: 
 


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Specific Aim 1: Compare the efficacy of ABCT with oxytocin vs. placebo in reducing alcohol 
consumption.   
Specific Aim 2: Compare the efficacy of ABCT with oxytocin vs. placebo in improving relationship 
functioning. 
Specific Aim 3: Use neuroimaging to determine the effects of treatment on corticolimbic connectivity in 
response to alcohol and relationship conflict cues. 
 
2.0 
Intervention to be studied 
 
Study Medication, Dosage, and Administration. A 40-IU dose of oxytocin or matching placebo will be 
self-administered 30 minutes prior to the start of each weekly ABCT session. The dose and timing of 
medication administration is based on past research in our group and others46,47,82,117,118, and determined 
in consultation with NIAAA program staff. Study prescribers (Anjinetta Johnson, P.A. and Jennifer Jones, 
M.D.) will conduct the H&P exams, provide prescriptions for oxytocin, and assist with weekly assessment 
of adverse events. Investigational Drug Services (IDS) at MUSC or Pitt Street Pharmacy in Mt. Pleasant 
will compound and dispense oxytocin and matching placebo. Research staff will instruct participants on 
the correct method of administration to achieve the desired dose and will observe participants’ self-
administration. Participants will blow their nose, exhale through their nose, then spray into one nostril 
while inhaling, alternating nostrils until the 40 IU dose is achieved. A 40 IU dose has demonstrated 
extensive safety and efficacy, is within the normal dosing range, and one of the most common 
concentrations utilized in human research45,119,120 Randomization will be carried out by a research 
pharmacist not involved in clinical management of participants in order to preserve the double-blind 
design.  
 
Psychosocial Intervention: Alcohol Behavioral Couple Therapy (ABCT25). All participants will 
receive 12 weekly, 90-minute ABCT therapy sessions delivered by trained Masters or Doctoral-level 
clinicians consistent with the published manual25. The main goal of ABCT is to concurrently reduce AUD 
symptom severity and improve relationship functioning. Patients receive psychoeducation pertaining to 
the interconnectedness of AUD and relationship functioning. AUD-focused components of the treatment 
help patients identify and manage cravings, urges to drink, and thoughts about alcohol use; enhance 
individual problem solving and decision-making abilities; identify and plan for “high-risk” situations in 
which vulnerability to relapse is heightened; learn drink refusal skills; and cope with a potential relapse. 
ABCT also teaches couples to work together to enhance reciprocity and communication skills in the 
relationship, increase positive rewards of initiating and maintaining drinking reductions and abstinence, 
and identifying and implementing ways partners can help minimize and manage alcohol use triggers, 
participate in drink refusal skills, and help prevent relapse. 
 
3.0 
Study Endpoints  
Primary Outcome Measures. Primary outcomes include (1) alcohol consumption (percent days abstinent 
and heavy drinking as measured by the TLFB) and (2) relationship functioning (DAS-7). Additional AUD 
outcomes include alcohol craving (PACS) and ethanol metabolites and traditional biomarkers (e.g., EtG 
and PEth) to corroborate participant self-reports of abstinence and alcohol use121-123. PEth is among the 
most specific biomarkers used to detect heavy drinking and monitor abstinence124-126. The conjugated 
alcohol metabolite EtG remains positive in urine for several days following cessation and is a useful 
biomarker of recent drinking in outpatient settings127. Selected assessment instruments are standardized, 
have good psychometric properties, are widely used, and have been used extensively by our research group. 
 
AUD Symptom Severity  


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• Time Line Follow-Back (TLFB128): The TLFB, which uses a calendar to stimulate recall, will assess 
consumption of alcohol (e.g., number of standard drink units, percent of days drinking and abstinence, 
time span in which drinks were consumed), drugs, and tobacco for 60 days prior to study entry, and 
during the treatment and follow-up phase. 
Relationship Functioning 
• Dyadic Adjustment Scale-7 (DAS-7129): The self-report DAS-7 is based on the original 32-item 
measure130. It is used to assess domains relationship functioning and has demonstrated strong 
psychometric properties129.  
 
4.0 
Inclusion and Exclusion Criteria/ Study Population 
 
All participants will be at least 18 years of age. Women and members of minority groups will be eligible 
for participation. 
 
Inclusion criteria are: 1) aged 18- 75, 2) English fluency and intellectual functioning sufficient to provide 
informed consent and accurately complete assessments and participate in treatment (as assessed by a 
criterion of < 26 on the Mini-Mental Status Exam [MMSE]131), , 4) married, cohabiting, or in a committed 
relationship for ≥ 6 months, 5) one partner must meet DSM-5 diagnostic criteria for current (i.e., past 12 
months) alcohol use disorder (assessed via the Quick Structured Clinical Interview for DSM-5 Disorder). 
Couples in which both partners meet diagnostic criteria for current AUD are eligible for participation, 6) 
maintenance of psychotropic medications on a stable dose for at least 4 weeks before study initiation, and 
5) concurrent substance use disorders (e.g., marijuana) are acceptable provided that alcohol is the 
participant’s primary substance of choice. The inclusion of participants with substance use disorders is 
essential because of the marked frequency of co-occurrence among patients with AUD.  
 
Exclusion criteria include: 1) meeting DSM-5 criteria for a history of or current psychotic or bipolar 
affective disorders, 2) current suicidal or homicidal ideation and intent, 3) a history of seizures and/or a 
seizure disorder per the judgement of the medical clinician, 4) severe, unilateral intimate partner violence 
in the past 6 months as defined by the Revised Conflict Tactics Scale132, and 5) pregnancy or breastfeeding 
for women, 6) Acute alcohol withdrawal as indicated by CIWA-Ar scores >8, Attendance at therapeutic 
activities other than study sessions will be closely monitored using the Treatment Services Review, 7) any 
unstable or serious medical condition affecting the potential participant’s ability to participate in the study, 
8) Individuals with claustrophobia; tattoos above the shoulders; permanent eyeliner or permanent artificial 
eyebrows; cardiac pacemaker; metal fragments in eye, skin, or body, including shrapnel; heart valve 
replacement; brain clips; venous umbrella; current or former sheet-metal worker or welder; lifetime history 
of aneurysm surgery; lifetime history of seizures and/or epilepsy per the judgement of the medical clinician; 
intracranial bypass, renal, or aortic clips; prosthetic devices such as middle ear, eye, joint, or penile implants; 
joint replacements; non-removable hearing aid, neurostimulator, or insulin pump; shunts/stents; metal 
mesh/coil implants; metal plate/pin/screws/wires; or any other MRI contraindications as determined by the 
MRI technician at the time of scanning will not be eligible to participate in the neuroimaging component of 
the study, however individuals who meet inclusion/exclusion criteria for the medication component of the 
study but not the MRI portion will still be eligible to reenroll in and complete the medication/treatment phase.  
 
5.0 
Number of Subjects 
 
100 couples will be enrolled (200 total participants).  
 
 


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6.0 
Setting 
 
All procedures will be conducted on the MUSC campus or in VA research offices. Procedures can also be 
conducted via telehealth.  
 
7.0 
Recruitment Methods 
 
Recruitment sites will include the Center for Drug and Alcohol Programs (CDAP) at MUSC, the Ralph H. 
Johnson VAMC Substance Treatment and Recovery (STAR) clinic, and other in state and out of state VA 
clinics (e.g., Savannah CBOC). CDAP, directed by Dr. Joshua Smith, is an inpatient and outpatient 
addictions treatment facility with approximately 398 inpatient and 880 outpatient annual admissions. There 
were 1,279 new CDAP admissions in 2017 (~106/month) with the majority of patients (75-80%) seeking 
AUD treatment. The STAR clinic is directed by Dr. Karen Hartwell and Dr. Back (Co-I) is a Staff 
Psychologist in STAR. Consults for treatment are made directly to the STAR intake team. In 2017, STAR 
delivered 1,460 unique patient visits (682 AUD patients; 56 patients/month). An additional recruitment site 
will be the outpatient Ralph H. Johnson VAMC Couples and Family Clinic, directed by Dr. Julian Libet. 
The Couples and Family Clinic received 433 and 408 unique patient intakes in 2016 and 2017, respectively. 
We need to enroll 2-4 couples per month to complete the study within the proposed timeline. No other 
studies are enrolling couples at the proposed recrutiment sites. Thus, there should be no difficulty recruiting 
an adequate sample. Participants will also be recruited through IRB-approved flyers posted in (a) VAMC 
Women’s Health Clinic, Primary Care Clinic, and Emergency Department; (b) affiliated community based 
outpatient clinics; and (c) MUSC treatment clinics. Finally, we will place advertisements on social 
networking sites (e.g., Craigslist, Facebook), in local newspapers, and television. Participants who refer 
others to the study will be compensated $10 per randomized referral, allowing us to reach a wider pool of 
potential participating couples. Further, participants from past MUSC research studies who have consented 
to be contacted for future research studies will be recruited. These individuals will be referred to us via 
other MUSC researchers, or they may have indicated consent to be contacted about future research studies 
within their MUSC medical records. Our research team has successfully used these methods in previous 
and ongoing clinical trials among individuals and couples with AUD.  
 
College students ages 18-75 enrolled at area colleges and universities will be contacted from respective 
registrar lists (no participants will be recruited until an interinstitutional agreement is signed by the 
respective institution, submitted as an amendment to the MUSC IRB, and approved by the MUSC IRB). 
Potential participants will be sent a recruitment email that includes details about the study (e.g., time 
requirement, basic inclusion criteria, compensation), a link to the IRB approved screener, and contact 
information for the research team will be included in the email. Potential participants will also be contacted 
via phone.  
Chart review and EPIC/VINCI lists will be used for recruitment; only individuals who have previously 
agreed to be contacted for research opportunities will be identified. The study team will use an IRB 
approved letter and script will be used to inform identified individuals about our study. 
 
Participants will be recruited and enrolled from all 50 states. The protocol/NIH grant application was 
written pre-COVID 19, where we had various recruitment methods that included in-person collaboration 
with providers and clinics, as well as physical methods of recruitment (like flyering) from community 
locations (bars and clinics, etc). Since the COVID 19 pandemic, the climate of clinical trial recruitment 
has shifted drastically and reaching potential participants has moved almost fully virtual/digital. With the 
shift in recruitment methods, the market has become saturated throughout most of our social media 
outlets. We have also difficulty getting new methods of recruitment strategies/platforms approved by 


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MUSC/SC purchasing restrictions. Thus, the inclusion of participants out of state increases the pool of 
potential participants, helping to mitigate the impacts of COVID19. 
Further, the inclusion of out of state participants allows us to enroll more veterans referred through the 
VA system, as Savannah CBOC is part of the RHJVA.  
Also, out of state recruitment allows for a more diverse study sample. Recruitment of out of state 
participants will be accomplished through social media advertisements targeted at out of state areas. The 
advertisements will include our study screener. Study staff will connect with the potential participant 
based on the method of contact indicated by the participant on the screener. Our study contact information 
will also be provided should the participant not want to provide contact information for themselves. 
 
 
 
8.0 
Consent Process 
 
Potential participants will be given a full description of the study procedures and asked to read and 
sign an IRB-approved informed consent form before any study procedures or assessments are conducted. 
Individuals who were recruited from the VA will also be required to read and sign a VA R&D –approved 
consent. Additionally, VA participants and their partners who are recruited from the VA will only be 
consented by study staff who have an active WOC or VA appointment. Informed consent will take place 
on the MUSC campus or via telehealth, using an IRB approved platform, such as Doxy.Me or RedCap. 
Initial eligibility screening will be conducted by the PI, Co-Is, Coordinator, or a trained research assistant 
by telephone or in person. If preliminary inclusion and exclusion criteria are met, staff will schedule an 
assessment appointment for the couple. In a private room apart from their partner, participants will be 
provided with a description of the nature and requirements of study participation, and asked to read and 
sign an IRB-approved consent form prior to beginning any study procedures  In the event of eConsent, the 
informed consent process will still take place privately. If couples do not have the ability to each have a 
private room for eConsent (within their residence(s), separate appointments may be arranged to maintain 
privacy and to meet with each individual partner separately.  In the case of a VA consent, a VA consent 
document will either be mailed or emailed to the participant.  PI/study team will use government furnished 
equipment to video call with the participant and go over the document.  Once the document is signed, the 
participant will be asked to hold it up to the screen and a screenshot will be taken and saved for records.  
VA participants and their partners who are recruited from the VA will be given a VA Notice of Privacy 
Practices in addition to a copy of their consent. 
 
9.0 
Study Design / Methods 
Figure 1 below illustrates the study design. 
 
 
 
 
 
 
 
 
 
Overview. The proposed study is a 12-week, Stage-II, double-blind RCT examining the efficacy of 
combining oxytocin (40 IU) with ABCT in the treatment of AUD. A repeated measures design with two 
intervention arms will be used: ABCT + oxytocin compared to ABCT + placebo (Figure 1). 
 
fMRI and Blood 
Draw 
Informed Consent 
& Baseline 
Assessment  
fMRI and Blood 
Draw 
Randomization 
Oxytocin n= 50 
Placebo n= 50 
3 & 6 Month 
Follow-up 
Weekly ABCT Sessions +  
Oxytocin or Placebo  
Treatment Phase: ABCT Sessions 1-12 


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General Procedures. Following phone screening for preliminary eligibility, participants will complete a 
baseline assessment. In a private room apart from their partner, participants will be given a full description 
of the study procedures and asked to read and sign an IRB-approved informed consent form before any 
study procedures are conducted. In the event of telehealth, separate appointments will be made to meet with 
each individual partner separately. Consent will be conducted by trained staff (PI, Co-Is, Study Coordinator, 
or Research Assistant). Ineligible participants will be given treatment referrals as needed. During 1-2 
baseline visits, participants will complete a breathalyzer or alcohol saliva test strip (to test current BAC), 
pregnancy test (for women), ethyl glucuronide (EtG) and phosphatidyl ethanol (PEth) testing, a history and 
physical (H&P) exam, urine drug screen (UDS), a battery of standardized self-report and interview 
measures (Table 1).,. Note that for telehealth participants, biological specimens will not be collected, 
however, female participants will be required to take a pregnancy test (provided by study staff) and will be 
required to verbally confirm a negative result prior to continuing with any procedures. H&P exams will 
include a physical and neurological examination; orthostatic blood pressure and pulse measurements; and 
weight and BMI calculation. In the event of telehealth baseline appointment, biological measures will not 
be collected.  Provided full eligibility criteria are met, participants will schedule visits to complete script 
development needed for the fMRI sessions and a fMRI session (described in the Neuroimaging Procedures 
section). Participants will then enter the treatment phase, which is a 12-week, double-blind, placebo 
controlled RCT during which they will receive weekly ABCT therapy sessions in combination with 
oxytocin or placebo (see Study Interventions and Procedures Section). Intranasal oxytocin has a half-life of 
approximately 3-4 hours and can be stored, refrigerated, for 2-4 weeks. If a participant misses multiple 
appointments, a new dose may be dispensed from IDS or Pitt Street Pharmacy. Participants will complete 
3- and 6-month follow-up visits. AUD symptoms, relationship functioning, associated problems (e.g., 
depression), UDS, EtG, and adverse events will be assessed weekly. In addition, participants will be asked 
to complete a breathalyzer/alcohol saliva test strip while in the same room; after which they will be taken 
to separate rooms until it is time for therapy.  PEth will be examined at baseline, weeks 6 and 12, and at 
both follow-up assessments. Blood samples will be refrigerated until sent to out for assay. Therapy sessions 
may be videotaped, with participant consent. In order to explore secondary outcomes such as the effects of 
treatment on within-session behaviors, we will employ observational coding to assess frequency of positive, 
negative, and alcohol change talk behaviors (using the SCCIT-A133) in ABCT sessions 1, 4, 8, and 12.  
 
Table 1. Assessment Instruments and Timeline 
Instrument 
Purpose 
BSL Weekly Week  
6 
Week 
12 
3M 
F/U 
6M 
F/U 
Demographics Form 
Characterize sample 
X 
 
 
 
 
 
Mini Mental Status Exam (MMSE)131 
Screen for cognitive deficits 
PRN 
 
 
 
 
 
Quick Structured Clinical Interview for DSM-5 Disorders 
Assess DSM-5 psychiatric disorders 
X 
 
 
 
 
 
Concomitant Medications Form 
Assess concomitant medications 
X 
X 
X 
X 
X 
X 
Time Line Follow-Back (TLFB)128 
Primary outcome: AUD 
X 
X 
X 
X 
X 
X 
Penn Alcohol Craving Scale (PACS135) 
Assess alcohol craving 
X 
X 
X 
X 
X 
X 
Alcohol Use Disorders Identification Test (AUDIT)136 
Assess alcohol problems 
X 
 
X 
X 
X 
X 
Alcohol Dependence Scale (ADS)137 
Assess domains affected by AUD 
X 
 
 
X 
X 
X 
Readiness to Change Questionnaire (SOCRATES138) 
Assess readiness to change AUD 
X 
 
X 
X 
X 
X 
Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar)139 
Assess alcohol withdrawal 
X 
X 
 
 
X 
X 
Traumatic Life Events Questionnaire (TLEQ) 140 
Assess Trauma History 
X 
 
 
 
 
 
PTSD Checklist (PCL-C) 141 
Assess PTSD symptoms 
X 
 
 
X 
X 
X 
Beck Depression Inventory-II142 
Assess depression 
X 
X 
X 
X 
X 
X 
Cognitive Emotion Regulation Questionnaire; CERQ-Short 143 
Assess emotion regulation 
X 
 
 
X 
X 
X 


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Dyadic Adjustment Scale-short form (DAS)129 
Primary outcome: Relationship 
functioning 
X 
X 
X 
X 
X 
X 
Infidelity Assessment 144 
Assess Infidelity 
X 
 
 
X 
X 
X 
Revised Conflict Tactics Scale132 
Assess intimate partner violence 
X 
 
X 
X 
X 
X 
Reasons for Violence Scale145 
Assess reasons for partner violence 
X 
 
 
X 
X 
X 
Treatment Services Review 
Monitor service utilization 
 
X 
X 
X 
X 
X 
Helping Alliance Questionnaire, Therapist and Client Version146 
Asses therapeutic alliance 
 
X 
X 
X 
 
 
Treatment Adherence  
Assess homework compliance 
 
X 
X 
X 
 
 
History of Head Injuries 
Assess fMRI eligibility 
X 
 
 
X 
 
 
Drinking goals 
Assess treatment goals for alcohol 
X 
 
 
 
 
 
Coping Questionnaire 
Assess coping skills 
X 
 
 
 
 
 
Marijuana Motives 
Assess marijuana use 
X 
 
 
 
 
 
Visual Analog Scale (VAS) 
Asses alcohol craving 
X 
 
 
X 
 
 
Telehealth Questionnaire 
Asses telehealth  
 
 
 
X 
 
 
Psychological Stress Associated with COVID-19 Crisis Questionnaire 
Assess stress related to COVID-19 
X 
 
 
 
 
 
BSL=Baseline. F/U = Follow-Up. BP=Orthostatic Blood Pressure. BMI= Body mass index. 
Telehealth: Participants in this research study may choose to complete appointments via home-based 
telehealth (HBT) care (i.e., service delivery to patients in their homes using consumer-friendly, video-
conferencing technology) which may likely enhance retention by directly circumventing financial and 
transportation barriers associated with traveling to MUSC/VA for in-person sessions. Further, telehealth 
allows the study team to recruit and enroll participants who are located outside of the state of South Carolina 
(inside continental US). HBT sessions will be delivered via standard desk, laptop computer, tablet, or 
smartphone running MUSC/VA approved applications. Participants who choose telehealth will be required 
to have their own computer, tablet, or smartphone; however, webcams will be provided to participants for 
these visits as needed. Participants will be mailed required materials such as alcohol saliva test strips, 
pregnancy tests, and medication. Separate appointments will be made with each partner for instances where 
study team needs to meet with each individual separately or privately.  
Biological samples will not be collected for individuals participating in HBT care, however prior to the 
baseline appointment the study team will mail pregnancy tests and alcohol saliva strips to test for pregnancy 
and recent alcohol use. The alcohol saliva strip must read white (indicative of 0.00 BAC to validate the 
consent and prior to completing any study procedures. Further, prior to proceeding, females will be asked 
to take a pregnancy test and must provide verbal confirmation of a negative pregnancy test prior to 
proceeding with the baseline appointment and prior to administration of any study medication.  
 
Female participants who complete appointments via telehealth will be required to take an at-home urine 
pregnancy test during those visits (provided by study team) and confirm a negative result (verbally and with 
photo of dipstick). The pregnancy tests used in this study are designed for at-home use, come with clear 
and simple instructions. In very rare and highly unlikely circumstances where the participant is unfamiliar 
with how to provide a urine sample or take an at-home pregnancy test, study staff can provide further 
instructions on how to provide a urine sample, how use the dipstick to test, and to differentiate between a 
positive and negative result. Ability and willingness to perform an at-home pregnancy test is required for 
telehealth female participants. 
 
Study medication and other study required study materials will be shipped overnight from research 
pharmacy to participant’s designated location at the agreed upon date using overnight shipping with 
contracted shipping company (FedEx, UPS) and with appropriate ice packs and temperature monitoring 
device as well as a signature requirement at delivery. Regarding all telehealth participants (including out of 


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state): Research participants will be asked to retrieve the study drug from their refrigerator at the beginning 
of each check-in video telehealth session with study staff. Participants will self-administer the medication 
while in view of the study staff on screen. Once medication is administered, participant will be instructed 
to return drug to their refrigerator prior to continuing with the remainder of the appointment.  
 
Optional Neuroimaging Procedures. fMRI scans will be completed with participants and conducted at 
the MUSC Center for Biomedical Imaging (CBI; see Facilities and Resources), which houses a Siemens 3T 
Prisma MRI scanner (Siemens Medical, Erlangen, Germany). Neuroimaging sessions (Figure 5) will last 
approximately 60 minutes each and take place at baseline and week 12. After baseline, personalized imagery 
scripts will be developed for alcohol and neutral cues according to the manualized procedures described by 
Sinha and Tuit147, which are currently being utilized in several of our team’s ongoing federally-funded 
pharmacological trials for AUD. Participants will also develop a relationship conflict cue consistent with 
our past work. The VAS will be administered prior to, during, and after scanning to track perceived craving. 
Participants will be screened for metal using a self-report questionnaire and a handheld metal detector. 
Trained staff will position participants on the scanner bed with foam padding placed around their head to 
prevent motion. Participants will wear headphones to listen to the audio-recorded cues. During initial 
scanner tuning, localizing, and structural scanning, participants will be shown “relaxing” images (i.e., 20 
scenic pictures, each displayed for 30 seconds). For co-registration and normalization of functional images, 
a high resolution T1-weighted MPRAGE anatomical image will be acquired with the following parameters: 
TR = 2300 ms, TE = 2.26 ms, flip angle = 8°, field of view = 256 mm, slice thickness 1.0 mm, 192 slices. 
The scanning planes will be oriented parallel to the anterior commissure–posterior commissure line.  
 Next, participants will be asked to relax and keep their eyes opened and fixed on a cross-hair while 
resting state data are collected across two 7-minute runs. Following this, participants will be exposed to 
alcohol, trauma and neutral cues. We will use a block design consisting of four 2-minute blocks. During the 
alcohol cue block, participants will hear an audio recording describing in detail the last time they consumed 
alcohol. During the trauma cue block, participants will hear an audio recording describing in detail their 
traumatic event. Between the alcohol cue and trauma cue blocks, participants will hear an audio recording 
describing something neutral, such as their typical morning routine. The same excerpt will be used for each 
run. To minimize potential carry-over effects, the scans will be counterbalanced so that half of the 
participants in each treatment arm (e.g., oxytocin or placebo) are exposed to the alcohol cue first and the 
remaining participants in each group are exposed to the relationship conflict cue first. This order will be 
preserved from pre- to post-treatment scanning for each participant. T2*-weighted gradient-echo planar 
images (EPI) will be acquired with the following parameters: TR = 1100 ms, TE = 30 ms, flip angle = 65º, 
matrix 64 x 64, field of view = 192 mm, slice thickness = 3 mm with no gap, multiband factor = 3, with 48 
slices to cover the entire brain. A gradient field map with the same spatial resolution and slices as the EPI 
will be collected to correct for geometric distortions cause by magnetic field inhomogeneity. 
 
Compensation. Each participant will each receive $100 for completion of the baseline assessment visit, up 
to $75 for completion of weekly ABCT sessions (on an escalating scale), and $100 for each follow-up visit. 
Participants who are eligible and choose to complete the neuroimaging component of the study will also 
receive $30 for the script development session and $100 each for the pre-and post-treatment neuroimaging 
scans. Thus, participants who complete all study components may receive $1,100 total. If obstacles of 
transportation prevent participation, the study team will offer bus, taxi, or mileage reimbursement as 
needed. Mileage reimbursement is available for individuals who travel more than 50 miles to Charleston. 
Reimbursement will be provided at the state-approved rate, and will be capped at 100 miles. Compensation 
types may include, but are not limited to: checks, cash, or gift certificates/cards. 
 
 
10.0 Specimen Collection and Banking  


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Urine samples will be collected for pregnancy testing, urine drug screens, and ethyl glucuronide (EtG) 
testing. Blood samples will be collected from participants in this study for examining phosphatidyl ethanol 
(PEth). Blood will be drawn by trained personnel or the MUSC Research Nexus nursing staff and stored 
the MUSC Fast Flow Lab until ready for processing. Only approved study staff will have access to data 
associated with specimens. 
 
11.0 Data Management and Statistical Analysis Plan 
 
General. Baseline clinical and descriptive characteristics will be examined and compared between 
treatment groups using chi-square tests, Fisher’s exact tests, t-tests, or Wilcoxon rank sum tests, as 
appropriate.  Baseline characteristics that are significantly different between treatment groups will be 
included as model covariates.  The primary analysis will focus on end-of-treatment (i.e., the final three 
weeks 
of 
the 
treatment 
phase) 
outcomes 
using 
an 
intent-to-treat 
framework.   
 
Randomization. Both partners in each couple will be randomized to the same drug condition in a one-to-
one manner utilizing a randomized permuted block design. In order to ensure that the treatment groups are 
balanced with respect to alcohol consumption (TLFB), a stratified randomization process will be used. 
 
We plan to use REDCap and VA REDCap for data capture and management. REDCap (Research Electronic 
Data Capture) is a software toolset and workflow methodology for electronic collection and management 
of research and clinical trial data (Harris et al., 2008; Harris et al., 2007). REDCap provides secure, web-
­based flexible applications, including real time validation rules with automated data type and range checks 
at the time of entry. Exports are made available for several statistical packages including SPSS, SAS, 
SATA, R and Microsoft Excel. The system allows the research team to create and engage respondents using 
a variety of notification methods. 
 
REDCap data dictionaries can be distributed for reuse at multiple institutions. A library of data dictionaries 
is made available for standards-­based data collection forms and validated instruments (Obeid et al., 2012). 
The underlying database is hosted in a secure data center at MUSC/VA, a secure environment for data 
systems and servers on campus, and includes redundancy, failover capability, backups and extensive 
security checks. The system has several layers of protection including, user/group account management, 
"Data Access Groups" which allow data to be entered by multiple groups in one database with segmented 
user rights for entered data, audit trails for all changes, queries and reports, and Secure Sockets Layer (SSL) 
encryption. 
 
 
 
Power and Sample Size. This study is powered to detect moderate treatment group differences in percent 
days abstinent (PDA) and percent of days of heavy drinking (PDH), and relationship functioning as 
measured by the TLFB and DAS-7, respectively at end-of-treatment (weeks 9-12). Assuming 2-sided 
hypothesis testing and alpha levels of 0.05, we will have 80% power to detect treatment group differences 
with effect sizes of 0.6 in the presence of 30% attrition (n=70 couples) during the treatment phase. This 
approach is consistent with treatment group differences in PDA (d=0.59) and PDH improvements (d=0.79) 
in a prior ABCT trial (n=102)26, although we recognize that that trial compared individual therapy vs. ABCT 
(not ABCT ± medication).  In that study, PDA increased from 34.98% ± 29.17% to 80.52% ± 27.75% at 
the end of treatment in the ABCT group, and PDH decreased from 56.83% ± 28.87% to 10.52% ± 22.16% 
in the ABCT group. Incorporating an arcsine or other appropriate transformation to account for non-
normality of these metrics will enable us to discern whether oxytocin enhances end of treatment PDA by 
an additional absolute 9% or greater (i.e., to 80.5% in the ABCT+ placebo group vs. 89.5% in the ABCT + 
oxytocin group) and whether oxytocin further decreases PDH by an absolute 6% or greater (i.e., to 10.5% 


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in the in the ABCT+ placebo group vs. 4.5% in the ABCT + oxytocin group). Another prior ABCT trial 
found that DAS-7 scores (21.1 ± 6.7) remain relatively constant throughout treatment27. We will have 80% 
power to detect treatment group differences of 4 units of improvement in DAS-7 scores. 
 
Missing Data. We will examine whether participants who complete treatment differ from those who drop 
out on key variables, and whether variables on which they differ interact with treatment group to affect 
outcome measures. Because participants will be randomized to treatment condition, it is unlikely that 
missing data will produce biased estimates of treatment effect, as observed and unobserved covariates will 
theoretically be balanced across treatment groups. In addition, less than 10% missing data generally has 
little impact on power and does not introduce bias, regardless of the missing data mechanism. If the percent 
missing data are greater than 10%, multiple imputation techniques will be used to examine the influence of 
missing data on our study findings.  If data are missing not at random, propensity score methods will be 
considered for data imputation. In the propensity score method, first the distribution of the missing indicator 
variable given the observed data is modeled to derive a propensity score. Then observations are grouped on 
these propensity scores and an approximate Bayesian bootstrap imputation is applied to each group. 
 
Hypotheses and statistical approaches for testing each are described below. 
 
Hypothesis 1: The ABCT + oxytocin group will demonstrate significantly greater reduction in alcohol 
consumption from baseline to end of treatment as compared to the ABCT + placebo group (PDA and PDH 
measured by TLFB). 
Hypothesis 2: The ABCT + oxytocin group will demonstrate significantly greater improvement in 
relationship functioning (measured by DAS-7) from baseline to end of treatment as compared to the ABCT 
+ placebo group. 
 
To test hypotheses 1 and 2, a general linear modeling (GLM) framework will be used, treating end-of-
treatment (weeks 9-12) PDA, PDH, and DAS-7 scores as dependent variables (in separate models), and 
treating treatment group (ABCT + oxytocin vs. ABCT + placebo) as the primary independent variable. 
Baseline values for PDA, PDH, and DAS-7 will be included as covariates, along with other potentially 
significant baseline characteristics. Since PDA and PDH may exhibit non-Gaussian distributional forms 
and/or zero-inflation, alternative modeling strategies (e.g., arcsine or Box-Cox transformations, two-part 
Hurdle models) may need to be explored. Model fit will be compared by examination of Likelihood Ratio 
chi-square values. If transformations are necessary, back-transformations will be used in conveying the 
model results. Similar modeling strategies will be used for secondary exploratory outcomes (described 
below). 
 
Hypothesis 3a: PFC-AMY functional connectivity after treatment will be greater in participants who 
receive ABCT+ oxytocin compared to those who receive ABCT + placebo. 
Hypothesis 3b: Baseline PFC-AMY functional connectivity in response to alcohol vs. neutral cues will 
predict the magnitude of change in alcohol use (PDA and PDH measured by TLFB in the final 3 weeks of 
treatment). 
Hypothesis 3c: Baseline PFC-AMY functional connectivity in response to relationship conflict vs. neutral 
cues will predict amount of change in relationship functioning (IP DAS-7 scores in the final 3 weeks of 
treatment). 
 
For hypothesis 3, preprocessing and analysis of fMRI data will use FSL v 5.0148. Preprocessing includes 
rigid-body head motion correction of EPI images within a run, high-pass temporal filtering (sigma = 150 
seconds), geometric distortion correction, slice timing correction, spatial filtering (FWHM = 6 mm) and 
registration to the MNI standard brain template. ‘fsl_motion_outliers’ will be used to determine head motion 
outliers which will be used a covariate of no interest in statistical analysis (together with the 6 rigid-body 


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translation and rotation head motion parameters). The primary analysis of fMRI data will use 
psychophysiological interaction (PPI) modeling149 with a seed region defined in the right AMY region from 
the Harvard–Oxford probabilistic structural atlas thresholded at 50%. Time series will be extracted from 
each participant’s right AMY using ‘fslmeants” after warping the AMY mask into each participant’s EPI 
space. This time series will serve as the physiological regressor for each run. The primary psychological 
regressors are based on the alcohol cue blocks in the alcohol run or the conflict cue blocks in the conflict 
run. The interaction between the primary psychological regressor for each run and the physiological 
regressor is the primary variable of interest.  
fMRI analysis: To assess whether corticolimbic connectivity is modulated by oxytocin, the 
parameter estimate from the PPI interaction term will be extracted in the right and left inferior frontal cortex, 
opercular portion (IFC; -47, 18, 6) in each participant. The IFC regions-of-interest (ROI) are based on our 
preliminary study where the right AMY was functionally connected to the left IFC for the conflict cue, 
especially in women. In addition, the right IFC is strongly implicated in behavioral inhibition150 and may 
not be activated to the same degree in participants with AUD151. The parameter estimates from the left and 
right IFC regions in each IP at pre- and post-treatment will be used in statistical analyses testing hypotheses 
1 and 2 (described above). Because the hypothesized ROI may not yield the most robust response, we will 
also conduct a whole-brain, voxel-wise PPI analysis to identify PFC regions that show the greatest change 
in right AMY connectivity as a function of treatment. The voxel-wise PPI analysis will be conducted 
separately for each run (alcohol, conflict) but pre- and post-treatment sessions will be treated as a repeated 
measure. Group-level analyses will be carried out using FLAME 1 (FMRIB's Local Analysis of Mixed 
Effects) to generate z statistical images for each interaction term in each run. The final statistical maps will 
be cluster thresholded at Z=2.33, p = .05) and will indicate which regions show the greatest change in 
connectivity with the right AMY as a function of treatment group.  
 
Exploratory Hypothesis 4: The ABCT + oxytocin group will demonstrate significantly greater 
improvement in frequency of within-session behaviors (i.e., positive, negative, and alcohol change-talk 
behaviors measured by the SSCIT-A133 at sessions 1, 4, 8, and 12) as compared to the ABCT + placebo 
group.  
To test exploratory hypotheses, a nonlinear mixed effects modeling framework will be used, where 
nonlinearity is likely to arise when participants transition from the treatment to follow-up phase. Separate 
models will be constructed for IPs and their partners. Time-specific outcome data will serve as dependent 
variables (in separate models, with treatment group being the primary independent variable of interest.  
Baseline values for PDA, PDH, DAS-7 and sex will be included as covariates, along with other potentially 
significant baseline characteristics. Models will include linear (and possibly non-linear) effects for time 
through the 6-month follow-up, allowing for changes in time effects to occur at end-of-treatment (i.e., using 
a regression ‘join-point’). Random subject effects will be incorporated to account for the fact that within-
subject measurements over time are correlated with each other. Autoregressive covariance structures along 
with other structures (e.g., compound symmetry, spatial power) will be investigated, with final models 
based on Akaike Information Criterion. When examining outcomes involving counts (i.e., positive, 
negative, and alcohol change-talk behaviors), we will assume these variables follow Poisson and/or negative 
binomial distributions, accompanied by log-link functions within a generalized linear mixed models 
framework.   
 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects  
 
Summary of the Protocol. The proposed Stage II study will examine the efficacy of oxytocin in combination 
with a behavioral intervention (ABCT) in reducing alcohol use disorder (AUD) severity and improving 
relationship functioning among couples. We will also examine the ability of oxytocin to modify 
corticolimbic connectivity from pre- to post-treatment. Primary outcomes include AUD symptom severity 


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and intimate partner relationship functioning. Between-group changes in corticolimbic connectivity will also 
be evaluated. 
 
Trial Management. Dr. Flanagan (PI) will be responsible for monitoring the trial. The study will be managed 
from the Addiction Sciences Division within the Department of Psychiatry and Behavioral Sciences at the 
Medical University of South Carolina (MUSC), College of Medicine, Charleston, SC.  
 
Responsible Party. Dr. Flanagan (PI) and Dr. Brady (Co-I and Study Physician) will be responsible for 
distinguishing between serious (SAEs) and non-serious adverse events (AEs), and determining study 
relatedness.  
 
DSM Board. We will create a DSMB to monitor overall participant safety, the rate and severity of adverse 
events, and the validity and integrity of the data. The panel includes 2 researchers with experience in 
treating patients with AUD (Lindsay Squeglia, Ph.D. and Kevin Gray, M.D.) and a biostatistician (Amy 
Wahlquist). The board may be called at any point if needed for unexpected AEs, etc. Modifications will 
be made in the procedures and/or the protocol if necessary based on the recommendations of the 
board. Confidentiality will be maintained during all phases of the study. 
 
Adverse Events. An Adverse Event (AE) is defined as any unwanted change, physically, psychologically or 
behaviorally, that occurs in a study participant during the course of the study that may or may not be related 
to study participation. AEs are reportable to the local Institutional Review Board (IRB) if the AE is 
unexpected AND related or possibly related AND serious or more prevalent than expected. The IRB 
definition of unexpected is that the AE is not identified in nature, severity or frequency in the current protocol, 
informed consent, investigator brochure or with other current risk information. The definition of related is 
that there is a reasonable possibility that the adverse event may have been caused by the drug, device or 
intervention. All AEs will be reviewed weekly by the PI, and annually by the Data and Safety Monitoring 
Board (DSMB), MUSC IRB, and VA Research and Development. A Serious Adverse Event (SAE) is defined 
as an adverse event that has one of the following outcomes: results in death, is life-threatening, requires 
inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant 
disability/incapacity, is a congenital anomaly/birth defect, OR requires intervention to prevent one of the 
above outcomes.  
 
AE/ Unanticipated Problem Follow-up. Unanticipated problems, potential AEs and SAEs will be identified 
during the study via self-report data, as well as weekly assessments and interviews. All unexpected AEs and 
SAEs will be monitored until resolved. A detailed summary of all AEs will be prepared weekly by the research 
staff and reviewed by the PI and Study Physician at the weekly study team meeting. 
 
Risks of Study Participation. Risks of participation related to oxytocin safety, pregnancy, neuroimaging, and 
confidentiality are outlined in the Human Subjects Section. Well-established strategies to protect participants 
from risks are also outlined.  
 
Safety Reporting. All unexpected AEs will be reported to the MUSC IRB and NIH within 10 working days. 
AEs are reportable if the AE is unexpected AND related or possibly related AND serious or more prevalent 
than expected. The IRB definition of unexpected is that the AE is not identified in nature, severity or 
frequency in the current protocol, informed consent, investigator brochure or with other current risk 
information. The definition of related is that there is a reasonable possibility that the adverse event may have 
been caused by the drug, device or intervention. SAEs will be reported within 48 hours of knowledge of the 
SAE. In accordance with the MUSC IRB, any deaths that occur during the study or 30 days post termination 
from the study will be reported within 24 hours, regardless of whether it is expected or unrelated. Follow-up 
of all unexpected and serious AEs will also be reported to the appropriate agencies. All AEs are reviewed 


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weekly by the PI, and annually by the DSMB and IRB. Any significant actions taken by the local IRB and 
protocol changes will be reported to NIAAA. An annual report summarizing all AEs will be provided to the 
NIAAA project officer. This report will include 1) confirmation of adherence to the DSMP, 2) a summary 
of any data and safety monitoring issues that have arisen since the previous report, 3) a description of any 
changes in the study protocol or DSMP that might possibly affect risk, and 4) all new and continuing IRB 
approvals.  
AEs and SAEs occurring during the course of study will be collected, documented, and reported in 
accordance with protocol and IRB reporting requirements. All research staff involved with AE reporting will 
receive training including identification, evaluation, documentation and reporting. All research staff will 
identify any potential AEs during the course of the study from self-report data and administration of 
assessments and interviews. This information will be provided to the PI, who will be responsible for AE/SAE 
assessment and evaluation including a determination of seriousness and study relatedness.  Important 
medical events that may not result in death, be life-threatening or require hospitalization may be considered 
a serious adverse experience when, based upon appropriate medical judgment, they may jeopardize the 
participant and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
When a reportable SAE is identified, research staff will initiate an SAE form, and the following 
individuals will be notified within 48 hours of knowledge of the SAE: study co-investigators, the MUSC 
Institutional Review Board (IRB), the NIAAA project officer, and members of the Data Safety Monitoring 
Board. If complete information is not available when the initial 48-hour SAE report is disseminated, follow-
up information will be gathered to enable a complete assessment and outcome of the event. This information 
may include hospital discharge records, autopsy reports, clinic records, etc. The research staff will attach 
copies of source documents to the SAE report for review by the PI and for forwarding to the NIH project 
officer as appropriate. In addition, the PI will provide a signed, dated SAE summary report, which will be 
sent to the NIAAA Medical Safety Officer within two weeks of the initial SAE report. 
 
Inclusion/Exclusion Criteria.  
 
Inclusion criteria  
1) Male or female; any race or ethnicity; aged 18-75 years. 
2) Able to provide informed consent and function at an intellectual level sufficient to allow accurate 
completion of the assessment instruments (> 26 on the Mini-Mental State Exam). 
3) Married, cohabiting, or in a committed relationship for ≥ 6 months. 
 
4) Identified Patients (IPs) must meet DSM-5 diagnostic criteria for current (i.e., past 12 months) 
alcohol use disorder (assessed via the MINI). Couples in which both partners meet diagnostic criteria 
for current AUD are eligible for participation. 
5) Concurrent substance use disorders (e.g., marijuana) are acceptable provided that alcohol is the IP’s 
primary substance of choice. 
6) Participants taking psychotropic medications will be required to be maintained on a stable dose for 
at least four weeks before study initiation. This is because initiation or change of psychotropic 
medications during the course of the trial may interfere with interpretation of results. 
 
Exclusion criteria 
1) Meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, or with 
current suicidal or homicidal ideation and intent. Those individuals will be referred clinically for 
treatment. 
2) Participants who present a serious suicide risk or are likely to require hospitalization during the study. 
3) Participants on psychotropic medications which have been initiated during the past 4 weeks. They 
may be re-assessed after at least four weeks on a stable dose. 


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4) Acute alcohol withdrawal as indicated by CIWA-Ar scores >8. They may be re-assessed once they 
are no longer in withdrawal. Those individuals will be referred for medically supervised 
detoxification.  
5) Severe unilateral intimate partner violence in the past 6 months as defined by the CTS-2. 
6) Pregnancy or breastfeeding for women. 
7) Individuals with implanted metal devices above the waist will be eligible to enroll in the clinical trial 
but will not be eligible to participate in the neuroimaging component of the study. 
 
Study Safety. Dr. Flanagan (PI) or Dr. Back (Co-I) will be present or on call at the time of all study 
visits. The proposed study does not involve alcohol or drug administration. Females who are pregnant or 
breastfeeding are ineligible to participate due to the known effects of the study drug (oxytocin) on 
parturition and lactation. Couples must agree to use a reliable method of birth control and female 
participants will complete pregnancy tests each week during the treatment phase (for telehealth participants, 
pregnancy tests will be provided and study staff will require a verbal confirmation of negative pregnancy 
test prior to medication administration). If one of the participants becomes pregnant during the trial (despite 
the requirement to use an approved method of contraception), the study staff will continue to follow the 
participant through the course of the pregnancy. Further, since this is an intent-to-treat trial, participants 
will be allowed to continue in engage in therapy offered as part of standard of care in this trial. Participants 
who become pregnant will no longer be allowed to engage in the experimental portion of the trial and the 
study medication will no longer be administered. Additionally, they will not be asked questions or 
administered surveys regarding illegal substance use. Participants who become pregnant will also be 
excluded from completing urine drug screens. Since ABCT is the standard of care for couples where one 
individual meets AUD criteria, continuing to allow both participants to participate in the standard of care 
portion of the trial holds the prospect of direct benefit to the participant and is in the best interest of the 
participant. Protocols for reported AEs and SAEs are outlined above. All unexpected AEs and SAEs will 
be monitored until resolved. A detailed summary of all AEs will be prepared weekly by the research 
staff. At the weekly team meetings (or before if urgent), the research staff will report any premonitory 
symptoms of clinical deterioration. Study procedures will follow the FDA’s Good Clinical Practice 
Guidelines (www.fda.gov/oc/gcp). Any outside requests for information or any breaches in confidentiality 
will be reported to Dr. Flanagan. All requests by participant’s physicians and other medical providers will 
be referred directly to the applicant. 
 
Follow-Up Phase. All participants will be provided with a list of community resources upon study 
completion. Individuals presenting at any time with serious mental or physical health symptoms including 
acute alcohol withdrawal will be referred clinically for treatment. All AEs occurring during the follow-up 
phase will be reported to MUSC IRB and NIAAA. SAEs occurring during the follow-up phase will be 
reported to MUSC IRB and NIAAA within 48 hours. Any participant demonstrating clinical deterioration 
will be referred clinically consistent with the procedures outlined in the Human Subjects section. In the event 
that emergency evaluation or intervention is necessary, the participant will be escorted by a study staff 
member to the psychiatric walk-in clinic or emergency room. Psychiatric hospitalization is available for 
emergencies at any point in the study. 
 
Data Management and Analysis. A data analytic plan (including power calculation) is outlined in the Data 
Analysis section. This study is powered to examine the efficacy of oxytocin versus placebo on the primary 
outcomes of interest. The main outcome variables include the severity of AUD, relationship functioning, 
and corticolimbic connectivity determined via neuroimaging procedures. Analyses will be guided by the 
specific hypotheses of the study and conducted by the study biostatistician, Dr. Paul Nietert. Post-hoc 
exploratory analyses will be conducted with two-tailed tests and more conservative statistical procedures 
which guard against Type I error (e.g., Tukey tests). All primary hypotheses will be tested at level of 


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significance α=0.05. We will also estimate the effect sizes of interest and provide 95% confidence intervals. 
Please see the Statistical Analysis and Power section for more details. 
 
Quality Assurance and Confidentiality. Data quality will be monitored by random inspection of the 
completed forms by research staff and any irregularities or problems detected will be discussed with the PI. 
Project therapists will receive standardized training from the PI and Co-Is (Drs. Flanagan, Back, and 
McCrady). Dr. McCrady developed the ABCT intervention which will be utilized in the proposed study 
and is currently being tested in several federally-funded trials to examine various adaptations of ABCT. 
Adherence to the manual will be monitored using videotapes and weekly supervision. If therapy drift is 
observed the therapists will be re-trained. Booster sessions will be held annually. 
 
DSM Plan Administration. The PI will be primarily responsible for monitoring the study. The PI and a 
statistician will examine the outcomes database for missing data, unexpected distributions or responses, 
and outliers. A DSMB report will be filed with the IRB on a yearly basis, unless greater than expected 
problems occur. The report will include participant characteristics, retention and disposition of study 
participants, quality assurance issues and reports of AEs and SAEs. We will report main outcome results 
at the end of the trial. An annual report of all AEs will be submitted to the NIAAA project officer. In 
addition, all AEs will be reviewed weekly by Dr. Flanagan, and annually by the DSMB, local IRB and VA 
Research and Development. Any significant actions taken by the local IRB and protocol changes will 
be reported to NIAAA.  
For any SAE, the appropriate SAE protocol specific reporting forms will be completed and 
disseminated to the appropriate persons and within the designated timeframes as indicated above. If 
complete information is not available when the initial SAE report is disseminated, follow-up information 
will be gathered to enable a complete assessment and outcome of the event. This information may include 
hospital discharge records, autopsy reports, clinic records, etc. The research staff will attach copies of 
source documents to the SAE report for review by Dr. Flanagan and for forwarding to the NIAAA Program 
Officer. In addition, the PI will provide a signed, dated SAE summary report, which will be sent to the 
NIAAA Medical Safety Officer within 2 weeks of the initial SAE report. Follow-up of all unexpected and 
serious AEs will be reported to all regulatory entities including the local IRB, DSMB, and NIAAA. 
For each AE/SAE recorded, the research staff will follow the AE/SAE until resolution, stabilization, or 
until the subject is no longer in the study. 
 
Stopping Rules for Clinical Trials. The trial will be stopped under any of the following conditions: 1) there 
is clear evidence of harm; 2) there is no likelihood of demonstrating treatment benefit, or 3) there is 
overwhelming evidence of the benefit of treatment. 
 
ClinicalTrials.gov Requirements: In accordance with Public Law 110-85, the proposed trial will be 
registered with ClinicalTrials.gov. Applicable requirements regarding results reporting will be adhered to. 
 
 
13.0 Withdrawal of Subjects  
 
All participants will be screened thoroughly for eligibility following informed consent. The PI may 
discontinue participation at any time if a participant demonstrates or reports significant distress, presents a 
risk of harm to self or others, or is otherwise unable to complete the study.  Participants may withdraw from 
participation at any time during the study procedure. Clinical referrals to community resources will be 
provided to all study participants. 
 
14.0 Risks to Subjects 


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Oxytocin Safety: Oxytocin is a neuropeptide commonly administered intravenously among women 
during childbirth. Risks associated with oxytocin administration have been noted among women given 
intravenous, but not intranasal, oxytocin for its FDA-approved purpose to induce labor and facilitate 
lactation135,136. These risks include seizures, mental disturbances, nausea, vomiting, irregular heartbeat, high 
blood pressure, and unexpected bleeding or contraction of the uterus and have been observed in a small 
number of women99. However, preliminary studies conducted by our group and others indicate that risks of 
intranasal oxytocin administration at the planned dose of 40 IU is minimal and manageable through the 
proposed human participants protection methods. Our group has administered intranasal oxytocin at this 
dose to over 300 research participants to date, including distressed couples with AUD and intimate partner 
violence, without a single adverse event reported. Participants will be informed about the potential side 
effects of oxytocin and will be closely monitored by the research team. Oxytocin self-administration 
will occur only in the context of the study visit with clear instruction from the study staff, who are equipped 
with ready access to clinicians and emergency care if necessary. All participants will be given clear 
instructions on when and where to administer the study medication (only during the study visit, while study 
staff are monitoring). The study medication will be stored in under refrigeration before and after medication 
administration (either at the participant’s home or at the study site).  
All telehealth participants complete a participant locator form with study staff, that allows the study team to 
identify local emergency care facilities and contact information. Specifically, for out of state or remote 
participants, the study staff will compile a list of referrals and emergency contacts to provide to study 
participants ahead of enrollment. 
 
Blood Draw: Participants may experience pain or discomfort, faintness, bruising, or bleeding at the location 
where the blood is drawn. There is also a slight chance of infection as a result of having blood drawn. 
 
Risks of pregnancy: Because this study involves a 50% chance of a study subject receiving active 
medication (i.e., oxytocin) and the effects of oxytocin on pregnancy outcome are well known, pregnant and 
lactating females will be excluded from the trial. We will instruct female participants to use appropriate 
forms of contraception, and participants are required to complete pregnancy tests at baseline and weekly 
during treatment.  
 
Risks related to neuroimaging: Participants will be asked to complete two optional neuroimaging scans 
(functional magnetic resonance imaging; fMRI), which will be conducted at the MUSC Center for 
Biomedical Imaging (CBI), which is located on the MUSC campus. There are very few potential risks from 
fMRI itself. There is no exposure to ionizing radiation and the machine and scanning sequences and 
gradients are approved by the Food and Drug Administration (FDA) for routine clinical use. Individuals 
who are claustrophobic may experience some anxiety during the scanning procedures. Participants may 
experience some loud noises during the scanning procedure and there is a mild risk of hearing damage if 
patients are not given hearing protection. All participants in the study will be given hearing protection. 
Participants may experience psychological discomfort from undergoing the scanning procedure, such as 
boredom and fatigue.  Ferrous objects in the body that are undetected could move during scans. This could 
lead to tissue damage and hemorrhage. These risks are outlined in the informed consent document. In our 
past and ongoing studies utilizing fMRI, we have been able to safely complete imaging procedures without 
undue distress or negative outcomes. This includes research with civilians and Veterans who have current 
AUD.  
 
Confidentiality: All possible efforts to protect participants’ privacy and confidentially will be made 
throughout the course of the study. Participants will be provided with a written informed consent document 
which specifies the risks and confidentiality protections and limits of study procedures. 
 


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Adequacy of Protection against Risks 
 
Recruitment and Informed Consent Procedures. All personnel will be trained in the responsible conduct of 
research. Participants will be recruited from MUSC and VAMC treatment clinics, community settings, and 
ads placed on Craigslist and social media to reach participants in South Carolina and in other states inside 
the continental United States. The screening measure contains questions directly pertaining to the study’s 
inclusion and exclusion criteria. Participants who meet eligibility criteria will be scheduled with research 
staff for a baseline assessment session. In a private room, participants will be provided with a 
description of the nature and requirements of study participation, and asked to read and sign an IRB-
approved consent form prior to beginning any study procedures. Informed consent will be collected by 
the Study Coordinator, trained research assistants, PI, or Co-Is. All study personnel will read and attend 
training sessions in the study protocol conducted by the PI and in coordination with the Co-Is. These 
trainings will include the essential elements of ethical conduct of research so that each member of the 
research staff is well-equipped to provide participants with adequate information prior to their agreeing 
to participate in the study.  
Participants will also be informed that they are not required to make a decision about whether or 
not they choose to participate on that day. Although participants will complete the informed consent 
procedure apart from their partner to ensure each partner’s safety and confidentiality and to minimize 
coercion, all participants will have the opportunity to discuss participation with their partner prior to 
providing informed consent. Participants who are eligible to participate and choose to do so will be 
encouraged to ask any questions they might have about the study. Both the participant and research staff 
member will sign the form.  
The informed consent document will outline 1) the sponsorship of the study; 2) the nature, purpose 
and procedures of the research study; 3) the voluntary nature of participation (i.e., participation is not 
required and can be discontinued at any time; 4) duration of the study; 5) potential risks and discomforts and 
potential benefits of participating; 6) that all information will be kept confidential subject to the provisions 
of state and federal law; 7) compensation; 8) alternative treatments; and 9) telehealth procedures and 
limitations. Participants will be informed that they can discontinue participation in the study at any time and 
that this decision will not influence the care they receive at any MUSC or VAMC clinic. 
 
Assessment Procedures. Some participants may experience distress in response to self-report and interview 
measures pertaining to AUD symptoms or associated areas of functioning such as relationship problems or 
depression. Participants may also experience physical or psychological discomfort during the neuroimaging 
procedures or medication self-administration. However, based on the research team’s past experience and 
available literature the risks involved in the proposed project are minimal and manageable. Nevertheless, 
we have a specific protocol in place to manage participant distress in the event that it arises. This protocol 
is discussed in more detail below. Additionally, all participants will receive an evidence-based behavioral 
intervention (e.g., ABCT) that includes techniques to help reduce distress and anxiety, and improve mood 
(e.g., communication skills, cognitive restructuring). We will also inform participants during the informed 
consent process that they may terminate any assessments, study procedures, or therapy sessions at any point. 
Our past and ongoing research suggests that the measures and methods proposed in this study can be 
implemented without undue psychological distress or exacerbation of symptoms. This experience includes 
numerous federally-funded projects with civilians and Veterans with AUD. 
In the event that a participant becomes distressed secondary to participation, they will be encouraged 
to contact the PI. In addition, they will have access to urgent care services at MUSC and VAMC treatment 
clinics, as well as the VA Crisis Line. Telehealth participants not located in Charleston will be provided 
with urgent care contact information local to them. Any adverse effects noted by any project personnel will 
be immediately reported to the PIs, who will then report these adverse effects in writing to the IRB and NIH 
per protocol (see the Data and Safety Monitoring Plan at the end of this section for more details). The 
research team includes several licensed clinical psychologists and psychiatrists who are equipped to help 


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participants manage distress and to evaluate conditions in which participants need additional assistance. In 
the event that a participant becomes significantly distressed, the PI will contact the participant later that day 
to check-in and the following day to ensure they have received necessary resources, and to assess their 
safety and welfare. If called by participants, the PI will attempt to address all participant concerns and set 
up an alternate referral for counseling for those who desire it from outside the project. 
Every attempt will be made to engage participants for the duration of the 12-session treatment phase. 
Participants will be considered drop-outs from the treatment phase if they fail to attend therapy sessions for 
four consecutive weeks, in spite of attempts by phone, email and mail to engage the participant in treatment. 
All telehealth participants complete a participant locator form prior to each visit, that allows the study team 
to identify local emergency care facilities and contact information. Specifically, for out of state or remote 
participants, the study staff will compile a list of referrals and emergency contacts to provide to study 
participants ahead of enrollment. Participants will be provided with contact information for their local mental 
health clinicians, urgent care, and national suicide prevention lifeline for their use should suicidal ideation 
occur outside of weekly therapy sessions. Should a suicide safety plan be needed based on participant’s BDI 
during either baseline or weekly visits, participants will meet with study therapist to complete the suicide 
safety plan together which will also include resources which are local to the participant. 
A note on VA Crisis Line: the VA Crisis Line can be reached at any time from any location. Study teams 
have been trained on how to connect a veteran with the VA Crisis Line via three-way teleconferencing. 
Once the VA Crisis Line is contacted, they will dispatch necessary care to the veteran in crisis anywhere in 
the United States, and provide follow up services.  
 
 
Study Physician. Kathleen Brady, M.D., Ph.D. will serve as the Study Physician on this project. Dr. Brady 
has extensive experience with NIH-sponsored clinical trials involving individuals with AUD and other 
substance use disorders, as well as comorbid psychiatric conditions. She has ample experience monitoring 
and treating individuals with acute substance-related withdrawal. She will review all adverse events, 
unanticipated problems involving risk to participants or others, serious adverse events, and any participant 
deaths associated with the protocol and provide an unbiased written report of the event within 10 calendar 
days. In addition, the investigative team includes psychologists with ample addiction expertise (Drs. 
Flanagan, Back, Bottonari) who will closely monitor study participants. If at any point a participant 
necessitates medical management, psychiatric consultation or psychiatric hospitalization, they will be 
evaluated and referral to treatment will be provided accordingly. If a participant becomes suicidal, 
emergency psychiatric assessment will be arranged. The participant will be closely monitored until they are 
no longer suicidal or an appropriate care plan is in place. 
 
Alcohol Withdrawal. Participants will be screened for acute alcohol withdrawal at the outset of the study. 
Participants reporting CIWA-Ar scores >8 will be excluded from participation and referred clinically.  
 
Military Personnel. Because some participants may be U.S. military personnel, absolute confidentiality of 
research records cannot be guaranteed. However, all possible efforts will be made to protect the 
confidentiality of participants’ data, except in the event of imminent risk to self or others, or in the event of 
disclosure of child or elder abuse. In the event that confidentiality must be broken to protect the safety of 
participants or others, only the data essential to make an adequate report to authorities will be disclosed. All 
participants will review the IRB-approved informed consent document with research staff in a private room 
separate from their partner. Through this process, research staff will inform all research participants of the 
risks of participation, including emotional distress. In the event that a participant experiences substantial 
distress or reports risk of harm to oneself or others, they will be asked to complete a safety plan. The Mobile 
Crisis Unit of Charleston County and urgent care services on the MUSC campus are additional resources 
available to study staff and research participants. Risks of participation will be outlined in the informed 


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consent and reviewed during the informed consent procedure. In similar past and ongoing studies, these 
resources have been sufficient to manage problems or distress related to participation. 
 
Neuroimaging. All project study staff will be required to complete the CBI’s MRI safety training class. The 
course is taught by an American Registry of Radiologic Technologists registered technician. The staff will 
be trained about safety in the MRI environment, and how to screen oneself and others. The staff will also 
have knowledge of safety procedures for entering the scanner facility, safely removing participants from 
the scanner, when and how to quench the magnet and basic emergency procedures including emergency 
contact information. Standard operating procedures for emergency situations are located on-site. The MRI 
technician and Dr. Joseph (Co-I) are authorized to operate the equipment and will be present throughout 
the scanning sessions.  Although there are no known risks of MRI scanning to a developing fetus at 3.0 T, 
the possibility that risks could be discovered in the future cannot be ignored. Therefore, urine pregnancy 
tests will be used to exclude pregnant women from study participation.  A careful metal screening history 
will be taken from each participant to assess the possibility of metal devices/implants and will be reviewed 
by the PI, MRI technician and/or clinical staff who have had extensive training and experience with MRI 
safety. If the screening yields information that raises a question of safety, the participant will be asked to 
provide the appropriate documentation (i.e., film) before they are allowed to participate. In addition, 
participants will be asked to empty their pockets and will be screened with a hand-held ferromagnetic-
detector wand. Participants will wear earplugs and sound-dampening headphones to decrease the intensity 
of the scanner noise.  Prior exposure to pictures of the scanner, getting into the scanner, and seeing others 
in the scanner, often reduces psychological discomfort or identifies people for whom scanning is not 
appropriate.  
 
Safety and Monitoring Plan. A procedure for clinical deterioration has been established based upon our 
experience with previous and ongoing NIH-funded clinical trials. Therapists (who will be trained Master’s 
or Doctoral level clinicians) will be instructed to use their best clinical judgment regarding emergencies and 
inform the PI as soon as possible. In addition to relying on clinical judgment on the part of the treating 
therapists who are experienced with this population, we will also monitor alcohol and drug use, depression, 
and relationship functioning weekly using standardized measures (TLFB, BDI-II, DAS-7, 
breathalyzer/saliva alcohol tests) in order to detect any symptom worsening requiring further evaluation. 
Additionally, participants will be advised to observe any signs of worsening alcohol use, depression 
symptoms, or relationship functioning including intimate partner violence, and to discuss these challenges 
with their therapist. 
Participants will be withdrawn from the study and referred for more intensive treatment if: (1) there 
are increases in alcohol use leading to the need for a more intensive level of care (i.e., medical 
detoxification, inpatient or partial hospitalization); (2) there is active suicidal or homicidal ideation and/or 
intent; (3) there is an inability to manage the participant psychiatrically within the inclusion/exclusion 
criteria of the study (i.e., need for the initiation of psychotropic medications; development of psychosis); or 
(4) there is an inability to complete ABCT therapy appointments due to incarceration or hospitalization. 
There is a well-established protocol at MUSC for emergency psychiatric evaluation, crisis 
intervention and/or psychiatric hospitalization for suicidal, homicidal, psychotic or other acutely distressed 
participants. Immediately on detection of these needs, the assessor/therapist will page a psychiatrist to 
review the participant's situation. If appropriate, the psychiatrist will personally evaluate the participant. 
Alternatively, during weekdays, the participant will be escorted by a study staff member to the psychiatric 
walk-in clinic or emergency room. Psychiatric hospitalization is available for emergencies. 
Participants will be informed during informed consent procedures of the standard limitations of 
confidentiality such as imminent risk of harm to self or others, or child or elder abuse. Participants will be 
informed that they can decide not to answer any questions and, should they become distressed or are 
uncomfortable with continuing to participate, they may discontinue participation at any time without 
penalty. The compensation schedule will be stated verbally and in writing in the initial study description 


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and the informed consent procedure. The participant’s copy of the consent form will provide contact phone 
numbers and email for the PI should a participant have any questions, comments, or concerns about their 
participation. Participants will have the opportunity to have a copy of the consent form mailed to them at 
any time. 
 
Suicide Specific Risk Identification and Response Plan. Specific precautions will be taken to prevent harm 
to participants and potential participants. Project therapists will be trained Masters or Doctorate level 
clinicians and will be supervised by Dr. Flanagan (PI) and Dr. Back (Co-I), who are licensed clinical 
psychologists. All project therapists and staff will be specifically trained to assess suicide risk, including 
ideation, plan, and intent as well as history of ideation or attempts, and they will be trained to develop a 
safety plan with participants. In initial screening procedures, participants identified by clinical interview 
with both suicidal ideation and acute intent will be excluded from the study, but will be offered emergency 
psychiatric care immediately. This care is available 24 hours per day at MUSC and the Charleston VAMC, 
as indicated above. Moreover, during the course of the study, any participant scoring above 25 on the BDI-
II (administered weekly) or answering a 1 or above to question 9 will be specifically queried about suicidal 
ideation and intent. In any instance where ideation or intent is identified, the PI will be immediately notified 
and will contact the participant for further evaluation. If both ideation and intent are present, the 
aforementioned hospital intervention will be provided. Thus, all assessment points represent suicide risk 
identification, assessment, and intervention opportunities. Study therapists and staff will be specifically 
trained regarding the increased risk of suicide in Veterans with chronic pain and substance use disorders, 
and will receive specific instruction of suicide risk assessment during the initial training workshop. In the 
case of acutely suicidal or distressed veterans participating via telehealth and located outside of our 
immediate geographical location (and the state of South Carolina),the study team will initiate a three-way 
call with the VA Veteran Crisis Line who has the ability to locate the veteran and send emergency help to 
the veteran. 
 
Study Implementation and Data Security. We will take careful precautions to maintain confidentiality for 
all participants, using procedures we have used with similar previous studies: All research personnel will 
attend a required in-service training conducted by PI where the screening, informed consent, and assessment 
protocols will be described. All members of the research team will sign a confidentiality agreement that no 
identifying information of specific individuals will appear in any external documents (e.g., peer-reviewed 
publications, presentations) or in any internal reports.  
All study data related to psychological outcomes (i.e., the participant responses to questionnaires) 
and demographics will not have any unique identifying data attached in any way. All participants will be 
assigned a numerical study identifier to minimize the potential to link identifying information with study 
data. One master list of study participants will be kept separate from all other study data. The master list 
will be destroyed upon study completion; it will be kept separate from all data and will be available only to 
the PI, Study Coordinator, and research assistants. To protect participant confidentiality, all data will be 
maintained in a manner consistent with IRB-approved protocol. Data will be stored in locked filing cabinets 
within a locked office and on MUSC’s encrypted computers and data servers. Access to de-identified study 
data will be limited to named project investigators, the Study Coordinator, NIH audit personnel, MUSC 
IRB audit personnel, and the VAMC Office of Research & Development (R&D) personnel. Data will be 
maintained per an IRB-approved protocol. 
The study protocol and safety plan will be printed and kept in a central location within the research 
space for easy access for all research staff. Standard operating procedures (SOPs) for the management of 
any participant or study-related emergency will be established and research staff will be trained on these 
protocols. At least two members of the study team will be present during all participant appointments in 
order to ensure the safety of participants and research staff. Appointments will be scheduled primarily 
during normal working hours, however accommodations will be made to fit participants’ schedules.  


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All research staff has completed or will complete the University of Miami CITI training course in 
the responsible conduct of research. Necessary certifications in the responsible conduct of research and the 
protection of human research participants will be completed on an annual basis, in compliance with MUSC 
institutional and NIH regulations. 
 
15.0 Potential Benefits to Subjects or Others 
            While there is no guarantee of specific benefit to participants in this study, the potential benefits 
include a thorough psychological and substance use assessment, referral to appropriate treatment services 
and community resources, and remuneration. Participants may also benefit from receiving access to an 
evidence-based behavioral treatment which may result in a reduction in aversive AUD symptom severity, 
improvement in relationship functioning and symptoms of other mental health problems (e.g., depression) 
and improvements in other areas of functioning (e.g., sleep, quality of life). Other study benefits include 
regular contact with research staff, access to assessment information pertaining to mental health, substance 
abuse, etc., and referral to treatments for associated problems such as smoking. While these benefits may 
be considered minimal, we believe that they outweigh the minimal risk and burden incurred by participants. 
Participants will also enroll in a study that has the potential to enhance treatment for other patients and 
families with AUD. 
 
16.0 Sharing of Results with Subjects 
Study data will not be shared with participants to maintain confidentiality. 
 
17.0 Drugs or Devices  
The IND for oxytocin’s use in this study is held by Dr. Flanagan. Oxytocin will be compounded, stored, 
and dispensed by Investigational Drug Services (IDS) on the MUSC campus or Pitt Street Pharmacy in 
Mt. Pleasant, SC. Pitt Street Pharmacy is a compounding pharmacy used by many other MUSC clinical 
trials, including others within our group. Pitt Street Pharmacy is also a member of The International 
Academy of Compounding Pharmacists (IACP). IACP is an international, non-profit association 
protecting and promoting the art and skill of pharmaceutical compounding.  
 
Anjinetta Johnson, PA or Jennifer Jones, MD will send participants’ prescriptions to the Pitt Street 
Pharmacy each week. Pitt Street Pharmacy will assign participants to one of the treatment groups 
(oxytocin or placebo), but this information will remain blinded to the research staff and to the participants. 
Research staff will pick up the weekly prescriptions from Pitt Street Pharmacy and transport the study 
drug to the research site (using a cooler bag with an ice pack to maintain refrigeration). Research staff will 
administer the study drug to participants in our Charleston Center offices. Research staff will select the 
prescribed medication for each individual participant, will confirm the identity of the participant, and will 
instruct participants on the correct method of administration to achieve the desired dose and will observe 
participants’ self-administration. Participants will blow their nose, exhale through their nose, then spray 
into one nostril while inhaling, alternating nostrils until the 40 IU dose is achieved. 
 
CTSA grant acknowledgement: 
This publication [or project] was supported by the South Carolina Clinical & Translational Research 
(SCTR) Institute, with an academic home at the Medical University of South Carolina, through NIH 
Grant Numbers UL1 RR029882 and UL1TR000062. 
 
 
 
 


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ICF_001.pdf: 
Page 1 of 12 
Version Date: 8.16.22 
 
 
 
IRB Number: «ID» 
Date Approved «ApprovalDate» 
 
 
 
 
PROTOCOL TITLE: Oxytocin to Enhance Alcohol Behavioral Couple Therapy  
 
PRINCIPAL INVESTIGATOR: Julianne Flanagan, Ph.D. 
 
ClinicalTrials.gov ID: Pro00082233 
 
Document Date: August 16, 2022 
 
 


Page 2 of 12 
Version Date: 8.16.22 
 
 
 
IRB Number: «ID» 
Date Approved «ApprovalDate» 
 
 
 
Medical University of South Carolina 
CONSENT TO BE A RESEARCH SUBJECT 
 
TITLE OF RESEARCH: Oxytocin to Enhance Alcohol Behavioral Couple Therapy 
 
 
A. PURPOSE OF THE RESEARCH 
You are being asked to volunteer for a research study. Research studies are voluntary 
and include only people who choose to take part. Please read this consent form carefully 
and take your time making you decision. As the study staff discuss this consent form with 
you, please ask him/her to explain any words or information that you do not clearly 
understand. 
 
The purpose of this study is to examine the ability of a medication called oxytocin to 
reduce alcohol consumption and improve relationship functioning during couple’s 
therapy.  Oxytocin is currently approved by the Food and Drug Administration (FDA) to 
induce labor in pregnant women.  However, oxytocin is considered “investigational use” 
Concise Summary 
 
Your consent is being sought for a research study. Participation is voluntary. The 
purpose of the study is to examine if an investigational medication called oxytocin, 
which comes in the form of a nasal spray, is able to improve the outcomes of a talk 
therapy called Alcohol Behavioral Couples Therapy. If you and your partner are eligible 
and you decide to enroll in the study, your participation will last approximately 17 weeks, 
or 9 months.  
 
The study will involve a screening phase which will include 1-2 appointments. You will 
complete questionnaires and interviews in a private room apart from your partner and 
some tests to measure alcohol use and pregnancy. The treatment phase of the study 
will involve 12 weekly therapy visits, which can be performed in person or via home 
based teleheath. Before each therapy session, you and your partner will take the study 
medication or placebo (saline) in the form of a nasal spray. You will also complete 
follow-up visits three months and six months after the treatment phase is complete. 
There are risks of participating in the study that are described in this document.  The 
most significant risks include risks for pregnant women and loss of confidentiality. If you 
are a woman, you will complete a pregnancy test each week before the medication is 
taken to be sure that you are not pregnant. 
 
Everyone who participates will be provided with 12 weeks of an evidence-supported 
talk therapy to help couples reduce problems associated with alcohol use and improve 
their relationship functioning. Your alternative is not to participate in the study. 


Page 3 of 12 
Version Date: 8.16.22 
 
 
 
IRB Number: «ID» 
Date Approved «ApprovalDate» 
 
 
in this study, meaning that the FDA has not approved it for the purpose of improving 
outcomes in couple’s therapy for alcohol use disorder. This is a Phase II study of oxytocin, 
meaning that it has established use for other purposes and researchers are now testing 
this medication in larger populations.  You are being asked to participate because you 
are over 18 years of age, you are in a romantic relationship, and either you or your partner 
has an alcohol use disorder. The investigator in charge of the study is Dr. Julianne 
Flanagan at the Medical University of South Carolina (MUSC).  This study is being 
conducted with funding from a grant from the National Institute on Alcohol Abuse and 
Alcoholism (NIAAA). Portions of Dr. Flanagan’s and her research team’s salaries will be 
paid by this grant. This study is being conducted in Charleston, SC and will involve 
approximately 100 couples, or 200 participants total.  
 
B. PROCEDURES 
If you agree to be in this study, the following will happen: 
1. Screening visit 
a. In total, this study will include approximately 17 visits. The first visit is includes 
screening for study eligibility and will take approximately 3 hours. You have the 
option to complete this in 1 or 2 visits. During that time, you will be asked to answer 
some questions about yourself such as your age, health, relationship with your 
partner, and your use of alcohol and drugs to determine if you are eligible to 
participate.  
b. If you have recently started taking a prescription medication, you may be asked to 
wait 4 weeks until you participate in the study so that the effects of the medication 
will be stable and won’t affect the study results.  
c. If you meet initial eligibility criteria and you choose to participate, you and your 
partner will begin the assessment portion of the screening visit. If you are a woman, 
you will be asked to complete a urine pregnancy test. The urine pregnancy test 
must be negative in order to participate. If your pregnancy test is negative, or if you 
are male, you will be asked to provide a urine sample to test for drug use and a 
marker of recent alcohol use called Ethyl Glucuronide, or EtG.  You will complete a 
breathalyzer test and will undergo a short physical exam. 
d. You will also be asked questions and given questionnaires to complete about your 
use of alcohol, drugs, and tobacco, mood, behaviors, sleep, and thinking abilities. 
e. Trained personnel will take a blood sample to measure levels of a marker of alcohol 
drinking called phosphatidyl ethanol, or PEth. Five total blood samples will be taken 
during the study. Each time, 4mL of blood will be drawn (about a teaspoonful 
amount). 
2. Weekly visits- Treatment Phase 
a. There will be 12 weekly study visits that will last approximately 2-2.5 hours. You 
and your partner will complete weekly visits together and in person or via telehealth. 


Page 4 of 12 
Version Date: 8.16.22 
 
 
 
IRB Number: «ID» 
Date Approved «ApprovalDate» 
 
 
During each visit, you will be asked to complete a pregnancy test prior to 
administration of study medication. If your pregnancy test is negative or if you are 
a man, your urine will may be tested for drug use and EtG.  A breathalyzer or saliva 
alcohol tests will also be done to determine current levels of alcohol in your system. 
After, you will self-administer nasal spray containing either oxytocin or placebo 
(saline). You will also complete a brief check in visit will study staff. Approximately 
30 minutes after the medication is administered, you and your partner will meet with 
the study therapist for your weekly session. A blood draw will be conducted at 
Weeks 6 and 12 in order to test again for PEth. If you are completing this study via 
telehealth, you and your partner will administer the medication at the same time. 
Similar to in-person appointments, study staff will watch the administration of the 
medication.  
b. Each weekly ABCT session will be conducted with a trained therapist, either in 
person or via telehealth. You and your partner will discuss different topics each 
week such as learning about how alcohol use has influenced your relationship, 
managing alcohol cravings, learning how to increase positive interactions with your 
partner, and how to communicate more effectively about alcohol related problems 
and other problems in your relationship. Your therapist will work with you to develop 
practice exercises, or ‘homework,’ that will allow you and your partner to practice 
skills outside of the therapy session.  
3. Follow-up phase  
a. You will also be asked to complete 3 and 6 month follow up appointments – either 
in person or via telehealth. At these visits, you will be asked to complete 
questionnaires and interviews similar to those you completed at the screening visit.  
Much like previous visits, you will answer questions about your overall health and 
wellbeing. Your urine may also be tested for pregnancy, drug use, and EtG. If you 
are completing this appointment in person, a blood draw will be conducted in order 
to test again for PEth. No additional counseling will be provided at these 
appointments. These appointments will last about 1-1.5 hours.  
b.  If there is anything that makes it difficult for you to come to MUSC, you may choose 
to do your study appointments via home-based telehealth (HBT). HBT allows a 
study team member and participant who are not in the same room together to 
communicate. This is usually done over the computer using MUSC approved 
teleconferencing applications. In order to complete sessions via HBT, you will need 
to have internet or cellular access in your home and a computer, tablet, or 
smartphone capable of accessing the internet. Barriers to being unable to come to 
MUSC for face to face treatment varies, but typically involves transportation, 
financial, or child care issues. Biological samples will not be collected for telehealth 
visits. All required study materials will be shipped to you if you complete 
appointments via telehealth (study medication, saliva alcohol test strips, pregnancy 
tests). 


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Version Date: 8.16.22 
 
 
 
IRB Number: «ID» 
Date Approved «ApprovalDate» 
 
 
TELEHEALTH 
If there is anything that makes it difficult for you to come to the MUSC, home-based 
telehealth (HBT) is available for this study. In order to complete sessions via HBT, you 
will need to have internet or cellular access in your home and a computer, tablet, or 
smartphone capable of accessing the internet. If you complete this study via telehealth, 
biological measures and specimens will not be collected. Pregnancy tests, alcohol saliva 
tests, and study medication will be shipped to you monthly via trackable overnight UPS 
shipment. Females will be required to provide verbal and photo (of dipstick) confirmation 
of a negative pregnancy test at each appointment. 
You will be asked to find a private room, away from your partner for portions of the 
baseline visit and for weekly appointments. The study team can also work with you and 
your partner to schedule these portions individually and separately in order to maintain 
protection of your privacy. 
If you and your partner do not live together, medication and study supplies will be shipped 
to one (agreed upon) residence.  
In the event you are unable to make it to the office for your study visit, the study team 
may send you study medication via United Parcel Service (UPS). We would like your 
consent to ship study medication to the address provided on your contact information 
form.  
Please indicate your choice below, or scroll down to the bottom of the screen and select your 
choice electronically: 
 
____Yes, I would like study medication shipped to my residence if I am unable to make 
my appointment, or in the event MUSC is closed.  
____No, I would not like study medication shipped to my residence if I am unable to 
make my appointment, or in the event MUSC is closed.      
C. DURATION 
Participation in the study will take about 17 visits over a period of 9 months.  
 
D. RISKS AND DISCOMFORTS 
Oxytocin: The FDA has approved oxytocin for use among women during labor. When 
used intravenously to start labor, adverse effects associated with oxytocin have included 
seizures, mental disturbances, nausea, vomiting, irregular heartbeat, high blood 
pressure, and unexpected bleeding or contraction of the uterus in a small number of 
women. These side effects have not been observed when oxytocin is used as a nasal 
spray.  However, other side effects may include nasal irritation, runny nose, and tearing 
of the eyes. Several studies have been conducted in humans with intranasal doses similar 
to what will be used in this study, and no adverse side effects have been reported.  
 


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Version Date: 8.16.22 
 
 
 
IRB Number: «ID» 
Date Approved «ApprovalDate» 
 
 
A recent review of the safety and side effects of intranasal oxytocin demonstrate that it 
has been used in over 40 completed randomized controlled trials, with over 1,500 human 
participants. No adverse side effects or outcomes have been reliably observed in children, 
women, or men using a dose of 18-40 IU. Dr. Flanagan’s research team has used a 40 
IU dose of intranasal oxytocin in over 300 research participants to date with no adverse 
side effects. 
 
Risks of  Pregnancy: Because  this  study  involves  a  50%  chance  of  a  study  participant  
receiving  the investigational medication (e.g., oxytocin)  and  it is well known that 
intranasal oxytocin is likely to have negative effects on pregnancy and fetal health,  
pregnant and  breastfeeding  women will  be  excluded  from  the  trial.  We will instruct 
women participants to use appropriate forms of contraception, and you will be asked to 
complete urine pregnancy tests at baseline and weekly during treatment. For telehealth 
participants, study staff will require a verbal confirmation of the negative pregnancy test 
prior to allowing medication administration. If you become pregnant during the trial 
(despite the requirement to use an approved method of contraception), you will be given 
the opportunity to continue to participate in the therapy portion of the study. However, due 
to safety risks, you will no longer be allowed to administer the medication. Additionally, 
you will not be asked questions or administered surveys regarding illegal substance use, 
and you will no longer complete urine drug screens. 
 
Potential Risks of Blood Draw: Risks associated with drawing blood from your arm include 
momentary discomfort and/or bruising. Infection, excess bleeding, clotting, or fainting is 
possible, although unlikely. 
 
Randomization Risk: You will be assigned to the study medication by chance. The study 
medication you receive may prove to be less effective or to have more side effects than 
the other study medication or other available treatments. 
 
Placebo Risk: If you are in the group that receives placebo (saline), your or your partner’s 
condition will go without active medication treatment for 12 weeks. However, everyone 
who participates in the study will receive weekly couple’s therapy with a trained therapist. 
 
Interviews and Surveys: The questions that will be asked may be sensitive in nature and 
may make you feel uncomfortable.  You may be asked personal questions that you find 
distressing. You may refuse to answer any question(s) that you do not wish to answer.  
 
Risk of Loss of Confidentiality  
There is a chance that your personal information may inadvertently not be kept 
confidential. Some answers you give during the research visits (like whether you use 
illegal drugs) may put you at risk if other people find out. To keep what you say private, 
your study records will use a code number instead of your name. We will protect your 
records to the extent allowed by law by keeping all your materials in locked file cabinets 
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files only accessed by research staff. Your research records are kept separate from your 
clinic records and will not be shared with your clinical counselor. Only research staff will 
have access to your private information.  
 
Limits of Confidentiality:  
  
Suspected or known abuse or neglect of a child, disabled or elder abuse, or threatened 
violence to self or others may be reported to appropriate authorities. 
 
If you are or become pregnant and test positive for illegal drugs, it is a law that the South 
Carolina Department of Social Services (DSS) must be notified. You and your family will 
be evaluated by the agency. You could be ordered to mandatory drug treatment, lose 
custody of your children, or possibly be jailed.  
 
Unknown Risks: The experimental treatments may have unknown side effects. The 
researchers will let you know if they learn anything during the course of the study that 
might make you change your mind about participating in the study.  
 
E.  MEDICAL RECORDS AND CERITFICATE OF CONFIDENTIALITY 
 
This research is covered by a Certificate of Confidentiality from the Federal government. 
This means that the researchers may not disclose information or biospecimens that may 
identify you, even by a court subpoena, in any federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings, nor can the information or biospecimens 
be used as evidence, unless you have consented to this disclosure.  Information or 
biospecimens protected by this Certificate cannot be disclosed to anyone else who is not 
connected with the research unless you have consented to the disclosure.  More 
specifically, identifiable information or biospecimens will not  be shared with your medical 
providers who are not involved in this research unless you authorize the study to disclose 
information to them, or if it is used for other scientific research, as allowed by federal 
regulations protecting research subjects.  
 
Information about your study participation will not be in your MUSC medical record.  This 
means that neither your research participation nor any of your research results will be 
included in any MUSC medical record.  A Certificate of Confidentiality does not prevent 
you from voluntarily releasing information about yourself or your involvement in this 
research. If you want your research information released to an insurer, medical care 
provider, or any other person not connected with the research, you must authorize the 
researchers to release it. 
 
The Certificate of Confidentiality will not be used to prevent disclosure as required by 
federal, state, or local law. Examples of required disclosure include: child abuse and 
neglect, or harm to self and others, but there could be others. 
 


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Finally, a Certificate may not be used to withhold information from the Federal 
government needed for auditing or evaluating federally funded projects or information 
needed by the FDA. 
 
F. BENEFITS 
No specific benefit can be guaranteed or promised from participation in this study. 
Information gained from this study may help other researchers have a better 
understanding of the treatment of alcohol use disorder and relationship behaviors.  
 
G. COSTS  
There will be no cost to you as a result of participation in this study.  
H. PAYMENT TO PARTICIPANTS 
 
Each participant will each receive up to $125 for completion of the baseline assessment 
visit, up to $75 for completion of weekly ABCT sessions (on an escalating scale), and 
$100 for each follow-up visit.  Thus, participants who complete all study components may 
receive $895 total.  
 
You will receive payment in the form of a ClinCard, a pre-paid debit card. It works like 
a bank debit card, and you may use the card to purchase goods or services 
everywhere Debit MasterCard is accepted. Should you choose this payment option, 
you will be given a ClinCard at the beginning of the study. Each time you receive 
payment for participation in this study, the money will be added to the card, as outlined 
in the payment schedule above. Compensation may also be provided in the form of 
cash or check. If you receive compensation in the form of check, you will be asked to 
fill out a W9. Payment can also be made via cash, check, or direct deposit. 
 
Finally, if there are obstacles to participation due to transportation, taxi, bus pass, or 
mileage compensation may be available. Mileage reimbursement is available for 
individuals who travel more than 50 miles to Charleston. Reimbursement will be provided 
at the state-approved rate and will be capped at 100 miles. 
 
You are invited to participate in the recruitment of other subjects for this study.  If you 
choose to participate, we will provide you with cards that you may give to other people 
(e.g., friends, acquaintances) who you think would be eligible and interested in this 
study. You may choose to tell people to whom you give these cards to call the study office 
if they are interested in participating in the study.  These individuals will not be identified 
unless they contact the study office themselves.  If any of the cards you are given result 
in successful study recruitment, you will receive $10 for each referred individual who 
consents to participate in the study. Participation in the recruitment process is completely 
voluntary and if you elect not to participate, your participation in this study will not be 
affected in any way. 


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Payments that you receive from MUSC for participating in a research study are 
considered taxable income per IRS regulations.  Payment types may include, but are not 
limited to: checks, cash, gift certificates/cards, personal property, and other items of 
value.  If the total amount of payment you receive from MUSC reaches or exceeds 
$600.00 in a calendar year, you will be issued a Form 1099. 
I. ALTERNATIVES 
This study involves an investigational medication and couples counseling. You have the 
option of declining to participate in this study. Alternative treatments for alcohol use 
disorder and couples counseling are available.  
Withdrawal from the Study 
Your participation in this study is voluntary. You may refuse to take part in or stop taking 
part in this study at any time. You should talk with the investigator in charge of this study 
if you decide to do this. Your decision not to take part in the study will not affect your 
current or future medical care or any benefits to which you are entitled. The investigators 
and/or the sponsor may stop your participation in this study at any time if they decide it is 
in your best interest. They may also do this if you do not follow the investigator’s 
instructions. If your participation is ended for medical reasons, you will be referred to a 
doctor or other health professional for care. You will be responsible for the cost of these 
services. 
J.  DATA SHARING  
Information about you (including your identifiable private information and/or any 
identifiable biospecimens) may have all of your identifiers removed and used for future 
research studies or distributed to other researchers for future research without additional 
informed consent from you or your legally authorized representative. 
K. DISCLOSURE OF RESULTS 
 
Study data will not be shared with participants to maintain confidentiality.  
 
L. SIGNIFICANT NEW FINDINGS 
 
If there are significant new findings during the course of the study, you will be notified.  
 
M. STUDENT PARTICIPATION 
 
Your participation or discontinuance will not constitute an element of your academic 
performance, nor will it be a part of your academic record at this Institution. 
 


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N. EMPLOYEE PARTICIPATION 
 
Your participation or discontinuance will not constitute an element of your job 
performance or evaluation, nor will it be a part of your personnel record at this 
Institution. 
 
O.CLINICAL TRIALS.GOV  
 
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. 
P. COLLECTION OF SPECIMENS 
 
Blood and urine specimens will be collected in this study. We will collect specimens in 
order to measure two biomarkers of alcohol use: urine for Ethyl Glucuronide, or EtG, and 
blood for phosphatidyl ethanol, or PEth. If you are a woman, you will provide a urine 
sample at the screening visit and at each weekly visit during the treatment phase for 
pregnancy tests. If you are not pregnant, all participants will provide a urine sample during 
the screening phase and at each weekly visit in order to conduct a urine drug screen. 
Blood will be drawn by a trained member of the research staff. These specimens will be 
used solely as part of this research study and will not be shared with other investigators. 
All specimens will be coded with your numeric study code to protect your confidentiality. 
 
Q.PERMISSION TO RECORD SESSIONS__________________________________ 
 
We would like to record the therapy sessions to assure treatment quality and adherence 
to the treatment manual. Recording the sessions is not required for participation, but is 
very useful to us. This could pose a risk to confidentiality and although we will take every 
step possible to ensure that all recordings are stored securely and any risks minimized, 
there is a risk is that you could be identified, including information regarding alcohol and 
drug use, or other criminal behavior. To minimize any risk, all recordings will be kept in a 
locked file cabinet or on a secure and encrypted server and only the project staff and 
supervisors will have access to the recordings. They will be destroyed after the study has 
been completed. Would that be acceptable to you?   
 
Please indicate you choice below, or scroll to the bottom of the screen to select your 
choice electronically: 
 
_____ Yes, I permit audio or visual recording of my therapy sessions. 
 
_____ No, I do not permit audio or visual recording of my therapy sessions. 


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R. FUTURE CONTACT_________________________________________________             
The researcher in charge of this study might like to contact you in the future about other 
research opportunities. Please indicate your choice below, or scroll down to the bottom of 
the screen and select your choice electronically::  
____Yes, I agree to be contacted  
____No, I do not agree to be contacted  
You have the option of receiving appointment reminders and link to study surveys through 
text messages.  Should you elect to receive text messages, normal cellular data usage 
and rates will apply. Please indicate your choice below, or scroll down to the bottom of the 
screen and select your choice electronically:: 
____Yes, I agree to be contacted via text message 
____No, I do not agree to be contacted via text message 
 
S. RELEASE OF MEDICAL RECORDS TO ANYONE OTHER THAN THE 
INVESTIGATORS 
 
If for any reason you would like your study records released to anyone other than the 
investigators, you will be asked to sign an additional release of information form. You will also 
be asked to sign a Health Insurance Portability and Accountability Act (HIPAA) Authorization 
to use or disclose your protected health information for research purposes.  
 
CONSENT 
 
Results of this research will be used for the purposes described in this study. This 
information may be published, but you will not be identified. Information that is obtained 
concerning this research that can be identified with you will remain confidential to the 
extent possible within State and Federal law. The sponsor and the Food and Drug 
Administration (FDA) will receive copies of the research records. The investigators 
associated with this study, the FDA, and the MUSC Institutional Review Board for Human 
Research will have access to identifying information. All records in South Carolina are 
subject to subpoena by a court of law.  
 
In the event of a study related injury, you should immediately go to the emergency room 
of the Medical University Hospital, or in case of an emergency go to the nearest hospital, 
and tell the physician on call that you are in a research study. They will call your study 
doctor who will make arrangements for your treatment. If the study sponsor does not pay 
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treatment to you will bill your insurance company. If your insurance company denies 
coverage or insurance is not available, you will be responsible for payment for all services 
rendered to you.  
Your participation in this study is voluntary. You may refuse to take part in or stop taking 
part in this study at any time. You should call the investigator in charge of this study if you 
decide to do this. Your decision not to take part in the study will not affect your current or 
future medical care or any benefits to which you are entitled. 
The investigators and/or the sponsor may stop your participation in this study at any 
time if they decide it is in your best interest. They may also do this if you do not follow 
the investigator’s instructions. 
 
Volunteer’s Statement 
 
I have been given a chance to ask questions about this research study. These questions 
have been answered to my satisfaction. If I have any more questions about my 
participation in this study or study related injury, I may contact Dr. Julianne Flanagan at 
(843) 792-5569. I may contact the Medical University of SC Hospital Medical Director 
(843) 792-9537 concerning medical treatment.  
 
If I have any questions, problems, or concerns, desire further information, or wish to offer 
input, I may contact the Medical University of SC Institutional Review Board for Human 
Research IRB Manager or the Office of Research Integrity Director at (843) 792-4148. 
This includes any questions about my rights as a research subject in this study.  
 
I agree to participate in this study. I have been given a copy of this form for my own records. 
Please sign below for paper consents or scroll to the bottom of the screen to provide an 
electronic signature. 
 
________________________________________     
Signature of Participant                                Date   
 
________________________________________     
 
Signature of Person Obtaining Consent       Date