Clinical trial NCT05207436
Conditions: Post Traumatic Stress Disorder Relational Problems
Keywords: Post Traumatic Stress Disorder Oxytocin Marital Therapy Couples Veterans Telemedicine
Sponsor: San Diego Veterans Healthcare System
Start date: 2022-01-17; Completion date: 2022-12-31
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
In 2019 VA mandated that all Veterans seeking mental health care have access to flexible family mental health services in VA (VHA directive 1163.04). This study aims to respond to this mandate by further improving an evidence-based PTSD treatment designed to decrease PTSD symptoms and improve relationship satisfaction for Veterans and their romantic partners. Brief Cognitive-Behavioral Conjoint Therapy (B-CBCT), an 8-session dyadic psychotherapy for PTSD, has been found to significantly reduce PTSD symptoms, but the effects of B-CBCT on relationship satisfaction are less reliable and robust. Pharmacological augmentation of psychotherapy utilizing intranasal oxytocin, a neurohormone that influences mechanisms of trauma recovery and social behavior, may help improve relationship satisfaction outcomes. If successful, the proposed study will advance knowledge of strategies for improving Veterans' quality of life by improving their intimate relationships along with PTSD symptoms.

Detailed description:
Military Veterans often experience challenges reintegrating into their communities after military service, due in part to mental health problems such as posttraumatic stress disorder (PTSD). PTSD, a psychiatric disorder that develops in response to exposure to traumatic events, disproportionately affects Veterans, leads to poorer physical health, and impairs psychosocial functioning and quality of life. Mitigating the negative effects of PTSD on Veterans' health, functioning, and well-being is therefore a major goal of the VA.

The premise that interpersonal relationships play a key role in resilience, risk, and recovery from trauma is supported by research showing a robust association between PTSD and social support. Treatment approaches that bolster Veterans' internal strengths and enhance the capacity of their social environments to provide support are most likely to have powerful effects on well-being.

Many Service Members and Veterans with PTSD experience impairment and distress within intimate relationships at greater levels than among civilian couples. Consistent with this, Veterans seeking treatment for PTSD often identify relationships as targets of intervention and express the desire to involve close others in treatment. The VA has been responsive to these needs, as shown by the continuum of services available to Veterans and their families through the VA Family Services program. The Veterans' Mental Health and Other Care Improvements Act of 2008 stated that marriage and family counseling were to be available to Veterans to facilitate their treatment and rehabilitation. In 2009, VA began an initiative to select evidence-based family therapies and train mental health providers in these treatments. More recently, Directive 1163.04 indicated that Veterans with a mental health diagnosis should be asked about their interest in having family involved in their care and be offered marital and family counseling. The VA Family Services program supports several treatment approaches to meet the diverse mental health needs of Veterans and their loved ones. One such option for Veterans who want to simultaneously improve their PTSD symptoms and their relationship functioning is Cognitive-Behavioral Conjoint Therapy (CBCT) for PTSD. The VA has been disseminating CBCT since 2013.

CBCT is a PTSD-specific cognitive-behavioral psychotherapy attended by the couple that uses close relationships as the vehicle for recovery. Across 15 75-minute sessions, this manualized therapy addresses the patient's PTSD and relationship functioning simultaneously via its focus on PTSD psychoeducation within relationship contexts, communication skills, behavioral approach exercises, and cognitive interventions. CBCT effectively treats PTSD, exhibiting large within-group effect sizes on clinician-rated PTSD symptoms.

Across studies, however, CBCT has had less robust, more variable effects on relationship satisfaction than on PTSD. This is likely because the factors governing relationship satisfaction are complex and rely on a number of independent, interpersonal factors. The largest published study of CBCT (N = 40 dyads), in which CBCT was compared to a waitlist control group, found a moderate within-group effect (g = 0.64) and between-group effect (g = 0.47) of CBCT on Veterans' relationship satisfaction. This sample, however, was composed of only about 25% Veterans. Given that Veteran couples are known to have lower relationship satisfaction than non-Veteran couples, it is important to further examine CBCT among Veteran couples that are more representative of couples seen in general VA practice to increase generalizability of findings. However, preliminary data from couples treated as part of VA's dissemination of CBCT suggest that effects on relationship satisfaction are noticeably smaller than in previous studies. This may be due, in part, to poor engagement in the intervention. Couples experience many logistical obstacles to engaging in care (e.g., the need to coordinate schedules, lack of childcare). Veterans with PTSD can encounter additional obstacles related to beliefs about mental health and mental health treatment.

To address these obstacles to treatment engagement, Dr. Leslie Morland (PI) recently completed a study of an 8-session version of CBCT (B-CBCT) delivered either in-office or via telehealth to home compared to a family education control condition. She and her team similarly found robust reductions in PTSD symptoms in B-CBCT (B-CBCT within-group d's = 1.05-1.12, between-group d's = 0.59-0.76) but only a small effect on both partners' relationship satisfaction that was on par with the family education condition (B-CBCT within-group d = 0.38; between-group d's = 0.04-0.12).

Medications that potentiate the mechanisms of action in psychotherapy could enhance their effects. The neuropeptide oxytocin appears to be a promising medication because it mediates processes central to PTSD and relationship functioning. Oxytocin is a 9-amino-acid nonapeptide hormone produced by the paraventricular and supraoptic nuclei of the hypothalamus that regulates human emotions, social cognition, and social behaviors. Endogenous oxytocin assists in milk production for breastfeeding, induces contractions during childbirth, is released during orgasm, may reduce urine volume, and may induce sodium release from the kidneys. Intravenous oxytocin is used in medical practice to induce labor in pregnant women and to increase muscle tone in the uterus in the case of postpartum bleeding. Oxytocin is released to several brain areas, including the amygdala, hypothalamus, hippocampus, insula, and striatum, and effects are mediated by oxytocin receptors found in these regions.

Intranasal administration of oxytocin may offer understanding of the causal effects of oxytocin on human behavior. Intranasal oxytocin is safe and easy to administer, with a short half-life that makes it highly suitable for adding to behavioral interventions. Intranasal oxytocin is best known for its widespread effects on affiliative processes and behaviors. For example, intranasal oxytocin increases trust, empathy, generosity, positive communication, and emotional disclosure. Oxytocin also improves social cognition, including emotion recognition and empathic accuracy. The combination of intranasal oxytocin with provision of social support suppresses cortisol release and subjective responses to social stress.

Intranasal oxytocin can be conceptualized as a "psychotherapy process catalyst", in that oxytocin could enhance patients' openness to intervention, attention to others' communication, and willingness and ability to develop therapeutic alliance. A recent systematic review of 14 studies of the effects of intranasal oxytocin on PTSD symptoms concluded that there is tentative evidence for the clinical utility of intranasal oxytocin for PTSD, although more studies with chronic administration are needed. To date, only one pilot study has examined the effects of oxytocin-enhanced psychotherapy for PTSD. Findings indicated that participants randomized to Prolonged Exposure (PE) for PTSD augmented with oxytocin demonstrated lower PTSD and depression symptoms and had higher working alliance scores compared to participants randomized to PE with placebo. A large, two-site phase II randomized controlled trial (RCT) of oxytocin-enhanced PE is currently being conducted in the VA by a Collaborator on this project (PI: Dr. Julianne Flanagan; NCT04228289).

Administering intranasal oxytocin in a safe, therapeutic context in which interpersonal skill-building takes place is hypothesized to lead to prosocial effects and facilitated recovery. CBCT is therefore the ideal treatment platform for oxytocin augmentation. CBCT and oxytocin are both inherently interpersonal and could operate in a coordinated, synergistic manner to improve relationship satisfaction. For example, facilitating positive communication could enhance all aspects of the therapy, including both partners' sharing of thoughts and feelings and their ability to join together in cognitive restructuring of trauma-related beliefs that interfere with recovery. Findings that intranasal oxytocin increases neural activation to socially rewarding stimuli and facilitates social approach behavior suggest that it could help Veterans and their partners embrace social situations, which is central to CBCT behavioral interventions. Lastly, generalization of improvements in trust, empathy, positive communication, and approach behavior could help Veterans participate more fully with their families (e.g., improved parenting skills) and many other domains of society (e.g., education and employment). To date, however, oxytocin has not been tested as an adjuvant to CBCT nor any relationship-focused therapy for trauma-exposed Veterans.

Based on compelling pre-clinical data implicating the oxytocin system in affiliative behavior, the study of intranasal oxytocin in humans expanded very rapidly. However, these developments were followed by calls for caution after acknowledgment of lack of replicability of findings, methodological limitations such as low statistical power, and poor understanding of the pharmacodynamics of intranasal delivery of synthetic oxytocin. Intranasal oxytocin is thought to exert effects by bypassing the blood-brain barrier and reaching the brain directly (i.e., nose-to-brain transport), but definitive data have been lacking. More recently, pre-clinical, primate, and human research have converged to indicate that intranasal oxytocin does, in fact, reach the brain to a degree that leads to clinically relevant changes in behavior, ostensibly through olfactory and trigeminal nerve fibers. Another issue that has affected the translation of oxytocin research to treatment has been the lack of dose-ranging studies in humans. Notably, most intranasal oxytocin studies have administered only one dose of intranasal oxytocin, typically 24 or 40 international units. The pharmacodynamics of repeated oxytocin administration are not well-established, but given the short half-life of intranasal oxytocin (i.e., 20 or more minutes in cerebrospinal fluid and 2 minutes in blood), repeated dosing (e.g., daily, weekly) is not hypothesized to operate differently than single doses.

The proposed study to augment CBCT with intranasal oxytocin and to examine its effects on intimate relationship adjustment, social functioning more generally, and quality of life directly addresses the mission of the VA, as outlined in the VA fiscal year (FY) 2018-2024 Strategic Plan. Specifically, the proposed study seeks to advance knowledge of how to help Veterans have good quality of life-which the VA identifies as including satisfying relationships-in three ways: First, findings will inform whether B-CBCT social functioning outcomes can be improved with adjunctive medication. Second, if oxytocin enhances the mechanisms described in this proposal as predicted, it could further strengthen rationale for providers administering eight-session B-CBCT rather than 15-session CBCT. Effectively truncating CBCT would mean that more patients could be seen by the same number of VA providers, potentially improving Veterans' access to treatment. Greater effectiveness and efficiency of treatment could lead to lower costs to VA. Third, by targeting mechanisms that are salient to all interpersonal relationships (e.g., trust), oxytocin could help the effects of CBCT extend to non-intimate relationships, thereby improving overall quality of life and potentially having effects on other issues facing the VA (such as suicide) which is known to be related to interpersonal difficulties. Lastly, improving Veterans' social environments could help them maintain their gains and respond effectively to future stressors-potentially lowering the likelihood of future need for episodes of care.

Arms: arm 1: Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (B-CBCT) weekly. Prior to each session, the Veteran participant will self-administer intranasal oxytocin. The estimated length of treatment participation is 8 to 15 weeks. All procedures take place in the Veterans home via home-based clinical video teleconferencing (CVT).
Interventions: intervention 1: Oxytocin nasal spray intervention 2: Brief Cognitive-Behavioral Conjoint Therapy
Intervention descriptions: intervention 1: Veteran participants will self-administer 40 IU of intranasal oxytocin 30 minutes before the start of each B-CBCT session. intervention 2: Eight sessions of standardized B-CBCT, a manualized couple-based intervention for PTSD designed to simultaneously reduce PTSD and enhance relationship and functioning.

Protocol documents:
Prot_002.pdf: 
Human Protocol (Version 1.8)
General Information
*Please enter the full title of your protocol::
Pilot Test of Intranasal Oxytocin as an Enhancer of Brief Couples Therapy for PTSD
*Please provide a short name (nickname) to reference this protocol::
CBCT + OT
* This field allows you to enter an abbreviated version of the Protocol Title to quickly identify
this protocol.
Add departments
and Specify Research Location:
Is 
Primary? Site Name
VASDHS - VASDHS
Identify protocol staff members
*Please add a Principal Investigator for the study:
Morland, Leslie A., PsyD
3.1 Add all other VA research staff personnel (if name is not in the list, please contact Research 
Staffing to confirm appointment status)
A) Additional Investigators
B) Research Support Staff
Borigini, Mark, (ORO) 
Auditor
Chargin, Bette 
Research Associate
Galvan, Rachel, (ORO) 
Auditor
Grubbs, Lauren Maiko 
Clinical Research Associate
Hoang, Amy 
Clinical Research Associate
Holcomb, Julie M. 
Research Associate
NCT05207436
9/1/2022
N


Kerenyi, Cynthia, (ORO) 
 Auditor
Khalifian, Chandra E., PhD 
 Post-Doc
Knopp, Kayla C., PhD 
 Post-Doc
Lin, Alex 
 Clinical Research Associate
Maglione, Jeanne E., MD, PhD 
 Participating Clinician
Moxey, Monique, (ORO) 
 Auditor
Rashkovsky, Katerine T. 
 Research Associate
Schnitzer, Janina S., BA 
 Research Associate
Sohn, Min Ji 
 Data Manager
Wachsman, Tamara 
 Research Associate
Webster, Katelyn D., MA 
 Study Coordinator
*Please select the Research Contact(s)
 
Morland, Leslie A., PsyD 
Webster, Katelyn D., MA 
The Research Contact(s) will receive all important system notifications along with the Principal 
Investigator. (Research Contacts are typically Study Coordinators or the Principal Investigator 
themselves).
 
VASDHS IRB
Human Subjects Protocol
v20190121
Section 1 - Preliminaries
Principal Investigator:
Leslie A. Morland, PsyD
Protocol Title:
Pilot Test of Intranasal Oxytocin as an Enhancer of Brief Couples Therapy for PTSD
IRB Protocol Number:
H210143
Protocol Nickname:
CBCT + OT
Form Template Version:
v20150115
Date Prepared:
09/01/2022


Please be advised that this protocol application form has changed as a result of the 2018 Common 
Rule.  There are new questions and sections, and you may be required to provide additional information to 
previous sections.
1a) Is this study considered human research?
Yes 
No 
I don't know 
1b) Please select:
This is an application for a NEW human subject research protocol 
This is a revision of an existing protocol 
 Section 2 - Research Subjects
 
2a) What is the total planned number of VA-consented subjects?
Include the total number of subjects who will prospectively agree to participate in the study (e.g., documented 
consent, oral consent, or other).
40
 
2b) What is the total number of VA subjects who WILL NOT be consented?
Include the total number of subjects that will be included without consent (e.g., chart review).  Note: Data about 
people are still considered “human subjects” by the IRB, so even if you do not intend to contact the patients 
whose charts you will review, you still should enter the number of charts as your “planned subjects."
0
 Section 2.1 Consented Subject Groups
2.1) For each of the subject categories listed below, indicate whether or not these subject groups will 
participate in the study: 
2.1a) Children under the age of 18
Note:   If neonates or children will be involved in this study, certification by the Medical Center Director will be 
required. Only minimal risk research may be performed with children.  Only non-invasive monitoring and/or 
prospective observational and retrospective record review studies that are minimal risk can be conducted in VA 
involving neonates.
  Yes  
  No
2.1b) Pregnant women
  Yes  
  No
2.1c) Individuals with cognitive/decisional impairment
  Yes  
  No
2.1d) Non-English-speaking individuals
  Yes  
  No
2.1e) Prisoners of War (explicitly targeting this group)
  Yes  
  No


2.1f) Non-Veterans (Note: Justification for inclusion of non-Veterans will be required)
 Yes  
 No
2.1g) Incarcerated individuals (Note: VA CRADO approval will be required)
  Yes  
  No
2.1h) VA employees - including VA paid, IPA, or WOC (Note: Union review and authorization may be 
required)
  Yes  
  No
2.1i) Students of the institution (e.g., resident trainees) or of the investigator
  Yes  
  No
2.1j) Patients with cancer (or high cancer risk) [explicitly targeting this group]
  Yes  
  No
 Section 3 - Study Features   (these items default to "No" for convenience)
  
3) This section consists of several Yes/No questions addressing protocol characteristics.     Click on Save and 
.
Continue
 Section 3.1 Protocol Basics
Select all that apply
3.1a) The research 
 the participant.
intends to change
 Yes  
 No
3.1b) 
 with living participants to collect data or specimens with no intent to change them.
Interactions
  Yes  
  No
3.1c) This is a study that 
 has any 
 
never
subject contact and does not collect subject identifiers
  Yes  
  No
3.1d) This is a 
study involving retrospective or prospective medical records.
chart review 
  Yes  
  No
3.1e) This is a 
study occurring in-part or in-full at other locations.
multi-site 
  Yes  
  No
3.1f) There is an 
 component to this research. 
international
International research includes sending or receiving 
human derived data or specimens (identifiable, limited data set, coded, or deidentified) to or from an 
international source.  International research does not include studies in which VA is only one of multiple 
participating sites where the overall study-wide PI is not a VA investigator.
  Yes  
  No
3.1g) This study includes 
 (not including VA-leased space or CBOC clinics) conducted 
off-station activity
under VASDHS IRB approval.  Note: this does not include research conducted by a collaborator at their home 
institution under their institutional approval.
 Yes  
 No
3.1h) VA subjects will 
 in part or in full 
 (not including VA-leased space or 
participate
at other locations
clinics) under VASDHS IRB approval. Note: if this study involves remote participation of subjects, please 


indicate "no" and describe their remote participation in section 9 of the application.  This question is intended 
to understand whether participants must physically go to a non-VA location to participate in this VA research 
study. 
 Yes  
 No
 Section 3.2 Specimen Use and Data Repository
Indicate whether or not each of the following applies to this protocol
3.2a) Involves specimens that are left over from pathological or diagnostic testing (
)
non-research specimens
  Yes  
  No
3.2b) Involves 
 purposes 
specimens collected for research
only
  Yes  
  No
3.2c) This study includes 
 (specimens are retained for use outside of the purposes of this 
specimen banking
protocol)
  Yes  
  No
3.2d) The study involves 
genotyping or other 
DNA 
genetic analysis
  Yes  
  No
3.2e) Biological
will be sent outside of the VA.
 specimens/material 
  Yes  
  No
3.2f) A 
 is maintained (data are retained after completion of the protocol for other uses, 
data repository
 see  before checking "yes")
IMPORTANT:
?
  Yes  
  No
3.2g)  
of the VA (identifiable, coded, limited data set, or deidentified)
Data will be shared outside 
  Yes  
  No
 Section 3.3 Treatment and Clinical Trials
Indicate whether or not each of the following applies to this protocol
3.3a) Includes a 
 component (a research treatment)
treatment
 Yes  
 No
3.3b) Study is a 
  
clinical trial. Note:  A clinical trial is a research study in which one or more human subjects 
are 
 (which may include placebo or other control) to 
prospectively assigned to one or more interventions
evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.
 Yes  
 No
3.3c) Has a data safety monitoring board (
or data safety monitoring committee.
DSMB) 
  Yes  
  No
3.3d) Has a 
 (but not a DSMB) (this is not the data security plan, it is a safety plan).
data safety monitoring plan
 Yes  
 No
 Section 3.4 Drugs and Devices
Indicate whether or not each of the following applies to this protocol


3.4a) 
 that require 
 action such as an Investigational New Drug (IND) approval or exemption or 510
Drugs
FDA
(k) approval.
 Yes  
 No
3.4b) Other drugs, supplement, etc. that
action for inclusion in the study.
 do not require FDA 
  Yes  
  No
3.4c) Medical 
 IDE approval or waiver
devices requiring FDA
  Yes  
  No
3.4d)
 medical 
 Other
devices
  Yes  
  No
 Section 3.5 Risk and Hazards
Indicate whether or not each of the following applies to this protocol
3.5a) Study places subjects at 
(do not include risks that are due to standard care)
greater than minimal risk 
 Yes  
 No
3.5b) Human subjects are exposed to 
 (do not include standard care).
radioisotopes
  Yes  
  No
3.5c) Subjects have other 
 (e.g., x-rays) (do not include standard clinical use).
radiation exposure
  Yes  
  No
3.5d) Target population has psychiatric diagnosis or behavioral complaint.
 Yes  
 No
 Section 3.6 Clinical Facilities and Standard Care
Indicate whether or not each of the following applies to this protocol
3.6a) Study 
 (e.g., adds required tests run in the VA lab for study purposes; research 
uses VA clinical services
procedures concurrent with clinical care)
  Yes  
  No
3.6b) Includes procedures or drugs that will be considered part of standard care.
  Yes  
  No
3.6c) Involves 
purposes.
lab tests done for research 
  Yes  
  No
 Section 3.7 Subject Expenses and Compensation
Indicate whether or not each of the following applies to this protocol
3.7a) There may be expense or added 
or the subject's insurance.
costs to the subject 
  Yes  
  No


3.7b) This is a 
 and subjects may be billed for study drugs or procedures.
qualifying cancer treatment trial
  Yes  
  No
3.7c) This is a cancer treatment trial but 
 for study drugs or procedures.
subjects will not be billed
  Yes  
  No
3.7d) Subjects will be
(either in cash or other means such as a gift certificate).
 compensated 
 Yes  
 No
 Section 3.8 Subject Activities
Indicate whether or not each of the following applies to this protocol
3.8a) Involves 
 completed by subjects
surveys or questionnaires
 Yes  
 No
3.8b) Includes the use of 
 such as flyers, advertisements, or letters
recruitment materials
 Yes  
 No
3.8c) Involves facial 
 or audio or video 
of 
photographs
recordings 
patients
 Yes  
 No
 Section 3.9 Sponsors and Collaboration
Indicate whether or not each of the following applies to this protocol
3.9a) This research is a funded research project (commercial (industry) sponsor, NIH, VA, other).
 Yes  
 No
3.9b) Other 
is provided (e.g., drugs or supplies).
commercial (industry) non-financial support 
  Yes  
  No
3.9d) The protocol has 
 involvement (e.g., subjects or funding).
Department of Defense
  Yes  
  No
3.9c) The PI or other study staff member has a financial interest or other
related to 
 real or potential conflict 
this study.
  Yes  
  No
3.9e) This study involves 
research activities (research conducted at other institutions under the 
c llaborative 
o
authorities or approvals of the other institution/s). Note: this may include other VA and/or non-VA institutions, 
but does not include off-site VA research.
  Yes  
  No
 Section 4 - Estimated Duration
4) What is the estimated duration of the entire study?  (From IRB approval to IRB closure)
12 months
 Section 5 - Lay Language Summary


5) Provide a summary or synopsis of the proposed study using non-technical language (not more than 1 
paragraph)
In 2019 VA mandated that all Veterans seeking mental health care have access to flexible family 
mental health services in VA (VHA directive 1163.04). This study aims to respond to this 
mandate by further improving an evidence-based PTSD treatment designed to decrease PTSD 
symptoms and improve relationship satisfaction for Veterans and their romantic partners. Brief 
Cognitive-Behavioral Conjoint Therapy (B-CBCT), an 8-session dyadic psychotherapy for PTSD, 
has been found to significantly reduce PTSD symptoms, but the effects of B-CBCT on relationship 
satisfaction are less reliable and robust. Pharmacological augmentation of psychotherapy utilizing 
intranasal oxytocin, a neurohormone that influences mechanisms of trauma recovery and social 
behavior, may help improve relationship satisfaction outcomes. If successful, the proposed study 
will advance knowledge of strategies for improving Veterans’ quality of life by improving their 
intimate relationships along with PTSD symptoms.
 Section 6 - Specific Aims
6) Provide a statement of specific aims and 
 that serve as the basis for this protocol.  Emphasize 
hypotheses
those aspects that justify the use of human subjects.
The goal of this proposal is to examine the initial clinical feasibility of B-CBCT augmented with 
intranasal oxytocin (B-CBCT + OT) for improving relationship satisfaction in an open trial among 
twenty dyads composed of Veterans with PTSD and their intimate partners. We also plan to 
explore secondary outcomes such as PTSD symptoms, other aspects of social functioning, and 
quality of life. 
In addition to establishing feasibility of methods (i.e., recruitment and retention of dyads and 
acceptability to participants), specific hypotheses for this project are as follows:
• Primary Hypothesis: There will be improvements in each partner’s self-reported relationship 
satisfaction measured by the Couples Satisfaction Index following completion of B-CBCT + OT.
• Secondary Hypotheses: Following the completion of B-CBCT + OT, Veterans will report 
improvements in PTSD symptoms measured by the PTSD Checklist for DSM-5, psychosocial 
functioning measured with the Brief Inventory of Psychosocial Functioning, and quality of life 
measured with the World Health Organization Quality of Life – BREF. 
 Section 7 - Background and Significance
7) Provide a succinct discussion of relevant background information to justify performing the proposed study.
Interpersonal relationships are critical to Veterans’ recovery from trauma and PTSD.
Military Veterans often experience challenges when reintegrating into their communities after 
their military service, due in part to mental health problems such as posttraumatic stress disorder 
(PTSD). PTSD, a psychiatric disorder that develops in response to exposure to traumatic events, 
such as military combat and sexual assault, disproportionately affects Veterans, leads to poorer 
physical health, and impairs psychosocial functioning and quality of life.
 Mitigating the 
12,28,29
negative effects of PTSD on Veterans’ health, functioning, and well-being is therefore a major 
goal of the Veterans Health Administration (VHA). 
The premise that interpersonal relationships play a key role in resilience, risk, and recovery from 
trauma
 is supported by research showing a robust association between PTSD and social support.
11
 Longitudinal research shows that this association changes over time; during early trauma 
34
recovery, positive social support is associated with reduced likelihood of developing PTSD; at later 
stages of trauma recovery, PTSD symptoms degrade social support.
 The quality of social 
35
environments before trauma exposure are important, too; for example, family problems before or 
after a deployment increase risk of PTSD.
 Treatment approaches that bolster Veterans’ internal 
36
strengths and enhance the capacity of their social environments to provide support are most 
likely to have powerful effects on well-being.
 Post-deployment programs for recently separated 
33
Veterans often emphasize the role of relationships in promoting reintegration.
 Many Veterans in 
37
the VA, however, have chronic PTSD, often accompanied by problems of impairment in social 
functioning and poorer quality of life.  


VA is invested in improving Veterans’ intimate relationships to support their trauma 
recovery. 
Many Servicemembers and Veterans with PTSD experience impairment and distress within 
intimate relationships at greater levels than among civilian couples.
 Consistent with this, 
15
Veterans seeking treatment for PTSD often identify relationships as targets of intervention
 and 
17
express the desire to involve close others in treatment.
 The VA has been responsive to these 
18
needs, as shown by the continuum of services available to Veterans and their families through the 
VA Family Services program. The Veterans’ Mental Health and Other Care Improvements Act of 
2008 (Public Law #110-387, Title III §301 - Assistance for Families of Veterans) stated that 
marriage and family counseling were to be available to Veterans to facilitate their treatment and 
rehabilitation. In 2009 VA began an initiative to select evidence-based family therapies and train 
mental health providers in these treatments. More recently, Directive 1163.04 indicated that 
Veterans with a mental health diagnosis should be asked about their interest in having family 
involved in their care and be offered marital and family counseling. The VA Family Services 
program supports several treatment approaches to meet the diverse mental health needs of 
Veterans and their loved ones. One such option for Veterans who want to simultaneously improve 
their PTSD symptoms and their relationship functioning is Cognitive-Behavioral Conjoint Therapy 
(CBCT) for PTSD.
 The VA has been disseminating CBCT since 2013.
19
Effects of CBCT on Veterans’ relationship satisfaction may be less robust than its effects 
on PTSD. 
CBCT is a PTSD-specific cognitive-behavioral psychotherapy attended by the couple that uses 
close relationships as the vehicle for recovery.
 Across fifteen 1.25-hour sessions, this 
19
manualized therapy addresses the patient’s PTSD, the partner’s well-being, and relationship 
functioning simultaneously via its focus on psychoeducation about PTSD within relationship 
contexts, social skills, behavioral approach exercises, and cognitive interventions. CBCT 
effectively treats PTSD, exhibiting large within-group effect sizes on clinician-rated PTSD 
symptoms.
 
20
Across studies, however, CBCT has had less robust, more variable effects on relationship 
satisfaction than on PTSD. This is likely because the factors governing relationship satisfaction—in 
general and within couples in which a partner has PTSD—are complex and rely on a number of 
independent, interpersonal factors. The largest published study of CBCT (  = 40 dyads), in which 
N
CBCT was compared to a waitlist control group, found a moderate within-group effect (  = 0.64) 
g
and between-group effect (  = 0.47) of CBCT on Veterans’ relationship satisfaction.
 This 
g
20
sample, however, was composed of only about 25% Veterans. Given that Veteran couples are 
known to have lower relationship satisfaction than non-Veteran couples
, it is important to 
15
further examine CBCT among Veteran couples that are more representative of couples seen in 
general VA practice to increase generalizability of findings. However, preliminary data from 
couples treated as part of VA’s dissemination of CBCT suggest that effects on relationship 
satisfaction are noticeably smaller than in previous studies (personal communication, S. Glynn). 
This may be due, in part, to poor engagement in the intervention. Couples experience many 
logistical obstacles to engaging in care (e.g., the need to coordinate schedules, lack of childcare). 
Veterans with PTSD can encounter additional obstacles related to beliefs about mental health and 
mental health treatment. Given these obstacles to treatment engagement, the field must develop 
ways of ensuring that when a couple expresses interest in treatment, so they can have their 
needs met as effectively and efficiently as possible.
To this end, Dr. Leslie Morland (PI) recently completed a study of an 8-session version of CBCT 
(B-CBCT) delivered either in-office or via telehealth to home compared to a family education 
control condition, designed to improve access to and retention in care.  She and her team 
similarly found robust reductions in PTSD symptoms in B-CBCT (B-CBCT within-group 
1.05-
d’s = 
1.12, between-group 
= 0.59-0.76) but only a small effect on both partners’ relationship 
d’s 
satisfaction that was on par with the family education condition (B-CBCT within-group  = 0.38; b
d
 
etween-group 
 = 0.04-0.12).
d’s
Medication augmentation is a promising strategy for enhancing outcomes of behavioral 
interventions.
Medications that potentiate the mechanisms of action in psychotherapy could enhance their 
effects.  The neuropeptide oxytocin in particular appears to be a promising medication because it 
9
mediates processes central to PTSD and relationship functioning. Oxytocin is a 9-amino-acid 
nonapeptide hormone produced by the paraventricular and supraoptic nuclei of the hypothalamus 
that regulates human emotions, social cognition, and social behaviors.
 Endogenous oxytocin 
57
assists in milk production for breastfeeding, induces contractions during childbirth, is released 
during orgasm, may reduce urine volume, and may induce sodium release from the kidneys. 
Intravenous oxytocin is used in medical practice to induce labor in pregnant women and to 


increase muscle tone in the uterus in the case of postpartum bleeding. Oxytocin is released to 
several brain areas, including the amygdala, hypothalamus, hippocampus, insula, and striatum,
 
58
and effects are mediated by oxytocin receptors found in these regions.
  
59
Intranasal administration of oxytocin is an elegant approach for understanding the causal effects 
of oxytocin on human behavior. Intranasal oxytocin is safe and easy to administer,
 with a short 
60
half-life that makes it highly suitable for adding to behavioral interventions. Intranasal oxytocin is 
best known for its widespread effects on affiliative processes and behaviors. For example, 
intranasal oxytocin increases trust
, empathy
, generosity
, positive communication
, and 
22
23
61
24
emotional disclosure.
 Oxytocin also improves social cognition, including emotion recognition
 
62
22
and empathic accuracy.
 The combination of intranasal oxytocin with provision of social support 
63
suppresses cortisol release and subjective responses to social stress.
 
64
Intranasal oxytocin can be conceptualized as a “psychotherapy process catalyst” , in that 
9
oxytocin could enhance patients’ openness to intervention, attention to others’ communication, 
and willingness and ability to develop therapeutic alliance
 A recent systematic review of 14 
.67
studies of the effects of intranasal oxytocin on PTSD symptoms concluded that there is tentative 
evidence for the clinical utility of intranasal oxytocin for PTSD,
 although more studies with 
68
chronic administration are needed.
 To date, only one pilot study has examined the effects of 
69
oxytocin-enhanced psychotherapy for PTSD.
 Findings indicated that 
70
participants randomized to 
Prolonged Exposure (PE) for PTSD augmented with oxytocin demonstrated lower PTSD and 
depression symptoms and had higher working alliance scores compared to participants 
 large, two-site phase II RCT of oxytocin-enhanced PE is 
randomized to PE with placebo. A
currently being conducted in the VA by a Collaborator on this project (PI: Dr. Julianne Flanagan; 
NLM: 
. 
NCT04228289)
Intranasal oxytocin is ideally suited to enhance the effects of CBCT on relationship 
satisfaction.
Administering intranasal oxytocin in a safe, therapeutic context in which interpersonal skill-
building takes place is hypothesized to lead to prosocial effects and facilitated recovery. CBCT is 
therefore the ideal treatment platform for oxytocin augmentation. CBCT and oxytocin are both 
inherently interpersonal and could operate in a coordinated, synergistic manner to improve 
relationship satisfaction. For example, increasing Veterans’ trust in their partners and providers 
may promote emotional engagement in CBCT. Increasing Veterans’ empathy for the partner’s 
experience of how PTSD affects their relationship could elicit motivation to remain engaged in the 
treatment. Facilitating positive communication could enhance all aspects of the therapy, including 
both partners’ sharing of thoughts and feelings and their ability to join together in cognitive 
restructuring of trauma-related beliefs that interfere with recovery. Findings that intranasal 
oxytocin increases neural activation to socially rewarding stimuli
 and facilitates social approach 
73
behavior
 suggest that it could help Veterans and their partners embrace social situations, which 
26
is central to CBCT behavioral interventions. Lastly, generalization of improvements in trust, 
empathy, positive communication, and approach behavior could help Veterans participate more 
fully with their families (e.g., improved parenting skills) and many other domains of society (e.g., 
engagement in education and employment). To date, however, oxytocin has not been tested as 
. 
an adjuvant to CBCT nor any relationship-focused therapy for trauma-exposed Veterans
Intranasal oxytocin pharmacodynamics and dosing considerations. 
Based on compelling pre-clinical data implicating the oxytocin system in affiliative behavior, the 
study of intranasal oxytocin in humans expanded very rapidly. However, these developments 
were followed by calls for caution after acknowledgment of lack of replicability of findings, 
methodological limitations such as low statistical power, and poor understanding of the 
pharmacodynamics of intranasal delivery of synthetic oxytocin.
 Intranasal oxytocin is thought 
6,74
to exert effects by bypassing the blood-brain barrier and reaching the brain directly (i.e., nose-to-
brain transport), but definitive data have been lacking.
 More recently, pre-clinical, primate, and 
75
human research have converged to indicate that intranasal oxytocin does, in fact, reach the brain 
to a degree that leads to clinically relevant changes in behavior, ostensibly through olfactory and 
trigeminal nerve fibers.
 Another issue that has affected the translation of oxytocin 
67,75,76
research to treatment has been the lack of dose-ranging studies in humans. Notably, most 
intranasal oxytocin studies have administered only one dose of intranasal oxytocin, typically 24 or 
40 international units. The pharmacodynamics of repeated oxytocin administration are not well-
established
, but given the short half-life of intranasal oxytocin (i.e., 20 or more minutes in 
69
cerebrospinal fluid
 and 2 minutes in blood
), repeated dosing (e.g., daily, weekly) is not 
77
78
hypothesized to operate differently than single doses. 
Significance and relevance to Veterans and VA patient care mission. 


The proposed study to augment CBCT with intranasal oxytocin and to examine its effects on 
intimate relationship adjustment, social functioning more generally, and quality of life directly 
addresses the mission of the VA, as outlined in the VA FY 2018–2024 Strategic Plan. Specifically, 
the proposed study seeks to advance knowledge of how to help Veterans have good quality of 
life—which the VA identifies as including satisfying relationships—in three ways: First, findings 
from the proposed study will inform whether B-CBCT social functioning outcomes can be 
improved with adjunctive medication. By potentiating the effects of B-CBCT with oxytocin, we 
could increase the clinical response rate of patients and their loved ones receiving B-CBCT. 
Second, if oxytocin enhances the mechanisms described in this proposal as predicted, it could 
further strengthen rationale for providers administering eight-session B-CBCT rather than 15-
session CBCT. Effectively truncating CBCT would mean that more patients could be seen by the 
same number of VA providers, potentially improving Veterans’ access to treatment. Greater 
effectiveness and efficiency of treatment could lead to lower costs to VA. Third, by targeting 
mechanisms that are salient not only to intimate relationships but all interpersonal relationships 
(such as trust) oxytocin could help the effects of CBCT extend to other, non-intimate 
relationships, thereby improving overall quality of life and potentially having downstream effects 
on other issues facing the VA (such as suicide) which is known to be related to interpersonal 
difficulties. Lastly, improving Veterans’ social environments could help them maintain their gains 
and respond effectively to future stressors—potentially lowering the likelihood of future need for 
episodes of care.
 
 Section 9 - Design and Methods
9) Describe the research design and the procedures to be used to accomplish the specific aims of the 
project.  Provide a precise description of the planned data collection (include what systems or databases will 
be used/accessed to gather data), analysis and interpretation.  For chart review studies, include the timeframe 
of collection.  Address sample size, inclusion of women and minorities.  Define in clear terms exactly what will 
 
be done to the human subjects.
STUDY DESIGN OVERVIEW:
This pilot study will enroll up to 20 couples (40 individuals) in B-CBCT + OT over this 12-
month project. Participants will be recruited from the San Diego VA Healthcare System. Couples 
will participate in 8 sessions of B-CBCT augmented with 40 IU of intranasal oxytocin administered 
30 min before each session. At baseline and post-treatment, dyads will be asked to complete 
brief assessments of the outcomes described above. After treatment, they will also provide 
feedback about factors associated with feasibility of methods and treatment engagement. 
Quantitative and qualitative data will be used to assess the feasibility and acceptability of the 
intervention and will be utilized in preparing a proposal for an RCT. We will compare within-group 
effect sizes on PTSD and relationship satisfaction to effects observed within the historical controls 
from Dr. Morland’s RCT of B-CBCT.
 
RESEARCH SITE: 
This pilot study will be conducted at the VA San Diego Healthcare System.
 
PARTICIPANTS:
Participants will be 20 Veteran couples (i.e., 20 Veterans and their 20 partners; 40 
individuals total) who are interested in receiving couples therapy for PTSD and relationship 
problems. Couples of all genders, ages, and ethnicities will be included. Participants must enroll 
and participate together as a couple; if one partner is not interested in participating, the couple 
will not be enrolled, and referrals for alternative individual services will be offered.
Inclusion criteria for the study will require one member of the couple be a Veteran 
enrolled in the San Diego VA Healthcare System with a Posttraumatic Stress Disorder 
Checklist-5 score of > 33, indicating a likely PTSD diagnosis. Veterans must agree not to 
receive other individual or conjoint psychotherapy for PTSD during participation in the 
study. If already on psychoactive medication prior to study referral, Veteran participant 
must remain on a stable psychoactive medication regimen for at least 45 days.


Exclusion criteria will be acute suicidality; psychosis; active substance use disorder; 
severe ongoing medical problems, including heart disease and neuroendocrinological 
disorders (e.g., diabetes); uncontrolled hypotension (systolic blood pressure <100 mm 
Hg) or hypertension (>160/100 mm Hg); pregnancy, delivery in the past 6 months, or 
current breastfeeding; or severe intimate aggression reported by either partner 
(established with validated measures). A list of alternative resources will be provided to 
ineligible participants.
 
DESCRIPTION OF THE BRIEF CBCT INTERVENTION:
CBCT is a manualized couple-based intervention for PTSD designed to simultaneously 
reduce PTSD and enhance relationship functioning. The brief version of the therapy (B-CBCT) 
consists of eight 75-minute sessions organized into two phases that build upon each other and 
includes both in- and out-of-session exercises to increase skill acquisition. Phase 1 (Sessions 1–2) 
focuses on the rationale for the therapy and establishing safety within the relationship (e.g., 
recognizing early warning signs of anger, use of conflict management strategies). Phase 
2 (Sessions 3-7) focuses on increasing relational satisfaction and undermining PTSD-related 
distress. The ways avoidance can generalize beyond specific trauma memories and the role of 
avoidance in maintaining both PTSD and relationship problems are addressed. Couples develop a 
list of people, places, situations, and feelings that they have avoided as a result of PTSD and 
begin in vivo exposure exercises to approach these situations in a graduated manner. Special 
attention is paid to the selection of in vivo approach activities that will address behavioral and 
experiential avoidance, and concurrently double as shared rewarding activities for the couple. 
Enhanced dyadic communication is used as an antidote to PTSD-related emotional numbing and 
avoidance, as well as a means of increasing emotional intimacy. The final session (Session 8) 
culminates with a discussion of the potential for consolidating newly acquired skills and a review 
of gains made and challenges expected in the future. B-CBCT will be delivered via video 
teleconferencing.
 
TREATMENT DELIVERY MODALITY: 
Couples must have access to DSL or cable internet service. B-CBCT will be delivered to 
couples via their personal computer if it is in a private, quiet setting within their home. Project or 
VA IT staff will be available for home-based equipment set-up if necessary. To assure patient 
confidentiality and HIPAA compliance, we will use VA-approved CVT software (AK Summit 
software with FIPS level encryption). The most recent Home-Based Telemental Health Standard 
Operating Procedures Manual will be used to best implement B-CBCT. Please see Humans Subject 
document for further participant safeguards in place.
 
DESCRIPTION OF INTRANASAL OXYTOCIN:
              A 40 IU dose of oxytocin will be self-administered by the Veteran with PTSD only (not 
the partner) intranasally 30 minutes prior to the start of each weekly B-CBCT session. A 40 IU 
dose has demonstrated extensive safety and efficacy, is within the normal dosing range, and is 
one of the most common concentrations utilized in human research
. The medication 
60,73
administration protocol is based on previous research by Dr. Flanagan (Collaborator), a leading 
oxytocin researcher in the area of PTSD, and others.
 While intranasal oxytocin has most 
10,70,94
frequently been used in studies utilizing single doses, several recent published studies of repeated 
dosing have provided evidence of safety in clinical populations
, including a study of once-
64,43,44
weekly dosing for eight weeks among Veterans with PTSD conducted by Drs. Flanagan and Sippel 
(Collaborators).45
           The study prescriber (Dr. Jeanne Maglione) will verify study eligibility and provide 
prescriptions for oxytocin to the VA Research Pharmacy. Oxytocin will be compounded, 
refrigerated, and shipped directly to the participant’s home with administration and refrigerated 
storage instructions by Harbor Compounding Pharmacy in Costa Mesa, CA with operational 
support from the VA Pharmacy, which will be responsible for sending prescriptions and 
documenting the medication in Veterans’ medical charts. Research staff will instruct participants 
on the correct method of administration to achieve the 40 IU dose and will observe participants’ 
self-administration via Veterans Video Connect (VVC). 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. Side effects and adverse events will be evaluated weekly.
 


TREATMENT PROVIDERS:
Treatment will be provided by clinicians (“Intervention Specialist” [IS]) who have a 
Master’s degree or higher and a minimum of 2 years of clinical experience. B-CBCT providers, 
Katelyn Webster, Kayla Knopp, and Chandra Khalifian, are trained on B-CBCT and 
have administered the therapy on a four-year clinical trial to fidelity.
The research pharmacist at VA San Diego (Steven Funk, PharmD) is facilitating the 
procurement of intranasal oxytocin from Harbor Compounding Pharmacy in Costa Mesa, CA. Dr. 
Jeanne Maglione, a VA psychiatrist, will oversee the prescription of oxytocin.
 
ASSESSMENT ADMINISTRATION:
The assessment protocol will include well-validated measurement in the spheres of 
safety, desirability, and symptoms/functioning for each participant (i.e., Veteran and partner) at 
baseline, post-intervention (i.e., after all eight sessions have been completed), and three months 
post-intervention. Depending on participant preference, assessment may be completed over the 
phone or documents can be returned via encrypted email (using VA Azure RMS). Pre-treatment 
and post-treatment assessments will occur approximately 20 to 28 weeks apart. The study will 
also include qualitative interviews with couples to improve study delivery and methods. 
 
DATA COLLECTION:
Responses to measures at all assessment time points are collected with each partner individually 
with the other partner leaving the room to avoid coercion or fear of reprisal if one partner were to 
disclose disqualifying information such as domestic violence. Participants will complete the 
following measures prior to study enrollment to determine if inclusion/exclusion criteria are met:
PTSD Checklist for DSM-5 (PCL-5; Weathers et al., 2013) – 20-item self-report measure 
for the past month that assesses symptoms of PTSD based on the DSM-5; scores at or 
above 33 indicate probable PTSD. Couples will be included if the veteran partner scores at 
or above 33 on this measure.
Columbia-Suicide Severity Rating Scale (C-SSRS; Posner et al., 2011) – 8-item self-report 
measure of suicidal ideation, plan, and intent. Individuals who endorse acute suicidality 
will be excluded from the study.
IPV Assessment-Extended (IPV-5) – assesses behaviors that individuals engage in during 
conflict with their partner as well as past and current fear and intimidation in the 
relationship. Couples with individuals who endorse any severe physical assault behaviors 
in the past year will be excluded from the study.
Alcohol Use Disorders Identification Test (AUDIT; Bohn et al., 1995) – measures 
problematic substance use. Individuals endorsing symptoms of an active substance use 
disorder will be excluded.
 
Additional measures administered at baseline assessment only include:
Traumatic Life Events Checklist (TLEC; Blake et al., 1995) – a 17-item self-report scale 
that assesses for a lifetime history of exposure to traumatic events (veteran only)
Demographic information and 
 (both 
past experiences receiving mental health treatment
partners)
Coronavirus Stressor Survey – assesses stress related to COVID19 (both partners)
 
The primary (relationship satisfaction) and secondary (PTSD symptoms, quality of life) outcomes 
will be assessed with both partners at baseline, post-intervention, and three months post-
intervention using the following quantitative measures:
Couples Satisfaction Inventory-32 (CSI-32; Funk & Rogge, 2007) – a well-validated 
measure of relationship satisfaction 
Changes in Sexual Functioning Questionnaire Male Clinical (CSFQ-M; Keller et al., 2006) – 
the male version of a 14-item measure that provides a brief measure of sexual functioning 
with good construct validity and internal reliability 
Changes in Sexual Functioning Questionnaire Female Clinical (CSFQ-M; Keller et al., 
2006) – the female version of a 14-item measure that provides a brief measure of sexual 
functioning with good construct validity and internal reliability


Intimate Safety Questionnaire (ISQ, Cordova & Blair, 2014) – a 28-item measure of the 
degree to which partners feel safe being vulnerable with each other across several 
different domains of the relationship
PCL-5 – described above for PTSD+ partner. Will also include version for non-PTSD+ 
participants (PCL-C) that asks about the extent to which they perceive their partners have 
experienced PTSD symptoms in the past week
 (B-IPF; Kleiman, Bovin, & Black, 2020) – a 7-
Brief Inventory of Psychosocial Functioning
item self-report measure of past month psychosocial functioning with good psychometric 
properties. The measure will be amended to assess functioning in the past two weeks and 
administered biweekly with the CSI-4 throughout treatment.
World Health Organization Quality of Life – BREF (WHOQOL-BREF; The WHOQOL Group, 
1998) – assess quality of life. It consists of 26 items that measure physical and 
psychological health, social relationships, and environment.
 
Measures for other broader outcomes to be assessed at baseline, post-intervention, and three 
months post-intervention include:
Dyadic Adjustment Scale-7 (DAS-7; Hunsley, Best, Lefebvre, & Vito, 2001
– the self-
)  
report DAS-7 is based on the original 32-item measure. It assesses domains of 
relationship functioning and has demonstrated strong psychometric properties
Patient Health Questionnaire-9 (PHQ-9; Kroenke, Spitzer, & Williams, 2001) – measures 
depressive symptomatology
Brunnsviken Brief Quality of Life Scale (BBQ; Lindner et al., 2016) – measures subjective 
quality of life
Significant Others Responses to Trauma (SORTS) Inventory (Fredman et al., 2014) – 
measures partner responses to PTSD symptoms and will be completed by non-PTSD+ 
partners only
Experiences in Close Relationships-Revised (ECR-R; Franley, Waller, & Brennan, 2000) – 
measures adult attachment style
 
Measures administered at post-assessment only include:
Client Satisfaction Questionnaire (Attkisson, 1982) – measures client satisfaction with the 
intervention they received
Qualitative Feedback Questionnaire – captures verbal feedback from participants regarding 
their experience of the study
 
Prior to each B-CBCT session, each participant will complete brief self-report assessment 
measures for the primary and secondary outcomes. The outcomes measures are listed below. The 
Veteran participant will complete a questionnaire assessing any side effects of the intranasal 
Oxytocin. If the Veteran participant is able to become pregnant, she will also take a pregnancy 
test.  
PCL-5 and PCL-C (Weathers et al., 2013) – past-week version for PTSD+ participant and 
partner respectively
Couples Satisfaction Inventory-4 (CSI-4; Funk & Rogge, 2007) – a well-validated and brief 
(i.e., 4 items) measure of relationship satisfaction completed by both partners
 
No PII will be stored with participants' data; data will be identified by coded study 
identifier only. Electronic deidentified data will be stored on restricted VA research servers 
accessible only on VA-networked, password protected computers. Records linking coded study 
identifiers to participants' identifiable information will be kept separately from any data, and 
electronic records will be password-protected. Any hard-copy data (e.g., transcribed 
questionnaires) will be stored in locked file cabinets in locked offices in Dr. Morland's office space 
in the San Diego VMRF/HSR&D Building (Building 13), with any identifiable hard-copy data being 
stored separately from coded research data.
If able to become pregnant (i.e., assigned female at birth, fertile, following menarche 
and until becoming post-menopausal unless permanently sterile), the Veteran participant will be 
required to take a pregnancy test (provided by study staff) at baseline assessment and weekly 
during treatment before self-administration of oxytocin. A participant is considered not able to 
become pregnant if they are premenarchal, surgically sterile (documented hysterectomy, bilateral 
salpingectomy, bilateral oophorectomy, and/or tubal ligation), postmenopausal, or assigned male 


at birth. These pregnancy tests will be purchased by the study and mailed to Veteran participants 
who are able to become pregnant only. Veteran participants who are able to become pregnant 
will be required to verbally confirm a negative result prior to continuing with each oxytocin 
administration.
 Section 9.2 IND Drugs
9.2) For each drug requiring an IND, provide the drug name, dose, and route of administration
Name: Oxytocin 
Trade Name: Pitocin 
Description: Peripherally, oxytocin causes the contraction of uterine smooth muscle and of the 
myoepithelial cells within the mammary gland. In the central nervous system, oxytocin is a 
modulator of social behaviors, facial recognition, fear, anxiety, and trust. Oxytocin is metabolized 
by hepatic oxytocinases and disposed by biliary and renal excretions. 
Molecular Formula: C43H66N12O12S2 
Chemical Structure: Cysteine - tyrosine - isoleucine - glutamine - asparagine - cysteine - proline 
- leucine - glycine (CYIQNCPLG)
Pharmacologic Class: Neuropeptide 
Formulation: Each 1.5 mL vial contains 60 units/mL (.1056 mg/mL). 
Route of Administration: Intranasal 
Storage and Stability: Refrigerator (2°-8°C)
Clinical studies of the effects of intranasal oxytocin administration have been conducted 
successfully worldwide for more than 10 years. In the US, intranasal administration of oxytocin is 
used in clinical studies, similar to the proposed one, in two possible routes: 1. Under an IND 
from the FDA. 2. Under an IND exemption (described here; Kubzansky et al 2009). 
We are seeking an exemption from IND filing requirements for a clinical investigation of a drug 
product that is lawfully marketed in the United States under exemption category 1. The intention 
of the investigation is NOT to report to the FDA as a well-controlled study in support of a new 
indication for use or to be used to support any other significant change in the labeling for the 
drug. The drug that is undergoing investigation is lawfully marketed as a prescription drug 
product, and the intention of the investigation is NOT to support a significant change in the 
advertising for the product. Lastly, the investigation does NOT involve a route of administration 
or dosage level or use in populations or other factor that significantly increases the risks (or 
decreases the acceptability of the risks) associated with the use of the drug product.
To our knowledge, oxytocin was never found to have been withdrawn from investigation or 
marketing in any country due to any safety or efficacy related reasons. The application of the 
substance is considered safe for administration to human subjects under the conditions of the 
study since intranasal oxytocin at this dosage is known from decades of use to be safe and well 
tolerated, as evidenced by their routine usage in protected patient populations, such as nursing 
mothers (The nasal form of Oxytocin – Syntocinon, manufactured by Novartis Pharma – is listed 
in the FDA website as being used routinely from the 1962 until 1995). The only contraindications 
are known hypersensitivity reactions to oxytocin. The dosage proposed in this study conforms to 
clinical doses and have been used previously in normal and clinical volunteers for research 
studies by others and ourselves, including Collaborator Dr. Julianne Flanagan in a VA-funded 
study. Any side effects for this application form are rare, and no serious side effects have been 
recorded for intranasal application of up to 60 IU OT (Epperson et al. 1996). Nausea and 
vomiting, and transient cardiac arrhythmias have been described rarely. In addition, anaphylactic 
reactions are described in the data sheet, although the medical literature only contains case 
reports related to intravenous application of OT.
Furthermore, a previous IND exemption (#75429) states, “Intranasal oxytocin has previously 
been approved for marketing in the United States from March 20, 1962 until its withdrawal from 
the market on August 7, 1997.” The Federal Register notice issued on that date [Federal 
Register, Vol. 62, No. 152, Docket No. 97N-0326, pp. 42575 – 42577] clearly states that this 
withdrawal was at the request of the manufacturer, because the drug was no longer being 
marketed. No safety reasons were cited in connection with the withdrawal. The intranasal form of 
oxytocin remains on the market outside of the United States.
Finally, this investigation is conducted in compliance with the requirements for review by an IRB 
and with the requirements for informed consent. This investigation is also conducted in 
compliance with the requirement that the investigation is not intended to promote or commercial 
the drug product.


Since this protocol involves weekly doses of a hormone that has been shown to have minimal 
side effects, a short half-life in adults, and a good safety profile in adults even with chronic 
administration (Horta et al., 2020), an IND exemption appears to be justified. 
9.2b) Enter the IND Number:
9.2c)  Identify who/what entity holds the IND and the status of the IND
9.2d)  Identify the storage and security of the drug.  For example, at the VASDHS, state "The investigational 
drug will be stored in the Research Pharmacy in accordance with 119-SOPP-10/151-SOPP-38."  Also, identify 
whether the drug is a controlled substance.
Oxytocin will be compounded, refrigerated and shipped directly to the participant’s home with 
administration and refrigerated storage instructions by Harbor Compounding Pharmacy in Costa 
Mesa, CA with operational support from the to the VA Pharmacy, which will be responsible for 
sending prescriptions and documenting the medication in Veterans’ medical charts.
 Section 9.8 Questionnaires & Surveys
9.8) Provide the name and a reference for questionnaires/surveys that are standard or identify them here and 
attach a copy of the questionnaire/survey.  Questionnaires or surveys that are not clinical standard references 
must be uploaded.  Reference the help link for additional information related to surveys administered to VA 
 
personnel and approved platforms for web-based surveys.
•Traumatic events at baseline: Traumatic Life Events Checklist 
•PTSD: Posttraumatic Stress Disorder Check List-5 (weekly and monthly versions as well as a 
collateral version for non-PTSD partners)
•Partner’s response to PTSD: Significant Others Responses to Trauma (SORTS) Inventory 
•Couples’ satisfaction: Couples Satisfaction Inventory-32 and -4 item
•Sexual functioning for male partners: Changes in Sexual Functioning Questionnaire Male Clinical
•Sexual functioning for female partners: Changes in Sexual Functioning Questionnaire Female 
Clinical
•Safety and vulnerability in relationship: Intimate Safety Questionnaire 
•Relationship functioning: Dyadic Adjustment Scale-7
•Relationship Conflict at baseline: IPV 5-item screen
•Attachment: Experiences in Close Relationships 
•Functioning: Brief Inventory of Psychosocial Functioning 
•Quality of life: World Health Organization Quality of Life – BREF 
•Depression: Patient Health Questionnaire-9
•Suicidal ideation, plan, intent: Columbia-Suicide Severity Rating Scale 
•Pregnancy test
•Substance abuse at baseline: Alcohol Use Disorders Identification Test 
•Life satisfaction: Brunnsviken Brief Quality of Life Scale 
•Participants’ satisfaction with treatment at post-treatment: Client Satisfaction Questionnaire
•Demographic information and past experiences receiving mental health treatment at baseline
•Questionnaire assessing side effect of intranasal Oxytocin
•Qualitative Feedback Questionnaire
•COVID impact at baseline: Coronavirus Stressor Survey
 Section 9.9 Data Safety Monitoring Board or Plan
9.9) Provide a Data Safety Monitoring Plan (DSMP) or the details of a Data Safety Monitoring Board; if a 
written plan is available, attach a copy of the plan to the submission form.
Consistent with current the CBCT RTC IRB protocol (# H150181), no data safety monitoring 
board (DSMB) is in place; however we will collect data on all adverse events including all 
unscheduled office visits, urgent care visits, emergency room visits, hospitalizations, and deaths. 
All adverse event data will be reported to the Human Subject Sub-committee on an ongoing 
basis. In addition, we will provide interim analyses data on adverse events as part of yearly 
project reports to the IRB and Human Subject Subcommittee.
 Section 9.11 Pictures and Audio/Video Recordings of Patients


9.11) Describe the purpose of photographs (facial), or audio, or video recordings of patients.  Describe 
whether the recordings will contain, or potentially contain, identifiers.  Note: use of photographs or recordings 
must be covered in the informed consent process and documented consent documents (e.g., consent form, 
information sheets, telephone screen scripts).
Consistent with the current CBCT RTC and Connecting Women to Care (CWC) RTC IRB protocols 
(# H150181 and # H170109), the study will collect audio recordings of patient therapist 
meetings and assessments. This study will not collect photographs or video recordings. The audio 
recordings will be used to ensure treatment fidelity and make modifications to the protocol based 
on patient feedback. The recordings will not be used in presentations or for other purposes. 
These recordings are considered PHI under HIPAA and VA definition of PHI. All audio recordings 
will be maintained and stored in accordance with VA guidelines. Only study personnel will have 
access to the audio recordings. Audio-recordings will be deleted when permitted pursuant to the 
VA Record Retention Schedule. Though uncommon, should a participant not agree to be audio 
recorded, this is not exclusion from participation. Appointments with this participant would not 
be audio recorded, however, all other study protocol steps will be completed as usual.
Specifically, these audio recordings will be recorded via USB microphones; these audio files will 
be stored on the study folder on the VA server. The microphones do not store or retain any part 
of the recordings, rather they are directly uploaded. These devices were reviewed by Carol 
Johnson, ISSO, for the CWC Study (protocol # H170109) who concurred that these devices do 
not need IT security approval at that time. The procedures for this study will match those of the 
CWC study.
 Section 9.12 Off Station Activities
9.12) Describe each off-station activity including where it occurs, subject involvement, and any additional 
required protections.  Note:  if the off-station activity is being conducted under the approval authority of another 
institution, this is not VA offsite research and should be described as collaborative research effort.  Please contact 
the HRPP office if you have any questions
Study staff will work with the participants remotely via VA Video Connect, Webex, or the phone 
while the participants are in their homes for the informed consent visit, assessments, and 
therapy appointments. Therapists will work with participants to identify appropriate spaces within 
each participant’s home that is conducive to completing study appointments (e.g., private and 
quiet spaces with appropriate seating). Each session conducted in the home over a video 
teleconferencing modality will be audiotaped using a digital recorder set up by the study 
therapist. Electronic medical records of each Veteran participant will be available to the 
therapists by accessing the VA’s computer network before and after sessions. A progress note for 
each visit will be entered into the Veteran patient’s electronic medical record.
 Section 10 - Human Subjects
10) Describe the characteristics of the proposed subject population. Include age, gender, ethnicity, and health 
status as appropriate.  Note: Data about people are still considered “human subjects” by the IRB, so even if you 
do not intend to contact the patients whose charts you will review, you still describe the characteristics related to 
   
the subjects whose charts you will review.
Provide inclusion and exclusion criteria as appropriate.  Provide a statement how non pregnancy is 
confirmed if pregnancy is an exclusion criteria.
For multisite studies, provide the total number of subjects from all sites and include description of the 
local site's role as a coordinating center if applicable.
Indicate the number of VA participants to be studied.
Indicate the estimated number of 
 subjects that will fail the screening process, if any.
consented
A total of 40 participants will be enrolled: 20 Veterans plus their partners (who may or may not 
also be Veterans). Therefore, between 20 and 40 VA participants will be studied.
Inclusion criteria for the study will be a veteran enrolled in the San Diego VA Healthcare System 
with a Posttraumatic Stress Disorder Checklist-5 score of > 33, indicating a likely PTSD 
diagnosis. Veterans must agree not to receive other individual or conjoint psychotherapy for 


PTSD during participation in the study. If already on psychoactive medication prior to study 
referral, Veteran participant must also be on a stable psychoactive medication regimen for at 
least 45 days. 
Exclusion criteria will be acute suicidality; psychosis; active substance use disorder; severe 
ongoing medical problems, including heart disease and neuroendocrinological disorders (e.g., 
diabetes); uncontrolled hypotension (systolic blood pressure <100 mm Hg) or hypertension 
(>160/100 mm Hg); pregnancy, delivery in the past 6 months, or current breastfeeding; or 
severe intimate aggression reported by either partner (established with validated measures). 
Because the effects of oxytocin on pregnancy outcome are well known, pregnant and lactating 
females will be excluded from the trial. We will instruct participants who are able to become 
pregnant to use appropriate forms of contraception, and we will instruct them to perform urine 
pregnancy tests at baseline and weekly during treatment before self-administration of oxytocin if 
a Veteran participant is considered able to become pregnant.
Consistent with our CBCT trial (IRB protocol # H150181), participants who are not eligible for 
this pilot study will be given information about and, if desired, referrals to appropriate other 
services. Specifically, individuals whose partners are not interested in participating will be 
informed about options for individual therapy in the VA (for Veterans) or community (for 
partners). Couples who report experiencing or perpetrating severe physical or sexual relationship 
aggression will be excluded from the study and referred for individual treatment; the partner 
reporting experiencing interpersonal violence will be referred to local resources for victims of 
domestic violence and given a brochure containing information regarding these resources (see 
Domestic Violence Resources Brochure).
 Section 10.1 Non-Veteran Subjects
10.1a)  Recruitment of non-Veterans cannot be for the sake of convenience for this study.  Provide the 
objective and justification for the inclusion of non-Veteran subjects.  Identify how the research results will be 
generalizable to the Veteran population.  NEW:  ORD now requires completion of a Request to Enroll Non-
Veterans form (available in the help section of OnRAMP) for any VA studies requesting to enroll non-
Veterans.  This form will be reviewed by the local RDC before the application may be considered by the 
 
IRB.  Complete the form and upload with this submission.  
This is a study on adult Veterans and their partners. Therefore, approximately 50% of the 
participants may or may not be a Veteran themselves.
10.1b) Non-Veterans must be given a copy of the VA Notice of Privacy Practices (NOPP) and sign the 
acknowledgement form when their health information is used/collected for research purposes.  In addition, 
the Privacy Officer must be notified of the non-Veteran enrollment and be provided with a copy of the signed 
NOPP, when applicable.  If CPRS notes are entered, and the acknowledgement must also be scanned into 
CPRS.  The NOPP, Acknowledgement form, and instructions to provide the completed form to the PO are 
available under the ? at the top right corner of this page.
 Agree
 Disagree
 Section 11 - Recruitment
11) Describe, step-by-step, the plans for recruitment of subjects (or selection of subjects as in record review). 
This description must include how, when, and where potential subjects are approached as well as procedures 
for identifying potential participants (through medical records, physician referral, third-party 
sources, etc.).  Include how selection is equitable.  Indicate if vulnerability to coercion may be present and if so 
plans to ensure voluntary participation.
Recruitment will primarily occur using existing procedures already in place from the ongoing 
CBCT trial (IRB protocol H150181).
First, we will recruit participants who have (1) agree to be contacted for other research 
opportunities and (2) meet eligibility requirements for this pilot study. We will contact those 
participants via approved means to offer them an opportunity to participate in this pilot study.


Second, we will recruit directly through referrals from the San Diego VA Family Mental Health 
Program (FMHP). FMHP clinical providers will discuss the study with eligible Veterans who are 
waiting for couples services. If the Veteran indicates interest in learning more about the study, 
clinical providers will obtain verbal permission from the Veteran to alert Katelyn Webster (study 
coordinator) and/or Dr. Morland via a CPRS note. Clinical providers will document that that 
Veteran indicated interest in the study and agreed to be contacted by phone in a CPRS note.
Finally, we will recruit participants via referrals from VA providers in other clinics and services, 
including general (e.g., BHIP) or specialty mental health (e.g., PCT) and Primary Care / PCMHI. 
We will work with providers to facilitate direct referrals via the methods described above. 
We will provide a brief informational sheet for providers (not to be shared with participants) 
which will list study facts and inclusion/exclusion criteria. We will also send providers a basic 
study flyer to give to their patients who may be interested in participating.
 Section 11.1 Recruitment Materials
11.1) Identify all recruitment materials (flyers, advertisements, letters, etc.) that will be used; include the web 
address for any web-based advertisements. The text of all communications with prospective participants must 
be reviewed and approved by the IRB before it can be used.  You will be reminded to attach copies of 
recruitment materials to the initial submission packet.  Note:  Posting of flyers with pull tabs is not permitted 
within VASDHS (including the VMRF building).  However, you may request to advertise on the e-boards (located 
 
at the elevators and throughout the facility) or on the VASDHS Research Opportunities web-page.
Recruitment materials (a provider information sheet and participant flyer with basic study facts) 
will be used for the study. A phone screen will be used to screen participants referred to the 
study through the VA Family Mental Health Program, other VA clinics (e.g., PTSD clinic), or self-
referral. 
We will provide a brief information sheet to VA providers (not to be shared with participants) 
which will list study facts and inclusion/exclusion criteria. We will also send providers a basic 
study flyer that they can give to interested patients who want more study information. This flyer 
will include an overview of the research study purpose, details, procedures, and compensation, 
as well as contact information for study staff. The provider information sheet and study flyer are 
attached to this application.
 Section 12 - Informed Consent
12) Indicate whether or not each category of consent is involved in this study:
12a) Will the study team obtain information or biospecimens for the purpose of screening, recruiting, or 
determining the eligibility of prospective subjects without (or prior to) obtaining informed consent of the 
prospective subject or the prospective subject’s LAR?
 Yes  
 No
Check one or both of the below boxes if they apply to this study:
Information will be obtained through oral or written communication with the prospective subject or the subject’s 
Legally Authorized Representative (LAR) and this is not a FDA regulated study.
  Yes  
  No
Identifiable information or biospecimens will be obtained by accessing records or stored identifiable 
biospecimens and this is not an FDA regulated study.
  Yes  
  No
Since both boxes were checked "no", a request for an informed consent waiver is needed.
12b) 
 informed consent
Signed
 Yes  
 No


12c) Waiver of documented consent (e.g., 
consent) for all or part of the study.
oral 
  Yes  
  No
12d) Request for a 
 of consent for all or some study activities.
waiver
 Yes  
 No
12e) Alteration of 
 of consent.
other required elements
  Yes  
  No
12f) 
assent to participate (Director approval will be required)
Child 
  Yes  
  No
12g) Will any language 
 be used by those obtaining consent and understood by the 
other than English
prospective participant or the legally authorized representative?
  Yes  
  No
12h) 
 to determine if participants have the capacity to consent for themselves.
Decisional Capacity Assessment
  Yes  
  No
12i) 
 consent (legally authorized representative)
Surrogate
  Yes  
  No
 Section 12.1 Informed Consent Process
12.1a) Will consent be obtained before any study procedures are performed (including screening procedures 
 
except screening procedures with Consent and/or HIPAA waiver when required)?
 Yes  
 No
12.1b) Will the information being communicated to the participant or legally authorized representative 
during the consent process include exculpatory language through which the participant or legally authorized 
representative is made to waive or appear to waive any of the participant’s legal rights or release or appear to 
release the Researcher, Sponsor, the VA or its agents from liability for negligence.
  Yes  
  No
12.1c) A master list of all VA subjects consented (written or not) under this protocol will be maintained.
 Agree
 Disagree
12.1d) Identify the circumstances under which consent will be obtained including where the process will take 
place; any waiting period between describing the research and obtaining consent including sufficient time for 
the prospective participant to consider participation, and any steps taken to minimize the possibility of 
coercion or undue influence.
Consent will be obtained from both partners during a Webex or VVC telehealth appointment. 
Prior to the appointment, the DocuSign document including approved informed consent, HIPAA 
document, and CA Experimental Subjects Bill of Rights will be sent to the couple. The information 
in the informed consent document will be discussed with the couple during the telehealth visit. 
Specifically, both members of the couple will be informed that their participation is voluntary, 
that all information will be kept confidential [except when information pertaining to threat of 
harm to self (i.e., suicidal intent) or others (i.e., homicidal intent, child abuse, elder abuse) is 
disclosed by one or both members of the couple], and that they can terminate participation at 
any time without negative consequences. They will also be informed that they will complete eight 
75-minute therapy appointments and assessment measures three times (baseline, post-


program, and three months post-program). It will be explained that the purpose of this study is 
to find out whether Brief Cognitive Behavioral Conjoint Therapy augmented with intranasal 
oxytocin results in improvements in PTSD symptoms and relationship satisfaction. It will also be 
explained that both members of the couple must participate to be eligible for the study. 
If either member of the couple cannot demonstrate sufficient comprehension of the consent 
information by briefly explaining the purpose and risks and benefits of the study, the couple will 
not be included in the study and the assessment clinician will refer them for alternative 
treatment.
If interested in participating, couples will sign the DocuSign consent which will be stored in a 
secure electronic research folder (i.e., PI folder on the R drive). During the consent process, we 
will also verbally obtain and transcribe all the information necessary in the event that we need to 
create a collateral medical record for the non-veteran partner. However, we will only open a 
chart if it is needed in order to avoid risk to the partner's confidentiality. We do not typically see 
the partner alone, except as part of the initial consent and assessment. If the partner were being 
seen for something that required documentation (domestic violence, SI, or other safety 
concern), then we would create a collateral chart using the information provided to us during the 
assessment. This procedure matches that of the Family Mental Health Program.
 Section 12.4 Waiver of Informed Consent
12.4a) Is it practicable to conduct the research without the waiver or alteration of consent?
  Yes  
  No
12.4b) Does the research examine public benefit or service programs and is subject to state or local 
government approval?
  Yes  
  No
12.4c) Will the research involve greater than minimal risk?
  Yes  
  No
12.4d) Will waiving or altering informed consent adversely affect the subjects’ rights and welfare?
  Yes  
  No
12.4e) Is it appropriate to provide pertinent information to subjects later BUT this information will NOT be 
provided?
  Yes  
  No
12.4f) Identify to what aspects of the study you are requesting a waiver of consent (i.e., full study or specific 
aspects). Describe the waiver or alteration needed and why it can be granted (include why the research is not 
practical without the waiver or alteration and how the waiver enables conducting the study).
Waiver of informed consent or alteration of consent elements may be allowed if the IRB documents these 
findings and approves waiver or alteration.
The study is not able to be conducted without the waiver since it is necessary that all veteran 
patients be screened over the phone to determine the couple's initial eligibility for the study. It is 
important that we schedule assessment appointments for only those couples that are deemed 
initially eligible at the phone screen, as it would add unnecessary burden to couples for whom 
ineligibility could easily be determined by veteran phone screen if they were required to attend a 
full baseline assessment screening.


12.4g) Explain why the research could not practicably conducted without using identifiable information.
The use of PHI access and use enables us to conduct research as it allows us to communicate 
with participants (both veterans and veterans’ partners). Also, it is required that we document all 
veteran contact and appointments. In rare instances, we may also need to document contact
/appointments with veteran’s partners (e.g., partner discloses SI or IPV concerns). We must 
collect PHI in order to properly document study progress and appointments.
 Section 12.9 HIPAA Authorization
For each category below, indicate whether or not this study involves the indicated process:
12.9a) 
 HIPAA Authorization.  
Signed
**New Template is available in the ?  Help section**
 Yes  
 No
12.9b) HIPAA waiver to cover the entire study
  Yes  
  No
12.9c) HIPAA waiver for recruitment, screening, and/or for a portion of the study.
 Yes  
 No
12.9d) HIPAA Authorization or waiver is 
 for some or all of the study subjects (e.g. no health data).
not required
  Yes  
  No
 Section 12.10 HIPAA Waivers and Alterations
12.10a) Describe the purpose/nature of the HIPAA waiver or alteration and list specifically, what identifiers 
and health information are being requested under the waiver/alteration and identify whether the waiver is 
for access, use, and/or collection of this information.
All referrals for potential participants will come directly from clinical providers after Veterans 
have indicated interest in the study. For Veterans who indicate interest, Ms. Webster will be 
tagged on the CPRS note. Ms. Webster will contact the couple only after they indicate to their 
clinical provider a desire to be contacted (which will be documented on the Veteran’s CPRS note), 
to further describe the study, screen for eligibility, and schedule the couple for a pre-treatment 
assessment session.
Because we will screen Veteran patients for eligibility over the phone, we are requesting a partial 
HIPAA/consent waiver for screening. This will help us eliminate unnecessary burden for those 
couples who may not qualify for the study by not scheduling a full assessment visit, and instead 
facilitating efficient referrals to other appropriate care. At this screen, we will collect the following 
data for the veteran partner: gender, name (first and last), address, phone contact numbers, 
and social security numbers. With the waiver we will utilize the following for looking at 
prospective participants when added as signers to patient CPRS notes: First and Last name, last 
four of the social security number, address, and phone number.
Pre-eligibility screening questions will include: age; Veteran status; scheduling conflicts and 
technology availability; whether or not the individual has been told by a medical provider that he 
or she has a psychotic disorder or a neurocognitive disorder; suicide attempts in the past year; 
pregnancy or recent birth; exclusionary medical condition; and intimate partner violence in the 
relationship. See Phone Screen attachment. These screening procedures match currently 
approved CBCT trial (protocol # H150181) as well as OurRelationship.com Pilot (protocol # 
H190163).
A HIPPA waiver is also necessary to allow for the disclosure of prospective subjects' names and 
email addresses to DocuSign for the purposes of emailing them the consent and HIPPA forms 


prior to the informed consent appointment. HIPAA authorization will be documented using 
Docusign which will be stored in a secure electronic research folder (i.e., PI folder on the R 
drive).
12.10b) The proposed access, use, and/or disclosure of PHI involves no more than a minimal risk to the 
privacy of individuals.
 Agree
 Disagree
12.10c) The plan to protect the identifiers from improper use and disclosure is adequate.
 Agree
 Disagree
Describe the plan
We will never use patient names to identify patients. Instead, we plan to identify all patients 
(veterans and partners) with subject identification numbers. This data will be stored in an 
encrypted Access Database. Only approved study staff will have access to this database.
12.10d) An adequate plan to destroy the identifiers at the earliest opportunity consistent with conduct of the 
research, unless there is a health or research justification for retaining the identifiers or such retention is 
otherwise required by law.
 Agree
 Disagree
12.10d2) Describe the plan:
Data will only be destroyed according to RCS-10 under Records Control Manager guidance.
12.10e) By signing this protocol for submission, the PI is providing written assurance that the PHI will not be 
reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the 
research project, or for other research for which the use or disclosure of protected health information would 
 
be permitted by the Privacy Rule.
:  If the waiver of HIPAA authorization is for 
38 U.S.C. 7332 Information
the use of 38 USC 7332 information (applicable to drug abuse, alcohol abuse, HIV infection, and sickle cell 
anemia records), by signing this protocol for submission the PI is providing written assurance that the 
purpose of the data is to conduct scientific research and that no personnel involved may identify, directly or 
indirectly, any individual patient or subject in any report of such research or otherwise disclose patient or 
subject identities in any manner. (Ref:  38 U.S.C. 7332(b)(2)(B))
 Agree
 Disagree
12.10f) The research could not practicably be conducted without the waiver or alteration.
 Agree
 Disagree
12.10f2) Describe how the waiver/alteration enables the research to be conducted
The study is not able to be conducted without the waiver since it is necessary that all veteran 
patients be screened over the phone. It is important that we schedule assessment appointments 
for only those couples that are deemed eligible at the phone screen, as it would add unnecessary 
burden to couples for whom ineligibility could easily be determined by veteran phone screen if 
they were required to attend a full baseline assessment screening.
12.10g) The research could not practicably be conducted without access to and use of the PHI.
 Agree
 Disagree
12.10g2) Describe why it would be impracticable to conduct this research without the PHI described 12.10a. (v3
/8/18)
The use of PHI access and use enables us to conduct research as it allows us to communicate 


with participants (both veterans and veterans’ partners). Also, it is required that we document all 
veteran contact and appointments. In rare instances, we may also need to document contact
/appointments with veteran’s partners (e.g., partner discloses SI or IPV concerns). We must 
collect PHI in order to properly document study progress and appointments.
 Section 13 - Alternatives to Participation
13) Describe the alternatives to participation in this research study (see  for guidance)
?
The alternative to participation is to not participate or to access standard care via the VA Family 
Mental Health Program or other individual outpatient clinics (BHIP, PTSD clinic, Mood Clinic). 
Alternative psychosocial treatments may include treatment for PTSD or non-trauma-focused 
counseling provided in either an office-based setting or virtually via the VA’s Telemental Health 
program. Pharmacological treatments for disturbances in mood, arousal, and sleep often 
associated with PTSD symptomatology may also be available through the VA. Additionally, 
participants can access a number of other free VA-supported mobile apps and web programs for 
various mental health concerns, as well as non-VA self-help programs and books. The risks of 
these alternate treatments are similar to that of B-CBCT with adjunctive intranasal oxytocin, but 
participants may prefer individual over couple-based treatment, not to take intranasal oxytocin, 
and/or in-person over web-based treatment.
 Section 14 - Potential Risks
14) Describe any potential or known risks or discomforts and assess their likelihood and seriousness (see  for 
?
guidance)
Potential psychological risks of the treatment include exacerbation of PTSD-related anxiety 
during the approach assignments, relationship distress during the couple intervention, and/or 
sadness, tension, or other negative emotions when talking about relationship problems. It is 
possible that, if experienced, some participants will withdraw from the project in response to 
such discomfort. Risks associated with study assessments include the possibility that participants 
may become distressed while answering questions pertaining to their emotional functioning and
/or their relationship, or they may find some detailed questions intrusive. However, our prior 
research experience, including substantial research with distressed couples, suggests that data 
collection using the aforementioned measures can be conducted without undue psychological 
distress or exacerbation of symptoms among participants. This experience includes substantial 
research with distressed couples and those with combat-related or victimization-related PTSD.
Potential physical risks are related to participant use of Oxytocin. Oxytocin is a neuropeptide 
hormone commonly administered intravenously to women during labor and delivery. Risks 
associated with oxytocin administration have been observed with intravenous, but not intranasal 
administration, related to its Food and Drug Administration (FDA)-approved purpose to induce 
labor and facilitate lactation. 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 women. Previous studies show that risks of 
intranasal oxytocin administration are minimal and manageable through the proposed human 
participants protection methods described below (see 4B. Adequacy of Protection from Risk). 
Collaborator Dr. Flanagan has administered intranasal oxytocin at the planned dose of 40 
international units (IU) to over 900 research participants to date, including Veterans with PTSD 
and distressed couples with alcohol use disorder and intimate partner violence, without a single 
severe adverse event reported. Oxytocin is contraindicated for pregnant and lactating women, 
who will be excluded from the trial. Participants may also experience physical or psychological 
discomfort during the medication self-administration.
Social risks of this study center around potential threats to confidentiality. We do not anticipate 
risk of physical, legal, or financial harm as a result of participating in the study. Measures to 
minimize the identified psychological and social risks are described in Protections Against Risks. 
Overall, we feel that we have stringently addressed potential risks to participants and that the 
benefits of the treatment outweigh the risks. Rare but serious risks are with the handling of 
medical and research records, as there is always the possibility of a breach of confidentiality.
Alternative psychosocial treatments generally include individual treatment for PTSD as well as 
non-trauma-focused couples counseling provided in an office-based setting similar to the 
standard services condition offered in our study as well as pharmacological treatments for 
disturbances in mood, arousal, and sleep often associated with PTSD symptomatology. The risks 


of these alternate treatments are similar to that of B-CBCT with adjunctive intranasal oxytocin, 
but participants may prefer individual over couple-based treatment, not to take intranasal 
oxytocin, and/or in-person over web-based treatment. Participants will be informed of these 
alternative treatment options and provided with information on how they may be obtained.
 Section 15 - Risk Management
15) Describe the procedures for protecting against or minimizing any potential risks/discomforts, and the 
adequacy of resources for conducting the study and resources participants may need as a consequence of the 
research.  When applicable, include detail of the following safety measures:   
(a) The type of safety 
information to be collected, including AEs; 
(b) Frequency of safety data collection; 
(c) 
Frequency or periodicity of review of cumulative safety data; 
(d) Statistical tests for analyzing the 
safety data to determine if harm is occurring; and 
(e) Conditions that trigger an immediate suspension 
of the research.  See  for further requirements.
?
As described above, anticipated risks to this study include an increase in negative emotions, such 
as sadness, distress, or anxiety, in response to discussing relationship problems and/or engaging 
approach exercises. Measures to address psychological risks include psychoeducation about PTSD 
symptoms as well as frequency and form of relationship distress. Risk will also be addressed 
through the provision of information concerning the rationale behind the intervention strategies 
used and their potential benefits and side effects (such as an increase in negative emotions), 
instruction in appropriate couple and individual coping and problem-solving skills, and additional 
direct therapeutic interventions, as needed, by an experienced couple therapist. To minimize the 
risk of upset during assessments, participants will complete assessments in private, and all 
participants will be informed at the outset that they may talk to the PI if they have questions or 
concerns about assessment items, as well as decline to answer any questions or terminate their 
participation at any point.
If participants do experience notable distress, they will be provided with contact information for 
licensed psychologists on study staff, including the PI, and follow-up referrals as appropriate. In 
addition, they will be given access to a 24-hour crisis psychiatry telephone service. However, our 
prior research suggests that data collection using the aforementioned procedures can be 
conducted without undue psychological distress or exacerbation of symptoms among 
participants. This experience includes substantial research with distressed couples and with 
technology-mediated interventions. In the event of an Adverse Event (AE), Serious Adverse 
Event (SAE), or Unanticipated Problem Involving Risks to Subjects or Others (UPR), all 
notification procedures outlined in the Data Safety and Monitoring Plan section will be followed.
Steps to protect against risk associated with intranasal oxytocin administration will be taken. 
During informed consent, participants will be informed about the potential side effects of 
intranasal oxytocin. Participants will not be enrolled unless the study psychiatrist, Dr. Maglione, 
concurs that no oxytocin-related exclusion criteria are met and the Veteran participant is eligible. 
Participants will self-administer intranasal oxytocin while being monitored on video by research 
staff who have ready access to clinicians who can consult on the need for emergency care, if 
necessary. They will be closely monitored by the research team after each drug administration. 
Women who are pregnant and lactating women will be excluded from the trial. We will instruct 
participants who are able to become pregnant to use appropriate forms of contraception, and we 
will instruct them to perform urine pregnancy tests at baseline and weekly during treatment 
before self-administration of oxytocin if a Veteran participant is considered able to become 
pregnant.
Numerous steps will be taken to protect against social risks related to confidentiality. Data will be 
identified via subject ID number only. The master list linking ID numbers to participants’ names 
will be stored locally on secure, restricted-access San Diego VA research servers in a password-
protected database only accessible on password protected computers. Only IRB-approved 
research staff that has completed training in the handling of confidential data, and re-trained at 
least once annually, will have access to participant data and files. Lastly, no individual or couple 
will ever be identified by name, audio recording, or other identifiers in professional presentations 
or manuscripts related to this study. Given the success of these measures in our previous 
research experience, we believe these procedures are extremely likely to be effective at 
minimizing the emotional and social risks to study participation.
 Section 17 - Potential Benefits
17) Discuss benefits that may be gained by the subject as well as potential benefits to society in general  (see  ?


for guidance)
Free access to B-CBCT is a benefit of participating. Specifically, participants may gain information 
that helps them to better understand and manage the affected partner’s symptoms of PTSD, as 
well as improve communication skills and relationship satisfaction for both members of the 
couple. Second, findings from the proposed study will inform whether B-CBCT social functioning 
outcomes can be improved with adjunctive medication. By potentiating the effects of B-CBCT 
with intranasal oxytocin, we could increase the clinical response rate of patients and their loved 
ones receiving B-CBCT. Third, if oxytocin enhances the mechanisms described in this proposal as 
predicted, it could further strengthen rationale for providers administering eight-session B-CBCT 
rather than 15-session CBCT. Effectively truncating CBCT would mean that more patients could 
be seen by the same number of VA providers, potentially improving Veterans’ access to 
treatment. Greater effectiveness and efficiency of treatment could lead to lower costs to the VA. 
Fourth, by targeting mechanisms that are salient not only to intimate relationships but all 
interpersonal relationships, such as trust, oxytocin could help the effects of B-CBCT extend to 
other, non-intimate relationships, thereby improving overall quality of life and potentially having 
downstream effects on other issues facing the VA (such as suicide, substance use, and co-
occurring disorders) which are known to be related to interpersonal difficulties. Lastly, improving 
Veterans’ social environments could help them maintain their gains and respond effectively to 
future stressors—potentially lowering the likelihood of future need for episodes of care.
 Section 18 - Risk/Benefit Analysis
18) Discuss why the risks to subjects are reasonable in relation to the anticipated benefits to subjects and in 
relation to the importance of the knowledge that may reasonably be expected to result.
Risk from participating in B-CBCT augmented with intranasal oxytocin is relatively minor in 
comparison with the potential benefits to relationship quality and PTSD symptoms to be gained 
by Veterans and their partners in this study, and is not anticipated to be any greater than risks 
they may encounter during standard clinical care. This investigation may help subjects manage 
the symptoms and functional impairment associated with PTSD and will provide valuable 
knowledge about the treatment of PTSD in Veterans. Furthermore, it may also help couples 
manage and improve relationship problems and associated functional impairment and will 
provide valuable knowledge about the treatment of relationship distress in Veterans with PTSD. 
Thus, the risk benefit ratio warrants this study being conducted.
This conclusion is supported further by the protection procedures in place to address any 
discomfort caused by the assessment or treatment to Veterans and partners. There is minimal 
risk associated with gathering information about emotional symptoms and taking part in a brief 
treatment for such symptoms based on an evidence-supported, manualized intervention. There 
are no aspects of this study that place participants at additional physical, psychological, social, 
legal or other risk outside of routine medical and mental health care. Risks associated with 
oxytocin consumption are mitigated by excluding pregnant women, conducting weekly pregnancy 
tests for Veteran participants who are able to become pregnant, and weekly questionnaire 
completion regarding any side effects of the oxytocin. Finally, we are mitigating the current risk 
of COVID-19 exposure by allowing participants to remain in their homes by using entirely virtual 
(telehealth, web, and phone) procedures for study enrollment and consent, intervention, and 
assessment. This study uses the existing VA telehealth infrastructure, including secure VVC 
telehealth appointments and Webex. 
Overall, the evaluation of a brief conjoint couple therapy for PTSD delivered via telehealth with 
adjunctive intranasal oxytocin appears to justify the identified risks involved in the treatment and 
assessment procedures in this study. This conclusion is supported further by the protection 
procedures in place to address any discomfort caused by the assessment or intervention to either 
the PTSD- affected individual or his/her intimate partner.
 Section 20 - Compensation for Participation
20) Provide all details and justifications of the compensation plan.  See  for detailed requirements.
?
Participants will receive up to $380 per couple for completing all assessment visits according to 
the following compensation plan: Baseline: $50 for the Veteran and $50 for the partner; Post-
treatment: $65 for the Veteran and $65 for the partner; and 3 month follow-up: $75 for the 
Veteran and $75 for the partner.


Payments will be made by direct deposit into the bank account of the couple’s choosing using 
electronic funds transfer. If the participant currently has a debt to the Federal Government, the 
debt may be subtracted from the funds transfer payment for study participation. 
Under 24 USC 30, payment to Federal Employees and Active Duty military personnel for 
participation in research while on duty is limited to blood donation and may not exceed $50. If 
the individual is a Federal Employee, it is understood that they may not receive any other 
payment or non-monetary compensation for participation on this research study unless they are 
off duty or on leave during the time they are participating in the research study.
 Section 21 - Responsibilities and Qualifications
Here are the identified study staff members
Leslie A. Morland, PsyD
Alex Lin, Amy Hoang, Lauren Maiko Grubbs, Katelyn D. Webster, MA, Jeanne E. Maglione, MD, 
PhD, Min Ji Sohn, Bette Chargin, Janina S. Schnitzer, BA, Julie M. Holcomb, Katerine T. 
Rashkovsky, Tamara Wachsman, Chandra E. Khalifian, PhD, Kayla C. Knopp, PhD, Cynthia 
Kerenyi, (ORO), Mark Borigini, (ORO), Monique Moxey, (ORO), Rachel Galvan, (ORO)
21) For each staff member listed above, describe their role and qualifications.  Also indicate which of the 
study staff are authorized to obtain consent, when applicable to the study. 
•Leslie A. Morland, PsyD, Principal Investigator: As project principal investigator (PI) based at 
the VA San Diego Healthcare System (VASDHS), Dr. Morland will supervise Ms. Webster in all 
aspects of this pilot research.
•Katelyn Webster, MA, Licensed Marriage and Family Therapist: Ms. Webster will conduct 
participant screening, obtain informed consent, deliver the CBCT intervention, and collect verbal 
feedback from participants.
•Jeanne Maglione, MD, PhD: Dr. Maglione will be the licensed prescriber of the oxytocin. She will 
assist with verifying eligibility for enrollment and monitoring of adverse events. 
•Min Ji Sohn: Ms. Sohn serves at the primary data manager and analyst, database builder and 
manager. She will assist in statistical analyses, methodological data collection concerns, and 
troubleshooting.
•Katerine Rashkovsky: Ms. Rashkovsky will aid with database management, obtaining informed 
consent, and other research administrative tasks.
•Tamara Wachsman: Ms. Wachsman will aid with database management, obtaining informed 
consent, and other research administrative tasks.
•Chandra Khalifian, PhD, research psychologist: Ms. Khalifian will deliver the CBCT intervention 
and aid with database management and analysis of data.
•Kayla Knopp, PhD, post-doctoral research fellow: Ms. Knopp will deliver the CBCT intervention 
and aid with database management and analysis of data.
•Volunteer Research assistants helping with day-to-day project tasks: Janina Schnitzer, Bette 
Chargin
 Section 22 - Bibliography
22) List relevant articles that the IRB can use to provide necessary background for the protocol. Do not 
include an extensive NIH-grant-style bibliography.  (Up to 5 recommended, but use more if needed to support 
the protocol or citations above.)
1. Monson, C. M., Fredman, S. J., Adair, K. C., Stevens, S. P., Resick, P. A., Schnurr, P. P., ... 
Macdonald, A. (2011). Cognitive-behavioral conjoint therapy for PTSD: Pilot results from a 
community sample. Journal of Traumatic Stress, 24(1), 97-101. doi:10.1002/jts.20604


2. Monson, C., & Taft, C. (2005). PTSD and intimate relationships. PTSD Research Quarterly, 16
(4), 1-7. Retrieved from https://search.proquest.com/docview/42415581?accountid=28179 
3. Morland, L. A., Macdonald, A., Grubbs, K. M., Mackintosh, M., Monson, C. M., Glassman, L. H., 
... Glynn, S. (2019). Design of a randomized superiority trial of a brief couple treatment for 
PTSD. Contemporary Clinical Trials Communications, 15, 100369. doi:10.1016/j.conctc.
2019.100369
4. Shnaider, P., Pukay-Martin, N., Fredman, S., Macdonald, A., & Monson, C. (2014). Effects of 
Cognitive-Behavioral Conjoint Therapy for PTSD on Partners’ Psychological Functioning. Journal 
of Traumatic Stress, 27(2), 129-136. doi:10.1002/jts.21893
5. Koch S, van Zuiden M, Nawijn L et al. Intranasal oxytocin as strategy for medication-enhanced 
psychotherapy of PTSD: Salience processing and fear inhibition processes. 
Psychoneuroendocrinology. 2014;40:242–56. 
6. Flanagan JC, Mitchell JM, Baker NL, et al. Enhancing prolonged exposure therapy for PTSD 
among veterans with oxytocin: Design of a multisite randomized controlled trial. Contemp Clin 
Trials. 2020;95:106074.
7. Ditzen B, Schaer M, Gabriel B, et al. Intranasal oxytocin increases positive communication and 
reduces cortisol levels during couple conflict. Biol Psychiatry. 2009;65:728–31. 
 Section 23 - Sponsors and Collaborators
23) Clarify any industry financial or other support (e.g., NIH funds the study or Company X provides the 
    
assay kits).
Identify non-VA Research collaborators and their role in this protocol, including whether or not 
 
they have access to subjects or identified data.
Sponsor: NCPTSD. This project is funded by NCPTSD using non-peer reviewed special project 
funds.
Non-VASDHS Research Collaborators:
Lauren Sippel, PhD: Dr. Sippel is an Assistant Professor in the Department of Psychiatry at the 
Geisel School of Medicine at Dartmouth, an Associate Director of the Northeast Program 
Evaluation Center at the VA Connecticut Healthcare System, and a practicing Psychologist at the 
White River Junction VA Medical Center. Her program of research focuses on delineating 
cognitive, affective, and neurobiological mechanisms of trauma recovery and interpersonal 
problems experienced by trauma-exposed individuals and developing novel treatments that 
target these shared mechanisms in an effort to improve social functioning. Dr. Sippel will consult 
on study design, conduct, and interpretation of data. Dr. Sippel will have access to de-identified 
data.
Julianne Flanagan, PhD: Dr. Flanagan is an Associate Professor in the Department of Psychiatry 
and Behavioral Sciences at the Medical University of South Carolina and a Staff Psychologist in 
the PTSD Clinical Team at the Ralph H. Johnson VAMC. Her program of research focuses on the 
behavioral and neurobiological mechanisms linking alcohol use with intimate partner aggression 
(IPA) and developing novel behavioral and pharmacological treatments for alcohol use disorders 
(AUD) in populations at high risk for IPA. Dr. Flanagan has extensive experience leading and 
collaborating on multidisciplinary projects in the area of Veterans’ health, PTSD, and complex 
comorbidities, with unique expertise in the conduct of trials of oxytocin-enhanced 
psychotherapies. She is currently the PI of two such trials, one a study of a couples intervention 
for alcohol use disorder augmented with oxytocin (funded by NIAAA) and the other a study of 
Prolonged Exposure for PTSD augmented with oxytocin among Veterans with PTSD (funded by 
VA CSRD). Dr. Flanagan will consult on study design, conduct, and interpretation of data. Dr. 
Flanagan will have access to de-identified data. 
Candice Monson, Ph.D., CBCT Consultant: Dr. Monson will provide consultation on the application 
of CBCT to Veteran couples. She is the lead developer of CBCT for PTSD and an expert in the 
couple-based PTSD treatment, as well as assessment of couple/family functioning. She is 
currently the PI on a NIH-funded RCT of CBCT for PTSD and has over 50 published articles 
related to PTSD. Dr. Monson will have access to de-identified data.
In the submission form, upload a copy of the grant, subaward, CRADA, etc. as appliable to the study.
 Section 27 - Privacy, Confidentiality, and Information Security


27a) Provide a brief description of how participant privacy and confidentiality will be protected in this study. 
Describe the circumstance under which it may be possible for a research team member to identify subjects 
and any related protections or assurances to prohibit or avoid identification. Describe how the number of 
people with access to identifiers for research purposes is limited in order to protect a participant’s privacy.
All study procedures will be approved and monitored by the VA San Diego’s IRB, which includes 
an annual audit of projects files, including informed consent audits. Monitoring of safety and data 
quality will be the responsibility of all personnel on the project, with primary responsibility and 
supervision by the PI. The PI will ensure that all research team members are properly trained in 
the reporting of AEs, SAEs, UPRs and protocol deviations, and follow the policies and procedures 
of the IRB. Any adverse effects noted by any project personnel in response to, or in potential 
response to, any project intervention, assessment protocol, or study involvement will be 
immediately reported to the PI. The procedures for notification include verbal notification of all 
levels of AEs and UPRs directly to the PI and documentation of the discussion and/or provision of 
a written notification or report to the PI through a case report form, sponsor communication, AE
/UPR reporting form, progress note, email or other method deemed acceptable by the PI. Any 
serious unanticipated adverse events or problems that may be related to the research will then 
be reported to the IRB within 5 business days. All other reports will be submitted at the time of 
the annual continuing review. Following each adverse event and in addition to the IRB 
determination, an investigation of the circumstances precipitating the event, all probable factors, 
the current status of the event, and the outcome of the event will be conducted by the project 
PI. A written summary of findings will be submitted to the IRB.
Any form of physical data containing PII (e.g., transcribed questionnaires) will be coded with 
research numbers that are matched to participant identifiers on a master list. This master list will 
be retained in a password-protected database on secure VA research servers accessible only on 
VA-networked password-protected computers. 
Electronic research data will include audio recordings of B-CBCT sessions as well as responses on 
self-report assessment surveys. Research data will be collected by hard copy or by phone and 
will be entered into an electronic data set stored on VA secure local research servers accessible 
only by authorized users on password-protected computers. 
In terms of participant safety monitoring, each participant will be given the telephone number of 
the PI and study clinician during the consenting process. Participants will be encouraged to call 
the PI or notify study staff if they experience significant distress from participating in the study. 
Any study staff will contact the PI about any participant who appears or reports significant 
distress related to study participation. All such participants will then be contacted personally by 
the PI and, in cases where the distress is extreme, the PI will decide upon and provide needed 
services or referrals. The study’s exclusion and inclusion criteria provide additional clinical 
safeguards by identifying appropriate participants for this treatment and excluding high risk 
patients (i.e., suicidal/homicidal ideation, domestic violence, active SUD, pregnancy
/breastfeeding, and hypertension).
This study will include a Data Safety and Monitoring Plan (DSMP) that will be developed in 
accordance with the National Institutes of Health (NIH) Office of Human Research Protection 
(OHRP) to assure the appropriate clinical safety monitoring of study subjects participating in this 
study. Recruitment and safety data are monitored according to the schedule established by the 
monitoring board, generally every 4-6 months for intervention studies. Quality control and 
assurance of data entered into the database is discussed above as part of Protections Against 
Risk. Missing data will be considered as part of the plan for statistical analysis. This study will not 
include a Data Safety Monitoring Board.
27.b) Entry of a CPRS 
is required when subjects will be 
 
Research Informed Consent Note
admitted as 
for research 
the study 
inpatients or treated as an outpatients 
 
and
involves research medical care or may affect 
medical care.
If a Research consent Note is required, then a 
 should also be entered for each 
Research Progress Note
procedure or intervention.
Scanning the Consent and HIPAA Authorization into CPRS is 
.  Linking the Consent to the 
not required
Research Informed Consent Note may be permitted and can be useful for trials involving the Research 
Pharmacy or when research will be performed in conjunction with clinical procedures.
For Non-Veterans, if Research Informed Consent Notes are entered, then the 
 
NOPP Acknowledgment
must be scanned into the record.  Otherwise a copy of the signed NOPP must be retained with the 
Investigator's research records and a copy sent to the Privacy Officer; see the   Help for more information.
 ?


27.b1) Is entry of CPRS notes required based on the above criteria?
CPRS notes are needed for ALL subjects 
CPRS notes are needed for SOME subjects 
CPRS notes are NOT needed for any subjects 
Identify for which group or groups CPRS records will be entered and to which groups this requirement does not 
apply.
CPRS records will be entered for VA-enrolled Veteran subjects. Information to open a collateral 
medical record will be collected but will not be opened unless clinical need arises (e.g., disclosure 
of suicidality). If no clinical need arises, CPRS notes will not be entered for non-veteran subjects.
27c) Select the VA Sensitive Information (VASI) use category
This study does not collect or use any VASI 
This study uses but does not save, collect, copy, or record VASI 
This study does collect or record VASI 
 Section 27.1  VA Sensitive Information (VASI)
27.1a) For each type of VASI, indicate all that apply:
Indicate which of the following will be collected/recorded:
Protected Health Information (PHI)
Names
Device identifiers and serial numbers
E-mail addresses
Medical record numbers
URLs (Universal Resource Locator)
All elements of dates (except year) or any age over 89
Health plan beneficiary numbers
IP Addresses (Internet Protocol)
Telephone numbers
Account numbers
Biometric Identifiers including finger and voice print
Fax numbers
Certificate or license numbers
Full face photographic images and comparable images
All geographic subdivisions smaller than a state
Vehicle ID and serial numbers including license plate numbers
Social security numbers or scrambled SSNs (describe below)
Other unique identifying number, characteristic, or code (describe below)
27.1a1)  Describe why SSN are needed for this study
Subject payment and use of clinical record.
27.1a2)  Identify the specific other identifier/s that will be used or recorded
Date of birth for non-veteran partners. We must collect this in order to complete the form for 
opening a collateral medical record for non-veterans, in case doing so is needed to document a 
safety concern or other non-veteran partner information.


27.1b) Consent Forms and/or HIPAA Authorization
 Yes  
 No
27.1c) Images with personal identifiers are used for this study (x-rays, MRI images with patient names, record 
numbers, dates, etc.)?
  Yes  
  No
27.1d) Photos with faces or audio video recordings are used for this study.
 Yes  
 No
27.1d1) Identify the device or devices that will be used to take/make the photographs or recordings. 
Audacity
27.1d2) Identify where images will be stored (e.g., in the medical record, with study hardcopy records, with 
study electronic VASI records
The study will collect audio recordings of patient-therapist meetings and assessments. These 
recordings are considered PHI under HIPAA and VA definition of PHI. These audio recordings will 
be collected using Audacity. The audio recordings will be saved directly to a secure VA share 
drive and labelled with anonymous study subject IDs. Only study personnel will have access to 
the audio recordings. A VA-approved USB microphone that is not capable of storing any data on 
it will be used to enhance the sound quality. Audio-recordings will be deleted when permitted 
pursuant to the VA Record Retention Schedule.
27.1e) Biological specimens with identifiers are used for this study.
  Yes  
  No
 Section 27.2  Data Collection, Tools, and Resources
27.2a)  Will any specially obtained software be used?
  Yes  
  No
27.2b) Will any mobile devices (laptop, tablet, portable hard-drive, etc.) be used in support of this study?
  Yes  
  No
27.2c) Does the study require use of an electronic data capture system? 


  Yes  
  No
27.2d) Will any other web-based applications be used (e.g., for recruitment, completing online questionnaires, 
or processing data)?
  Yes  
  No
27.2e)  Will coded data that excludes personal identifiers be used?   Coded data excludes 
HIPAA identifiers 
all 
(per VHA Handbook 1605.1 Appendix B), including dates
 Yes  
 No
27.2e1) Identify where the code key is stored and in what format (electronic, paper).
Electronically in an Access database on a secure VA research server accessible only on VA-
networked password-protected computers.
 Section 27.3  Data Sharing and Transportation
27.3a) Does this study involve collecting, sharing or transporting any type of data outside of the local VA?
 Yes  
 No
27.3b) This study collects VASI outside of VA (i.e., at a non-VA location).
 Yes  
 No
27.3b1) Describe what is collected outside the VA and how it is secured in transit back to the VA. Note: An 
approved Authorization to Transport will be required.
Clinical contact is provided to Veteran’s homes via VA Video Connect, VA's secure clinical video 
telehealth system, and Webex.
27.3c) VASI is transported outside of VA for any purpose other than sharing.
  Yes  
  No
27.3d) PHI may be disclosed to monitoring/auditing agencies by HIPAA Authorization.  Note:  The Research 
Office must be notified when monitors come to audit


 Yes  
 No
27.3e) Data may be shared with collaborators or others in the conduct of this protocol.
 Yes  
 No
27.3e1)  Describe the data to be shared or disclosed, the entities to which the data are to be disclosed, how the 
data are to be transmitted, and how the transmitted data will be stored, retained, destroyed, and/or further 
disclosed and to whom. This includes data from individual subjects as well as other data developed during the 
research such as the analytic data and the aggregate data.  For PHI and VASI, indicate the authority/ies 
permitting the sharing or disclosure of data (HIPAA Authorization, Limited Data Set, Data Use Agreement, VA 
Form 10-5345-Request for and Authorization to Release Health Information., etc.).
In general, it is unlikely that de-identified study data will be sent to collaborators. On the rare 
occasion that de-identified data is shared with collaborators, an Excel database would be stripped 
of identifiers other than the subject ID. The data sets will not contain any of the 18 HIPAA 
personal identifiers, and collaborators will not have access to linkage information. This Excel 
database would include baseline and outcome self-report measures data and would be shared for 
the purpose of descriptive and/or differential analysis. The files would be sent via encrypted 
email and would be password protected. The passwords would then be sent in a separate email 
to ensure security.
 
Section 27.4  Research Record Storage and Retention
For each type of record, indicate whether it is collected for this study
27.4a) Hardcopy records/data (includes paper, pictures, film, etc.)
 Yes  
 No
27.4a1) Identify precisely where hardcopy data will be stored to include physical site, building, and room 
number, etc.  For each location identify whether VASI or non-sensitive information is stored at that 
location.  For VASI, identify how the data is secured. 
Physical VASI records will be kept in locked cabinets in a locked office (room 418) in Building 13 
at the Veterans Medical Research Foundation. Data will be retained in accordance with VA record 
control schedule RCS 10-1.
27.4a2) Are all of the above locations at VA?
 Yes  
 No
27.4b) Electronic study records (includes computer files, removable disk files, digital files, etc.).
 Yes  
 No
27.4b1) Identify precisely where 
electronic records/data will be stored to include the full map 
 
non-sensitive
drive, network location/server name, etc., and a brief description of what data/information is stored at each 
location.


S Drive; PI folder: Morland
Assessment measures, recruitment materials, consent documents, etc.
27.4b2) Identify precisely where 
electronic records/data will be stored to include the full map drive, 
 
VASI
network location/server name, etc., and a brief description of what data/information is stored at each location.
If no VASI is collected or recorded for this study, simply indicate that the “Study does not collect or record 
VASI”.
S Drive; PI folder: Morland
Names, phone numbers, last 4, and addresses are stored in an encrypted file at the location 
listed above.
27.4b3) Are any of the locations described in 27.4b outside of the VA Secure Network? Note: this includes 
storage on a computer local hard drive.
  Yes  
  No
27.4c)  Record Retention - VHA requires compliance with Records Control Schedule (RCS-10) for retention 
of electronic and hard copy records.  Following study closure, these temporary records must be retained 
for six years and then destroyed.  Longer retention may be permitted if requred by other Federal regulations 
or requirements.  Will RCS-10 requirements be followed (i.e., 6-year retention)?
I will adhere to VHA Records Control Schedule-10 requirements 
I request an exception to RCS-10 requirements 
 Section 27.5  Additional Privacy or Information Security Details
Provide any other privacy or information security details here.
NA
 Section 27.6  Attestations
In the event of real or suspected breach of security, the Information Security Officer, Privacy Officer, VA 
Police (if appropriate), and the individual’s supervisor will be notified within one hour of learning of the event.
 Agree
 Disagree
Study staff will be up to date on any required VHA Privacy Policy and Information Security training or they 
will not be allowed access to VA Sensitive Information.
 Agree
 Disagree
Access to research sensitive information, if any, will be removed when study personnel are no longer part of 
the research team.
 Agree
 Disagree
At least one copy of all study records (whether sensitive or non-sensitive) will be retained under VA control 
and only destroyed in compliance with the approved Records Control Schedule


 Agree
 Disagree
The VA retains ownership of the research data.  Should the investigator leave the VA, custody of the research 
records will be assigned to another investigator and the Research Service notified in writing, or custody of the 
research records will be transferred to the Research Service.
 Agree
 Disagree
 Section 28 - Protocol Association to New or Existing Project
  
28) Is this a new R&D Project?  Before you go on to complete the 
 (which is 
Initial Review Submission Form
used for attachments), please address the association of this Protocol to an R&D Committee Project.  This 
Protocol may represent a new R&D Project, or it may be an additional Protocol under an existing R&D 
  
Project (such as when a single grant supports multiple Protocols).  Will this Protocol be submitted to the 
R&D Committee as a new Project?
 Yes  
 No
 The Protocol Application is now complete for a Protocol that will also be a new R&D Committee 
Project.
 
Next you will go on to the Initial Review Submission Form which is used to package up the Protocol 
Application and any needed attachments and submit them to the IRB.
Click on Save and Continue

SAP_001.pdf: 
 
Brief Cognitive Behavioral Conjoint Therapy for PTSD With Adjunctive Intranasal Oxytocin 
(CBCT+OT) 
 
NCT05207436 
 
2/15/23 
 
Data Analytic Plan 
Primary analyses with the intent-to-treat sample evaluated change in PTSD symptoms 
and relationship satisfaction using weekly session, baseline, and post-treatment data analyzed 
with multilevel linear growth models in the R package lme4 and a Kenward-Roger small samples 
correction. To account for dyadic interdependence, time was nested within individuals and 
individuals were nested within couples. Analyses included two-intercept models, which produce 
separate slope and intercept estimates for PTSD+ veterans and non-PTSD+ partners, and a 
separate interaction model to test for differences between slope and intercept estimates for 
veterans and partners. PTSD data was composed of veteran PCL-5 and partner/collateral PCL-5 
scores. Relationship satisfaction data were CSI-4 scores for both partners; at baseline and post-
treatment, the four items comprising the CSI-4 were extracted from the CSI-32 to be included in 
growth curve analyses.