Examining Intranasal Oxytocin Augmentation of Brief Couples Therapy for Veterans With PTSD (CBCT-OT RCT)

A Randomized Clinical Trial Examining Intranasal Oxytocin Augmentation of Brief Couples Therapy for Veterans With PTSD

Leveraging veterans' intimate relationships during treatment for posttraumatic stress disorder (PTSD) has the potential to concurrently improve PTSD symptoms and relationship quality. Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) is a manualized treatment designed to simultaneously improve PTSD and relationship functioning for couples in which one partner has PTSD. Although efficacious in improving PTSD, the effects of CBCT on relationship satisfaction are small, especially among Veterans. Pharmacological augmentation of bCBCT with intranasal oxytocin, a neurohormone that influences mechanisms of trauma recovery and social behavior, may help improve the efficacy of bCBCT. The purpose of this randomized placebo-controlled trial is to compare the clinical and functional outcomes of bCBCT augmented with intranasal oxytocin (bCBCT + OT) versus bCBCT plus placebo (bCBCT + PL). The investigators will also explore potential mechanisms of action: communication, empathy, and trust.

Study Overview

• Status: Not yet recruiting
• Conditions: Post-Traumatic Stress Disorder (PTSD)
• Intervention / Treatment: Drug: Oxytocin nasal spray; Behavioral: Brief Cognitive-Behavioral Conjoint Therapy; Drug: Saline nasal spray

Detailed Description

The primary aim of this study is to investigate the effects of Brief Cognitive Behavioral Conjoint Therapy (bCBCT) paired with intranasal oxytocin (OT) versus placebo on PTSD symptoms, intimate relationship satisfaction and psychosocial functioning in a sample of veterans with PTSD (across all measures) and their intimate partners (relationship satisfaction only). The study will also explore the impact of intranasal oxytocin on potential mechanisms of action (i.e., communication skills, empathy, and trust).

bCBCT is a modified PTSD-specific cognitive-behavioral psychotherapy attended by the couple that uses close relationships as the vehicle for recovery. Across eight 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.

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. 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 among clinical samples are needed.

The investigators will employ a double blind, placebo-controlled RCT design in which Veterans will receive a dose of oxytocin or placebo before each bCBCT session and complete mid-treatment, post-treatment, 3-month, and 6-month follow-up assessments. Based on the findings from past bCBCT trial and the investigators' recent bCBCT + OT pilot study, the investigators anticipate about 1/3 of the sample will be dual Veterans or the identified Veteran is female. The investigators project an approximate 20-25% attrition rate, resulting in approximately 100 couples completing treatment. Consistent with past trials, to enhance retention, the investigators will ask couples to provide contact information for collateral informants who can reach them if the investigators are unable to do so via their primary contact information. Study personnel will routinely remind couples of appointments via telephone and/or letters and the team will meet weekly to review and problem-solve retention strategies. These are all established procedures implemented from successful prior trials. If successful, the study will advance knowledge of strategies for improving Veterans' quality of life by improving their intimate relationships along with PTSD symptoms.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Leslie A Morland, PsyD; Phone Number: (619) 497-8406; Email: Leslie.Morland@va.gov
• Study Contact Backup: Name: Lauren M Sippel, PhD; Phone Number: (802) 291-2394; Email: Lauren.Sippel@va.gov

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161-0002
      • VA San Diego Healthcare System, San Diego, CA
      • Contact: Patricia A Franklin, AA BS; Phone Number: 7441 858-552-8585; Email: patricia.franklin2@va.gov
      • Principal Investigator: Leslie A. Morland, PsyD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion criteria for Veterans

1. Be a veteran (age 18 or older) with a current DSM-5 diagnosis of PTSD (as assessed by the CAPS-5) no less than 3 months after the index trauma occurred (to allow for potential natural recovery)
2. Be on a stable psychoactive medication regimen for at least 2 months (if eligible)
3. Veteran must be enrolled and eligible to receive care at the VASDHS

Inclusion criteria for Partners

1.Be an intimate partner (age 18 or older) who is willing to participate in the intervention (partners can also be veterans but cannot meet criteria for possible PTSD per the PCL-5)

Inclusion criteria for Veterans and Partner dyads

1. Be married, or cohabitating for at least 6 months
2. Willing to be randomized into both treatment conditions
3. Agree to have assessment and treatment sessions audio recorded
4. Agree not to receive other individual or conjoint trauma-focused psychotherapy for PTSD during the treatment portion of the study
5. Have the capacity to participate in virtual care (access to internet via DSL or a cable provider, private space)

Exclusion Criteria:

Exclusion criteria for Veterans and Partners

1. Current substance dependence in either member of the couple not in remission for at least 3 months, as assessed by the Alcohol Use Disorders Identification Test (AUDIT) and Drug Abuse Screening Test (DAST)
2. Any current uncontrolled psychotic disorder in either member of the couple as assessed by the SCID-5 psychosis module
3. Positive screen (7+) for borderline personality disorder (BPD) in either member of the couple as assessed by the MacLean Screening Instrument for BPD
4. Imminent suicidality or homicidality in either member of the couple
5. Any severe cognitive or medical impairment in either member of the couple making it difficult to regularly attend weekly couple's psychotherapy
6. Any perpetration of severe physical or sexual relationship aggression (as assessed by the CTS-2) or fear/intimidation (3-item IPV screen, Couples Questionnaire) in the past year

Exclusion criteria for Veterans with PTSD:

1. Severe ongoing medical problems, including heart disease and neuroendocrinological disorders (e.g., diabetes)
2. Uncontrolled hypotension (systolic blood pressure <100 mm Hg) or hypertension (BP >160/100 mm Hg) as assessed by self-report and verified with VA chart review (in absence of chart documentation in past month, participant will be sent digital BP device and cuff to verify BP stability during video monitoring)
3. Pregnancy, delivery in the past 6 months, or current breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Oxytocin; Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly. Prior to each session, the veteran participant will self-administer intranasal oxytocin.	Drug: Oxytocin nasal spray; Veteran participants will self-administer 40 IU of intranasal oxytocin 30 minutes before the start of each bCBCT session.; Other Names: Pitocin; Behavioral: Brief Cognitive-Behavioral Conjoint Therapy; Eight sessions of standardized bCBCT, a manualized couple-based intervention for PTSD designed to simultaneously reduce PTSD and enhance relationship and functioning.; Other Names: bCBCT
Placebo Comparator: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Placebo; Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly. Prior to each session, the veteran participant will self-administer intranasal placebo solution.	Behavioral: Brief Cognitive-Behavioral Conjoint Therapy; Eight sessions of standardized bCBCT, a manualized couple-based intervention for PTSD designed to simultaneously reduce PTSD and enhance relationship and functioning.; Other Names: bCBCT; Drug: Saline nasal spray; Veteran participants will self-administer 40 IU of the placebo (intranasal saline spray) 30 minutes before the start of each bCBCT session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTSD diagnosis and severity change	The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 20-item diagnostic interview administered by trained evaluators to assess PTSD in a participant. Based on DSM-5 diagnostic criteria, evaluators ask about the severity of four PTSD-related symptom clusters: re-experiencing, avoidance, negative alterations in cognition and mood, and alterations in arousal and reactivity. The evaluator rates responses on a 5-point Likert scale (0 = Absent to 4 = Extreme/Incapacitating). Total scores range from 0 to 80 with higher scores indicating greater severity. CAPS-5 will be completed by veterans with PTSD only.	Baseline - 6-months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship satisfaction	The Couples Satisfaction Index (CSI-32). The CSI-32 is a 32-item self-report survey that measures romantic relationship satisfaction. The first item measures the overall happiness of the relationship on a 7-point scale (0 = Extremely unhappy to 6 = Perfect). The other 31 items capture satisfaction, quality, and happiness of the relationship on 6-point scales (0 to 5) with varying response options. Total CSI-32 scores range from 0 to 161 with higher scores indicating greater relationship satisfaction. Scores below 104.5 indicate clinical relationship distress. CSI-32 will be completed by both partners.	Baseline - 6-months post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychosocial functioning	The Brief Inventory of Psychosocial Functioning (B-IPF) is a brief version of the Inventory of Psychosocial Functioning (IPF) that measures functioning impairment across seven domains: intimate relationships, family and parenting, friendships, work, socializing, education, and self-care over the past 30 days. Total scores, ranging from 0 to 100, are calculated as the sum score divided by the total possible score multiplied by 100, with higher scores indicating greater impairment in functioning. B-IPF will be completed by veterans with PTSD only.	Baseline - 6-months post treatment
Trust	The Trust in Close Relationships Scale (TCRS) is a 17-item self-report measure of trust in close relationships, including predictability, dependability, and faith in close others. The TCRS uses a 7-point Likert scale (-3 = Strongly Disagree to 3 = Strongly Agree) to capture one's level of trust in their intimate partner. Total TCRS scores range from -51 to 51, with higher scores indicating higher levels of trust. The TCRS will be completed by both partners.	Baseline - 6-months post treatment
Empathy	The Interpersonal Reactivity Index for Couples (IRIC) is a measure of empathy expressed within romantic relationships. The IRIC is a 28-item self-report assessment in which participants select their responses to each item on a 5-point Likert scale (0 = does not describe me well to 4 = describes very well). Items are divided into four subscales with 7 items each: perspective-taking, fantasy, empathic concern, and personal distress. Total scores on the IRIC range from 0 to 112 with higher scores indicating higher empathy. This measure will be completed by both partners.	Baseline - 6-months post treatment
Communication	The Brief Communication Skills Test (CST) is a self-report measure of communication skills that was created by pulling the positive communication questions from the full CST. Participants rate items on a 7-point scale from 1 (Almost Never) to 7 (Almost Always). Total scores range from 10 to 70, with higher scores indicating more positive communication. This will be completed by both partners.	Baseline - 6-months post treatment

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Leslie A. Morland, PsyD, VA San Diego Healthcare System, San Diego, CA; Principal Investigator: Lauren M. Sippel, PhD, VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Study record dates

Study Major Dates

• Study Start (Estimated): September 2, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: December 22, 2023
• First Posted (Actual): January 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Veterans; Oxytocin; Post Traumatic Stress Disorder (PTSD); Relational Problems; Brief Cognitive Behavioral Conjoint Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: D4776-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes