Recruiting
Phase 2

Oxytocin

Sponsor:

VA Office of Research and Development

Code:

NCT06194851

Conditions

Post-Traumatic Stress Disorder (PTSD)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Oxytocin nasal spray

Saline nasal spray

Brief Cognitive-Behavioral Conjoint Therapy

Study Details

Brief summary:

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.

Conditions

Post-Traumatic Stress Disorder (PTSD)

Study ID

NCT06194851

Start date

Oct 28, 2024

Status verified date

Apr, 2026

Completion date

Sep 30, 2028

Anticipated

Primary completion date

Sep 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Inclusion criteria for Veteran:

1. Be a Veteran (age 18 or older) with a current DSM-5 diagnosis of PTSD (as assessed by the CAPS-5 with a minimum severity score of 25) 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 4 weeks (if applicable)
3. Be enrolled and eligible to receive care at the VASDHS

Inclusion criteria for Partner:
4. 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 Veteran and Partner:
5. Be married, or cohabitating for at least 6 months
6. Willing to be randomized into either treatment condition (bCBCT + OT or bCBCT + PL)
7. Agree to have assessment and treatment sessions audio/video recorded
8. Agree not to receive other individual trauma-focused psychotherapy for PTSD or any form of conjoint therapy during the treatment portion of the study
9. Have the capacity to participate in virtual care (access to internet via DSL or a cable provider, private space)

Exclusion Criteria:

Exclusion criteria for Veteran and Partner:
10. 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)74 and Drug Abuse Screening Test (DAST)75
11. Any current uncontrolled psychotic disorder in either member of the couple as assessed by positive screen on the Prime Screen-Revised (PS-R). Exclusion to be determined following case consult by PI or other clinician.
12. Imminent suicidality or homicidality in either member of the couple (e.g., C-SSRS)
13. Any severe cognitive or medical impairment in either member of the couple making it difficult to regularly attend weekly couples psychotherapy
14. 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 Veteran:
15. Severe ongoing medical problems, including heart disease, uncontrolled hypotension (systolic blood pressure <100 mm Hg) or hypertension (systolic BP >130 or diastolic BP > 80 mm Hg), and neuroendocrinological disorders (e.g., diabetes). Exclusion to be determined in collaboration with study physician following completion of physician's one-on-one appointment with Veteran and review of all relevant information (e.g., risk factors, health history, concomitant medications, etc.) from Veteran's VA medical record and study screening/assessment processes including selfreport measures and blood pressure measurement. Additionally, Veterans for whom the study physician has elevated concern, will be asked to attend an in-person visit at a VA medical center, clinic, or the Veterans Medical Research Foundation before enrollment.
16. Positive screen (7+) for borderline personality disorder (BPD) as assessed by the MacLean Screening Instrument for BPD76. Exclusion to be determined following case consult by PI or other clinician.
17. Pregnancy, delivery in the past 6 months, current breastfeeding, or the ability to become pregnant while not practicing an effective method of contraception. If able to become pregnant, Veteran must have a highly sensitive negative urine pregnancy test verified visually via telehealth or in-person at the Veterans Medical Research Foundation by research staff at study entry and prior to each medication administration during treatment. Veteran must verbally confirm that they completed the test themselves that day. Veteran must also agree to use an effective birth control method from study entry until conclusion of treatment to prevent pregnancy. The ability to become pregnant is defined as: assigned female at birth, fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

Effective birth control methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, oral hormones, a barrier contraception method (e.g., male or female condoms, diaphragm, cap), or vasectomized sole sexual partner.

Pregnancy tests will be purchased by the study and mailed to Veteran unless PI has approved waiver of testing requirement.
18. Known allergy to preservatives (i.e., Methylparaben, Propylparaben, Glycerin, Sodium Benzoate, Potassium Sorbate, and Disodium EDTA) utilized in oxytocin nasal spray.

Study Design

Enrollment

240 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

Interventions

Oxytocin nasal spray

Veteran participants will self-administer 40 IU of intranasal oxytocin 30 minutes before the start of each bCBCT session.

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.

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.

Primary outcome measure

  • PTSD diagnosis and severity change [ Time Frame: Baseline - 6-months post treatment ]

Central Contacts and Locations

Central contacts

Locations

VA San Diego Healthcare System, San Diego, CA

Recruiting

San Diego, California, United States, 92161-0002

Contacts

Principal Investigator:

Leslie A. Morland, PsyD

More Information

Sponsor

VA Office of Research and Development

Last update posted

May 4, 2026

Last verified

Apr, 2026

Keywords

  • Post Traumatic Stress Disorder (PTSD)
  • Oxytocin
  • Relational Problems
  • Brief Cognitive Behavioral Conjoint Therapy
  • Veterans

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-05-04.