Examining Intranasal Oxytocin Augmentation of Brief Couples Therapy for Veterans With PTSD

NCT06194851 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: D4776-R
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

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)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Relationship satisfaction

  Baseline - 6-months post treatment

Other Outcomes (4)

• Psychosocial functioning

  Baseline - 6-months post treatment

• Trust

  Baseline - 6-months post treatment

• Empathy

  Baseline - 6-months post treatment

Study Arms (2)

Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Oxytocin

EXPERIMENTAL

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; Behavioral: Brief Cognitive-Behavioral Conjoint Therapy

Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Placebo

PLACEBO COMPARATOR

Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly. Prior to each session, the veteran participant will self-administer intranasal placebo solution.

Drug: Saline nasal spray; Behavioral: Brief Cognitive-Behavioral Conjoint Therapy

Interventions

Oxytocin nasal spray DRUG

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

Also known as: Pitocin

Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Oxytocin

Saline nasal spray DRUG

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 for PTSD plus Intranasal Placebo

Brief Cognitive-Behavioral Conjoint Therapy BEHAVIORAL

Eight sessions of standardized bCBCT, a manualized couple-based intervention for PTSD designed to simultaneously reduce PTSD and enhance relationship and functioning.

Also known as: bCBCT

Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Oxytocin; Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Be on a stable psychoactive medication regimen for at least 4 weeks (if applicable)
• Be enrolled and eligible to receive care at the VASDHS
• 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)
• Be married, or cohabitating for at least 6 months
• Willing to be randomized into either treatment condition (bCBCT + OT or bCBCT + PL)
• Agree to have assessment and treatment sessions audio/video recorded
• Agree not to receive other individual trauma-focused psychotherapy for PTSD or any form of conjoint therapy during the treatment portion of the study
• Have the capacity to participate in virtual care (access to internet via DSL or a cable provider, private space)

You may not qualify if:

• 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
• Imminent suicidality or homicidality in either member of the couple (e.g., C-SSRS)
• Any severe cognitive or medical impairment in either member of the couple making it difficult to regularly attend weekly couples psychotherapy
• 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
• 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.
• Known allergy to preservatives (i.e., Methylparaben, Propylparaben, Glycerin, Sodium Benzoate, Potassium Sorbate, and Disodium EDTA) utilized in oxytocin nasal spray.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

RECRUITING

Related Publications (1)

• Sippel LM, Wachsman TR, Kelley ME, Knopp KC, Khalifian CE, Maglione JE, Glynn SM, Macdonald A, Monson CM, Flanagan JC, Holtzheimer PE, Morland LA. Design of a randomized clinical trial of brief couple therapy for PTSD augmented with intranasal oxytocin. Contemp Clin Trials. 2024 Jun;141:107534. doi: 10.1016/j.cct.2024.107534. Epub 2024 Apr 12.

  PMID: 38614447 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leslie A Morland, PsyD

CONTACT

(619) 497-8406; Leslie.Morland@va.gov

Lauren M Sippel, PhD

CONTACT

(802) 291-2394; Lauren.Sippel@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, quadruple masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Eligible dyads will be randomized in a stratified 1:1 manner to the oxytocin or placebo condition.

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 8, 2024
• Study Start: October 28, 2024
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)