Oxytocin Nasal Spray for PTSD

(CBCT-OT RCT Trial)

Overseen By Leslie A. Morland, PsyD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Disqualifiers: Substance dependence, Psychotic disorder, Borderline personality, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

240 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires that you have been on a stable psychoactive medication regimen for at least 2 months, so you do not need to stop your current medications if they are stable.

What data supports the effectiveness of the drug oxytocin nasal spray for PTSD?

Research suggests that oxytocin nasal spray may help reduce PTSD symptoms, especially when used early after trauma or combined with therapy. Studies have shown it can improve treatment outcomes and relationship satisfaction in veterans with PTSD. ^{1 2 3 4 5}

How does oxytocin nasal spray differ from other PTSD treatments?

Oxytocin nasal spray is unique because it delivers oxytocin directly to the brain, which may help reduce PTSD symptoms by affecting brain areas involved in fear and social behavior. This method is different from other treatments as it uses a nasal spray to target the brain more directly, potentially offering a new way to manage PTSD symptoms. ^{1 3 5 6 7}

What is the purpose of this trial?

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.

Research Team

Leslie A. Morland, PsyD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Lauren M. Sippel, PhD

Principal Investigator

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Eligibility Criteria

This trial is for veterans with PTSD who are in a relationship. It's designed to help improve both their PTSD symptoms and relationship quality. Participants must be willing to undergo couples therapy and use either an oxytocin or saline nasal spray.

Inclusion Criteria

I have been on the same mental health medication for at least 2 months.

I am a veteran over 18 with PTSD diagnosed at least 3 months after my trauma.

I am over 18 and willing to join the study but I don't have PTSD.

Exclusion Criteria

Imminent suicidality or homicidality in either member of the couple

Positive screen (7+) for borderline personality disorder (BPD) in either member of the couple as assessed by the MacLean Screening Instrument for BPD

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)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly, with either intranasal oxytocin or placebo administered prior to each session

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at mid-treatment, post-treatment, 3-month, and 6-month intervals

6 months

Treatment Details

Interventions

• Intranasal Oxytocin

Trial Overview The study tests if adding oxytocin nasal spray to brief couples therapy (bCBCT) is more effective than just the therapy with a saline placebo. The goal is to see if this combination can better treat PTSD and enhance relationship satisfaction among veterans.

Participant Groups

Group I: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Oxytocin Experimental Treatment 2 Interventions

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

Group II: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal Placebo Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Intranasal oxytocin is a promising, low-cost treatment option for posttraumatic stress disorder (PTSD) with a strong safety profile, especially when combined with established psychotherapy methods.

Current research suggests that while oxytocin may enhance treatment outcomes for PTSD and related substance use disorders, further studies are needed to understand its mechanisms of action and optimize delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmenting Treatment for Posttraumatic Stress Disorder and Co-Occurring Conditions with Oxytocin. Flanagan, JC., Mitchell, JM.[2022]

A pilot study involving 10 U.S. veterans with PTSD and their partners showed that combining brief Cognitive-Behavioral Conjoint Therapy (bCBCT) with intranasal oxytocin led to significant improvements in relationship satisfaction and PTSD symptoms, with no serious adverse events reported.

Veterans experienced a large reduction in PTSD severity (effect size of 1.87), while both partners reported moderate to large improvements in relationship satisfaction, indicating that this approach is feasible and may enhance the effectiveness of traditional therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot test of intranasal oxytocin as an enhancer of brief couples therapy for posttraumatic stress disorder. Sippel, LM., Khalifian, CE., Knopp, KC., et al.[2023]

A multicenter randomized controlled trial involving 107 trauma-exposed patients showed that repeated intranasal oxytocin administration significantly reduced the development of PTSD symptoms up to six months after trauma, particularly in those with high acute PTSD symptoms.

Functional MRI studies indicated that a single dose of oxytocin increased amygdala reactivity to fearful stimuli, suggesting that while oxytocin may initially heighten fear responses, its repeated use can help mitigate long-term PTSD risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals. Frijling, JL.[2020]

This Phase II study aims to evaluate the effectiveness of intranasal oxytocin combined with Prolonged Exposure (PE) therapy in reducing PTSD symptoms among U.S. military veterans, using a randomized, double-blind, placebo-controlled design.

The study will assess not only the reduction in PTSD symptom severity but also the rate of improvement and retention in therapy, providing insights into how oxytocin may enhance the effectiveness of existing PTSD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. Flanagan, JC., Mitchell, JM., Baker, NL., et al.[2021]

Oxytocin (OXT) can be effectively delivered to the brain through nasal administration, achieving higher brain concentrations compared to intravenous delivery, despite lower plasma levels.

The study found that the nasal bioavailability of OXT is approximately 2%, and its therapeutic effects, such as stress relief, were observed only after intranasal application, highlighting the potential of this route for treating conditions like autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application. Tanaka, A., Furubayashi, T., Arai, M., et al.[2019]

In a study of 13 participants with PTSD, baseline levels of peripheral oxytocin did not correlate with the severity of PTSD symptoms, suggesting that oxytocin levels may not be a reliable biomarker for PTSD severity.

The study found that changes in peripheral oxytocin levels after treatment did not differ between those receiving intranasal oxytocin and those receiving a placebo, indicating that oxytocin administration may not directly influence PTSD symptom improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Preliminary Examination of Endogenous Peripheral Oxytocin in a Pilot Randomized Clinical Trial of Oxytocin-Enhanced Psychotherapy for Posttraumatic Stress Disorder. Sippel, LM., King, CE., Wahlquist, AE., et al.[2022]

Intranasal administration of oxytocin (OT) effectively increases its concentration in the cerebrospinal fluid (CSF) and plasma, suggesting it can reach central nervous system targets.

Both delivery methods (intranasal spray and nebulizer) were effective in elevating CSF OT levels, with the nasal spray showing greater increases in plasma OT concentration compared to the nebulizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CSF and blood oxytocin concentration changes following intranasal delivery in macaque. Dal Monte, O., Noble, PL., Turchi, J., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Augmenting Treatment for Posttraumatic Stress Disorder and Co-Occurring Conditions with Oxytocin. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pilot test of intranasal oxytocin as an enhancer of brief couples therapy for posttraumatic stress disorder. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

A Preliminary Examination of Endogenous Peripheral Oxytocin in a Pilot Randomized Clinical Trial of Oxytocin-Enhanced Psychotherapy for Posttraumatic Stress Disorder. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

CSF and blood oxytocin concentration changes following intranasal delivery in macaque. [2021]