Oxytocin for PTSD

No longer recruiting at 1 trial location

Overseen By Julianne Christina Flanagan, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: Psychotropic medications

Must not be taking: Anxiolytics, Antidepressants, Mood stabilizers

Disqualifiers: Psychotic, Bipolar, Suicidal, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether oxytocin, a hormone, can enhance Prolonged Exposure (PE) therapy for Veterans with PTSD. The researchers aim to determine if oxytocin can reduce PTSD symptoms, accelerate symptom relief, and improve therapy adherence. The study compares oxytocin with a placebo (a non-active treatment) and can be conducted from home using video calls. Veterans diagnosed with PTSD in the last six months and stable on any required medications might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering Veterans a chance to contribute to important findings.

Do I have to stop taking my current medications for the trial?

You don't have to stop taking your current medications, but you must be on a stable dose of any psychotropic medications for at least four weeks before starting the trial.

Will I have to stop taking my current medications?

Participants must be on a stable dose of their current psychotropic medications for at least four weeks before starting the study. If you have recently started any new medications, you may need to wait until they are stable for four weeks before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using oxytocin as a nasal spray is generally safe and well-tolerated. Studies have found it has a strong safety record, with people typically not experiencing serious side effects. Oxytocin is also affordable and accessible, making it a promising treatment option. Although not all studies demonstrate its effectiveness in reducing PTSD symptoms, its safety makes it worth considering for those exploring new treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for PTSD, which often include antidepressants like SSRIs or trauma-focused therapies, oxytocin offers a unique approach by harnessing a naturally occurring hormone known for its role in social bonding and stress reduction. Researchers are excited about oxytocin because it is administered intranasally, allowing for rapid absorption and potentially quicker effects. This method could enhance emotional regulation and social functioning, offering a novel pathway to alleviate PTSD symptoms that current treatments might not address as effectively.

What evidence suggests that oxytocin might be an effective treatment for PTSD?

This trial will compare the effects of oxytocin and a placebo in treating PTSD. Research suggests that oxytocin might enhance the effectiveness of PTSD treatments, especially when combined with proven therapy methods. Oxytocin seems to aid by influencing brain areas that manage emotions and stress. Some studies have shown that oxytocin can lessen PTSD symptoms, although evidence from single doses remains limited. In animal studies, oxytocin reduced reactions to trauma. Overall, oxytocin shows promise as a way to support existing PTSD therapies and improve outcomes for those affected. ^{1 2 3 4 5}

Who Is on the Research Team?

Julianne Christina Flanagan, PhD

Principal Investigator

Ralph H. Johnson VA Medical Center, Charleston, SC

Are You a Good Fit for This Trial?

This trial is for Veterans with PTSD, who can consent and perform well on a mental status exam. They may have mood or anxiety disorders but not bipolar disorder or current severe suicidal thoughts. Stable psychotropic medication use is okay.

Inclusion Criteria

I have been on a stable dose of my mental health medication for at least 4 weeks.

You may have a mood disorder, except for bipolar affective disorder.

The study is only open to military veterans.

Exclusion Criteria

I started taking medication for anxiety, depression, or mood stabilization in the last 4 weeks.

Pregnancy or breastfeeding for women

Participants who present a serious suicide risk or are likely to require hospitalization during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Prolonged Exposure (PE) therapy combined with either oxytocin or placebo for PTSD

10 weeks

Sessions may be completed via home-based telemedicine

Follow-up

Participants are monitored for PTSD symptom severity and treatment adherence

6 months

Follow-up assessments at 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Oxytocin
• Placebo

Trial Overview

The study tests if oxytocin can improve PTSD symptoms and treatment retention in Veterans undergoing Prolonged Exposure therapy, compared to a placebo. Participants can join sessions via telemedicine using VA approved apps.

How Is the Trial Designed?

Group I: Oxytocin Experimental Treatment 1 Intervention

40 IU intranasal oxytocin

Group II: Placebo Placebo Group 1 Intervention

intranasal saline spray

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

San Francisco VA Health Care System

Collaborator

Trials

11

Recruited

865,000+

Published Research Related to This Trial

Palonosetron is a highly effective 5-HT(3) receptor antagonist for preventing chemotherapy-induced nausea and vomiting, with 71.9% of the drug remaining unchanged in plasma for up to 96 hours after administration.

The drug is primarily eliminated through the kidneys, with 83% of the dose recovered in urine, and it was generally well tolerated by participants, with no significant cardiac effects observed during monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Stoltz, R., Parisi, S., Shah, A., et al.[2022]

The combination of netupitant and palonosetron is effective in preventing both acute and delayed nausea and vomiting caused by moderately and highly emetogenic chemotherapy, as supported by phase II and III clinical trials.

This treatment offers a convenient single-capsule dosage and has a favorable side effect profile, although its high cost and administration logistics may pose challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of netupitant and palonosetron in chemotherapy-induced nausea and vomiting. Abramovitz, RB., Gaertner, KM.[2018]

Palonosetron, a new 5-HT3 receptor antagonist, has been shown to effectively prevent both acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately to highly emetogenic chemotherapy, demonstrating a longer half-life and higher binding affinity than older agents.

In clinical trials, palonosetron was as effective in controlling CINV during subsequent chemotherapy cycles as it was during the initial treatment, with no significant differences in safety profiles compared to other 5-HT3 receptor antagonists like ondansetron and dolasetron.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Navari, RM.[2018]

Oxytocin (OXT) shows potential to enhance psychotherapeutic treatments for PTSD by reducing stress responses and aiding recovery, which could lead to improved treatment outcomes for patients.

OXT may help counteract memory impairments caused by stress and promote social support seeking, both of which are important for resilience and effective therapy in PTSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication-Enhanced Psychotherapy for Posttraumatic Stress Disorder: Recent Findings on Oxytocin's Involvement in the Neurobiology and Treatment of Posttraumatic Stress Disorder. Preckel, K., Trautmann, S., Kanske, P.[2022]

In a study involving 384 patients at risk for postoperative nausea and vomiting (PONV), a single intravenous dose of 0.075 mg palonosetron significantly improved the complete response rates at 24 and 72 hours compared to a placebo, with rates of 68.1% and 65.3% respectively.

The incidence of nausea and vomiting was also lower in the palonosetron group at 2, 24, and 72 hours post-treatment, while the safety profile was comparable to the placebo, indicating that palonosetron is an effective and safe option for managing PONV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized, double-blind, multicenter trial to evaluate the therapeutic efficacy and safety of palonosetron in the treatment of postoperative nausea and vomiting over a 72-h period. Hahm, TS., Hwang, JW., Kim, WH., et al.[2021]

Oxytocin may enhance the effectiveness of cognitive-behavioral therapy (CBT) for posttraumatic stress disorder (PTSD) by promoting a sense of safety, which is crucial for successful treatment.

The proposed mechanisms for oxytocin's effectiveness include reducing fear responses by decreasing amygdala activation and enhancing social interactions, both of which are important for patients with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder. Olff, M., Langeland, W., Witteveen, A., et al.[2019]

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 pilot study involving 17 participants with PTSD explored the combination of intranasal oxytocin and Prolonged Exposure (PE) therapy, showing that oxytocin may help reduce PTSD and depression symptoms and improve the therapeutic alliance, although these results were not statistically significant.

The study demonstrated the feasibility and safety of using oxytocin with PE therapy, suggesting that larger studies are needed to confirm its effectiveness and understand how it might enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. Flanagan, JC., Sippel, LM., Wahlquist, A., et al.[2019]

Oxytocin has been studied for its potential to alleviate symptoms of PTSD, showing some positive effects according to research by Koch et al.

However, the effects observed were small, raising questions about the clinical significance and overall effectiveness of oxytocin as a treatment for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxytocin for the treatment of PTSD?] Dumont, GJH.[2021]

In a phase II study involving 58 patients receiving moderately emetogenic chemotherapy, the combination of palonosetron, dexamethasone, and aprepitant resulted in an 88% complete response rate in preventing nausea and vomiting during the first 24 hours after treatment.

The treatment was well tolerated with no unexpected adverse events, demonstrating that this combination therapy is both safe and highly effective for managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. Grote, T., Hajdenberg, J., Cartmell, A., et al.[2018]

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]

In a study using a rat model of PTSD, systemic administration of oxytocin (OXT) was found to impair the extinction of fear memories, suggesting that it may not be effective for treating PTSD as previously thought.

While OXT delayed fear extinction in non-stressed (sham) rats, it had no significant effect on the impaired fear extinction observed in stressed (SPS) rats, indicating that OXT's role in PTSD treatment may require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of systemic administration of oxytocin on contextual fear extinction in a rat model of post-traumatic stress disorder. Eskandarian, S., Vafaei, AA., Vaezi, GH., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6874414/

Augmenting Treatment for Posttraumatic Stress Disorder ...

Oxytocin holds promise for facilitating more effective PTSD treatment, particularly when used in combination with evidence-supported psychotherapy interventions ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04228289

Study Details | NCT04228289 | Oxytocin to Treat PTSD

Total PCL-5 Scores range from 17-85. Higher scores indicate greater symptom severity. End of Treatment (10 weeks). Secondary Outcome Measures ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S030645302030024X

Intranasal oxytocin as a potential therapeutic strategy in ...

IN-OT modulates activity in cognitive, emotion and reward brain areas in PTSD. · Clinical evidences of efficacy for single IN-OT administrations are limited.

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nature.com

nature.com/articles/s41398-020-0714-0

Emotional remodeling with oxytocin durably rescues ...

Our results show that three weeks following emotional remodeling with oxytocin, 83% of the rats identified as vulnerable to trauma became ...

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28087128/

Intranasal Oxytocin to Prevent Posttraumatic Stress ...

These findings suggest that oxytocin administration is a promising preventive intervention for PTSD for individuals with high acute PTSD symptoms.