PTSDPhase 2NCT04228289
Oxytocin to Treat PTSD
A Phase 2 study testing Oxytocin in people with PTSD, run by VA Office of Research and Development at 2 sites in United States.
Trial summary
Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition that disproportionately affects Veterans. Prolonged Exposure (PE) therapy is a "gold standard" treatment for PTSD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PTSD
- What is being tested?
- Oxytocin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2021to 31 Aug 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Veteran
- Any race or ethnicity
- Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of the assessment instruments (> 26 on the Mini Mental Status Exam)
- Meet DSM-5 diagnostic criteria for current (i.e., past 6 months) PTSD (assessed via the CAPS-5)
- participants may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria)
- anxiety disorders (e.g. panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder)
- Participants taking psychotropic medications will be required to be maintained on a stable dose for at least four weeks before study initiation
Who cannot join
- Meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, or with current suicidal or homicidal ideation and intent
- those participants will be referred clinically
- Participants who present a serious suicide risk or are likely to require hospitalization during the study
- Participants on maintenance anxiolytic, antidepressant, or mood stabilizing medications, which have been initiated during the past 4 weeks
- Pregnancy or breastfeeding for women
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, 29401-5703
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121
About this study
Official title: Enhancing Prolonged Exposure Therapy for PTSD With Oxytocin
Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition that disproportionately affects Veterans. Prolonged Exposure (PE) therapy is a "gold standard" treatment for PTSD. However, approximately one-third of Veterans fail to receive an adequate dose of treatment because they prematurely drop out of PE therapy. There is also room to improve PE treatment outcomes. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, the proposed randomized clinical trial will examine the ability of oxytocin (as compared with placebo) combined with PE to reduce PTSD symptom severity, improve the rate of PTSD symptom reduction, and to enhance PE treatment retention and adherence. This two-site study will leverage the investments made in the nationwide rollout off PE therapy and has the potential to significantly improve mental health care among Veterans, advance the science in this area, and identify mechanisms underlying positive PTSD treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office
Read the detailed description
Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. PTSD is a chronic disorder that is associated with significant morbidity, mortality, disability, and costly health care expenditures. The clinical impairment associated with PTSD among Veterans is severe and associated with comorbid depression, suicidality, substance abuse, physical health problems, interpersonal violence, and neuropsychiatric impairment. Despite these pervasive health consequences, the current treatment services offered to Veterans do not adequately address PTSD. Several promising psychosocial interventions, including Prolonged Exposure (PE) therapy, have been developed for the treatment of PTSD. Although PE is one of the most widely used evidence-based treatments for PTSD, there is substantial room for improvement in outcomes and retention rates. For example, approximately one-third of patients dropout of PE treatment prematurely, and the highest dropout rates occur among Veterans. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, identifying pharmacotherapies to enhance PTSD treatment retention and outcomes is critical. Accumulating data from the investigators' group and others suggests that oxytocin is a promising candidate to achieve this goal. Oxytocin is known to promote prosocial behaviors associated with successful psychosocial treatment outcomes (e.g., trust, safety, social cognition) and has demonstrated positive effects on extinction learning in animal and human stress models. Furthermore, recent neuroimaging studies show that oxytocin has the ability to ameliorate dysregulation of the corticolimbic brain circuitry, which is a central component of the pathophysiology and maintenance of PTSD. In the only study to date examining the feasibility, acceptability, and preliminary efficacy of augmenting PE with oxytocin, the investigators' group found that participants randomized to the oxytocin condition demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores compared to participants randomized to the placebo condition. Therefore, the primary objective of the proposed two-site Phase II study is to examine the ability of oxytocin (vs. placebo) combined with PE therapy to (1) reduce PTSD symptom severity, (2) improve rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, the investigators will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6 month follow-up). The proposed study directly addresses the mission of the Veterans Health Administration Blueprint for Excellence in that it seeks to advance personalized and proactive mental health care opportunities for Veterans. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the neurobiological mechanisms underlying PTSD and positive treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxytocinDrug
Also called Pitocin
40 IU intranasal spray
PlaceboOther
Also called Saline
matching intranasal spray
| Study group | Role | What they receive |
|---|---|---|
| Oxytocin | Experimental | 40 IU intranasal oxytocin Receives: Drug: Oxytocin |
| Placebo | Placebo comparator | intranasal saline spray Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated
Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered Post Traumatic Stress Disorder (PTSD) Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms.
The CAPS-5 is a 30-item structured interview. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 PTSD symptoms, each with severity scores ranging from 0-4. The overall total severity score for CAPS-5 ranges from 0-80, with lower scores representing better outcomes (less severe PTSD).
Measured: From baseline to of Treatment (10 weeks)
Change in Post Traumatic Stress Disorder Symptom Severity - Self Report
Change in Post Traumatic Stress Disorder (PTSD) symptom severity as measured by the Posttraumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5](PCL-5) for self-reported symptoms.
The PCL-5 is a 20-item self-report measure that assesses the 20 symptoms of PTSD. The rating scale is 0-4 for each symptom/item, and overall scores range from 0-80, with lower scores representing better outcomes (less severe PTSD).
Measured: From baseline to end of Treatment (10 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start1 Jan 2021
- Primary completion28 Feb 2025
- Study completion31 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 1:1 manner to one of two drug conditions
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- San Francisco VA Health Care System
- Responsible party
- Sponsor
- Investigators
- Julianne Christina Flanagan, PhD, Principal investigator, Ralph H. Johnson VA Medical Center, Charleston, SC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04228289
- Sponsor's protocol ID
- MHBB-001-19S
- Status last verified
- Feb 2026
- First submitted
- 30 Dec 2019
- Last updated
- 11 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Flanagan JC, Mitchell JM, Baker NL, Woolley J, Wangelin B, Back SE, McQuaid JR, Neylan TC, Wolfe WR, Brady KT. Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. Contemp Clin Trials. 2020 Aug;95:106074. doi: 10.1016/j.cct.2020.106074. Epub 2020 Jun 16.
PubMed 32561468
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing Prolonged Exposure Therapy for PTSD With Oxytocin
- ClinicalTrials.gov ID
- NCT04228289
- Acronym / sponsor ID
- MHBB-001-19S
- Conditions
- PTSD
- Keywords
- PTSD, Veterans, Oxytocin, Mental Health, Psychophysiology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- San Francisco VA Health Care System
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 31 Aug 2025 (actual)
- First posted
- 14 Jan 2020 (actual)
- Results
- Posted 11 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition that disproportionately affects Veterans. Prolonged Exposure (PE) therapy is a "gold standard" treatment for PTSD. However, approximately one-third of Veterans fail to receive an adequate dose of treatment because they prematurely drop out of PE therapy. There is also room to improve PE treatment outcomes. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, the proposed randomized clinical trial will examine the ability of oxytocin (as compared with placebo) combined with PE to reduce PTSD symptom severity, improve the rate of PTSD symptom reduction, and to enhance PE treatment retention and adherence. This two-site study will leverage the investments made in the nationwide rollout off PE therapy and has the potential to significantly improve mental health care among Veterans, advance the science in this area, and identify mechanisms underlying positive PTSD treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office
Detailed description
Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. PTSD is a chronic disorder that is associated with significant morbidity, mortality, disability, and costly health care expenditures. The clinical impairment associated with PTSD among Veterans is severe and associated with comorbid depression, suicidality, substance abuse, physical health problems, interpersonal violence, and neuropsychiatric impairment. Despite these pervasive health consequences, the current treatment services offered to Veterans do not adequately address PTSD. Several promising psychosocial interventions, including Prolonged Exposure (PE) therapy, have been developed for the treatment of PTSD. Although PE is one of the most widely used evidence-based treatments for PTSD, there is substantial room for improvement in outcomes and retention rates. For example, approximately one-third of patients dropout of PE treatment prematurely, and the highest dropout rates occur among Veterans. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, identifying pharmacotherapies to enhance PTSD treatment retention and outcomes is critical. Accumulating data from the investigators' group and others suggests that oxytocin is a promising candidate to achieve this goal. Oxytocin is known to promote prosocial behaviors associated with successful psychosocial treatment outcomes (e.g., trust, safety, social cognition) and has demonstrated positive effects on extinction learning in animal and human stress models. Furthermore, recent neuroimaging studies show that oxytocin has the ability to ameliorate dysregulation of the corticolimbic brain circuitry, which is a central component of the pathophysiology and maintenance of PTSD. In the only study to date examining the feasibility, acceptability, and preliminary efficacy of augmenting PE with oxytocin, the investigators' group found that participants randomized to the oxytocin condition demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores compared to participants randomized to the placebo condition. Therefore, the primary objective of the proposed two-site Phase II study is to examine the ability of oxytocin (vs. placebo) combined with PE therapy to (1) reduce PTSD symptom severity, (2) improve rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, the investigators will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6 month follow-up). The proposed study directly addresses the mission of the Veterans Health Administration Blueprint for Excellence in that it seeks to advance personalized and proactive mental health care opportunities for Veterans. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the neurobiological mechanisms underlying PTSD and positive treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized in a 1:1 manner to one of two drug conditions
| Arm | Type | Receives |
|---|---|---|
| Oxytocin | Experimental | Drug: Oxytocin40 IU intranasal oxytocin |
| Placebo | Placebo comparator | Other: Placebointranasal saline spray |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Veteran
- Any race or ethnicity
- Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of the assessment instruments (> 26 on the Mini Mental Status Exam)
- Meet DSM-5 diagnostic criteria for current (i.e., past 6 months) PTSD (assessed via the CAPS-5)
- Participants taking psychotropic medications will be required to be maintained on a stable dose for at least four weeks before study initiation
Key exclusion criteria (5 listed)
- Meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, or with current suicidal or homicidal ideation and intent
- Participants who present a serious suicide risk or are likely to require hospitalization during the study
- Participants on maintenance anxiolytic, antidepressant, or mood stabilizing medications, which have been initiated during the past 4 weeks
- Pregnancy or breastfeeding for women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxytocinAlso: Pitocin40 IU intranasal spray | Drug | Oxytocin |
| PlaceboAlso: Salinematching intranasal spray | Other | Placebo |
Primary outcome
Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated
Time frame: From baseline to of Treatment (10 weeks)
Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered Post Traumatic Stress Disorder (PTSD) Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms. The CAPS-5 is a 30-item structured interview. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 PTSD symptoms, each with severity scores ranging from 0-4. The overall total severity score for CAPS-5 ranges from 0-80, with lower scores representing better outcomes (less severe PTSD).
Change in Post Traumatic Stress Disorder Symptom Severity - Self Report
Time frame: From baseline to end of Treatment (10 weeks)
Change in Post Traumatic Stress Disorder (PTSD) symptom severity as measured by the Posttraumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5](PCL-5) for self-reported symptoms. The PCL-5 is a 20-item self-report measure that assesses the 20 symptoms of PTSD. The rating scale is 0-4 for each symptom/item, and overall scores range from 0-80, with lower scores representing better outcomes (less severe PTSD).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32561468Flanagan JC, Mitchell JM, Baker NL, Woolley J, Wangelin B, Back SE, McQuaid JR, Neylan TC, Wolfe WR, Brady KT. Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. Contemp Clin Trials. 2020 Aug;95:106074. doi: 10.1016/j.cct.2020.106074. Epub 2020 Jun 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julianne Christina Flanagan, PhD principal investigator
Ralph H. Johnson VA Medical Center, Charleston, SC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxytocin in people with PTSD, run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated (time frame: From baseline to of Treatment (10 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04228289, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.