PTSDPhase 2COPE+OTNCT04523922
Oxytocin to Enhance Integrated Treatment for AUD and PTSD
A Phase 2 study testing 40 IU Intranasal Oxytocin and Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure in people with PTSD and Alcohol Use Disorder, run by Medical University of South Carolina at 1 site in United States.
Trial summary
The primary objective of the proposed Stage II study is to examine the efficacy of oxytocin (OT) as compared to placebo in reducing (1) alcohol use disorder (AUD) symptoms, and (2) post-traumatic stress disorder (PTSD) symptoms among Veterans receiving COPE therapy (Concurrent Treatment of PTSD and Substance Use… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- PTSD, Alcohol Use Disorder
- What is being tested?
- 40 IU Intranasal Oxytocin and Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 175 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2021to 13 Apr 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female; U.S. military Veteran, any race or ethnicity; aged 18-70 years.
- Able to provide written informed consent.
- Meet DSM-5 diagnostic criteria for current moderate to severe alcohol use disorder.
- Meet DSM-5 diagnostic criteria for current PTSD as assessed by the CAPS-5.
- Participants may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or anxiety disorders. Concurrent substance use disorders (e.g., marijuana) are acceptable provided alcohol is the participant's primary substance of choice.
- Participants taking psychotropic medications will be required to be maintained on a stable dose for at least 4 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 for services.
- Participants on psychotropic medications which have been initiated during the past 4 weeks.
- Acute alcohol withdrawal as indicated by CIWA-Ar scores >8.
- Pregnancy or breastfeeding for women.
- For MRI scan component: history of seizures or severe head injury, implanted metal devices or other metal (e.g., shrapnel). These participants will be eligible to enroll in the clinical trial but will not be eligible to participate in the neuroimaging component of the study.
- Currently enrolled in behavioral treatment for AUD or PTSD.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29401
About this study
Official title: Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD
The primary objective of the proposed Stage II study is to examine the efficacy of oxytocin (OT) as compared to placebo in reducing (1) alcohol use disorder (AUD) symptoms, and (2) post-traumatic stress disorder (PTSD) symptoms among Veterans receiving COPE therapy (Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure). To evaluate purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre- and post-treatment.
Read the detailed description
Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with significant morbidity, mortality, and health care expenditures. Military Veterans are at increased risk for co-occurring AUD and PTSD, with prevalence rates 2-4 times higher than the general population. Our group developed an integrated intervention entitled Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE). COPE incorporates empirically validated cognitive-behavioral techniques for AUD with Prolonged Exposure (PE) therapy for PTSD. Several randomized controlled trials among Veterans and civilians demonstrate efficacy of COPE in significantly reducing AUD and PTSD symptoms. Despite the positive findings, there remains substantial room for improving treatment outcomes and enhancing retention. Accumulating data suggest that the neuropeptide oxytocin (OT) is a promising candidate to enhance psychosocial interventions for co-occurring AUD and PTSD, as OT targets neurobiological and behavioral dysregulation common to both disorders. Preclinical and clinical studies demonstrate the ability of OT to ameliorate a variety of alcohol-related behaviors (e.g., craving, withdrawal symptoms, tolerance, ethanol self-administration), enhance fear extinction, and promote prosocial behaviors associated with successful psychosocial treatment outcomes. In a randomized controlled pilot study, our group found that OT administration prior to weekly Prolonged Exposure (PE) therapy sessions was safe, well-tolerated, and resulted in accelerated reduction in PTSD symptoms as compared to placebo. Although the empirical and theoretical support for augmenting psychosocial interventions such as COPE with OT is robust, no studies to date have examined this combined approach. The primary objective of the proposed Stage II study is to examine the efficacy of OT as compared to placebo in reducing (1) AUD symptoms, and (2) PTSD symptoms among Veterans (50% women) receiving COPE therapy. To accomplish this, we will employ a manualized, evidence-based, cognitive-behavioral intervention (COPE); a randomized, double-blind, placebo-controlled study design; and standardized, repeated dependent measures of clinical outcomes at multiple time points. In addition, to investigate neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre-and post-treatment .
- Conditions
- PTSD, Alcohol Use Disorder
- Being tested
- 40 IU Intranasal Oxytocin, Placebo, Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure
- Medical subject headings
- Stress Disorders, Post-Traumatic, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
40 IU Intranasal OxytocinDrug
Also called oxytocin
40 IU Intranasal Oxytocin self administered 30 minutes prior to each COPE session.
PlaceboDrug
Also called saline
Placebo (intranasal saline spray) self administered 30 minutes prior to each COPE session.
Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged ExposureBehavioural
Also called COPE
12 weekly sessions of COPE therapy for PTSD and AUD.
| Study group | Role | What they receive |
|---|---|---|
| Oxytocin Treatment Group | Experimental | Participants will receive 12 weekly sessions of Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE Therapy), plus intranasal Oxytocin.
40-IU dose of Oxytocin self-administered 30 minutes prior to the start of each weekly COPE session. Receives: Drug: 40 IU Intranasal Oxytocin; Behavioral: Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure |
| Placebo Group | Active comparator | Participants will receive 12 weekly sessions of Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE Therapy), plus placebo (intranasal saline spray).
Intranasal dose of saline spray self-administered 30 minutes prior to the start of each weekly COPE session. Receives: Drug: Placebo; Behavioral: Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in alcohol use
Change in percent days abstinent and heavy drinking days as measured by the TimeLine Follow-Back (TLFB).
Measured: From baseline to week 12 and 3 and 6 month follow ups
Change in PTSD symptom severity - clinician rated
Change in clinician-rated PTSD symptom severity will be measured with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5).
Measured: From baseline to week 12 and 3 and 6 month follow ups
Change in PTSD symptom severity - self report
Change in self-reported PTSD symptom severity will be measured with the PTSD Checklist for DSM-5 (PCL-5).
Measured: From baseline to week 12 and 3 and 6 month follow ups
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2020
- Study start29 Mar 2021
- Primary completion13 Apr 2026
- Study completion13 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 Medical University of South CarolinaThe 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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Sudie Back, Medical University of South Carolina
- Investigators
- Sudie Back, PhD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04523922
- Sponsor's protocol ID
- Pro00103198
- Acronym
- COPE+OT
- Status last verified
- Jul 2026
- First submitted
- 19 Aug 2020
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Back SE, Flanagan JC, Killeen T, Saraiya TC, Brown DG, Jarnecke AM, Rothbaum AO, Joseph J, Ana ES, de Arellano A, Shoemaker HL, Dixon RA, Nietert PJ, Brady KT. COPE and oxytocin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in U.S. military veterans. Contemp Clin Trials. 2023 Mar;126:107084. doi: 10.1016/j.cct.2023.107084. Epub 2023 Jan 13.
PubMed 36646315
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD
- ClinicalTrials.gov ID
- NCT04523922
- Acronym / sponsor ID
- COPE+OT / Pro00103198
- Conditions
- PTSD, Alcohol Use Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 175 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- 13 Apr 2026 (actual)
- Study completion
- 13 Apr 2026 (actual)
- First posted
- 24 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the proposed Stage II study is to examine the efficacy of oxytocin (OT) as compared to placebo in reducing (1) alcohol use disorder (AUD) symptoms, and (2) post-traumatic stress disorder (PTSD) symptoms among Veterans receiving COPE therapy (Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure). To evaluate purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre- and post-treatment.
Detailed description
Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with significant morbidity, mortality, and health care expenditures. Military Veterans are at increased risk for co-occurring AUD and PTSD, with prevalence rates 2-4 times higher than the general population. Our group developed an integrated intervention entitled Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE). COPE incorporates empirically validated cognitive-behavioral techniques for AUD with Prolonged Exposure (PE) therapy for PTSD. Several randomized controlled trials among Veterans and civilians demonstrate efficacy of COPE in significantly reducing AUD and PTSD symptoms. Despite the positive findings, there remains substantial room for improving treatment outcomes and enhancing retention. Accumulating data suggest that the neuropeptide oxytocin (OT) is a promising candidate to enhance psychosocial interventions for co-occurring AUD and PTSD, as OT targets neurobiological and behavioral dysregulation common to both disorders. Preclinical and clinical studies demonstrate the ability of OT to ameliorate a variety of alcohol-related behaviors (e.g., craving, withdrawal symptoms, tolerance, ethanol self-administration), enhance fear extinction, and promote prosocial behaviors associated with successful psychosocial treatment outcomes. In a randomized controlled pilot study, our group found that OT administration prior to weekly Prolonged Exposure (PE) therapy sessions was safe, well-tolerated, and resulted in accelerated reduction in PTSD symptoms as compared to placebo. Although the empirical and theoretical support for augmenting psychosocial interventions such as COPE with OT is robust, no studies to date have examined this combined approach. The primary objective of the proposed Stage II study is to examine the efficacy of OT as compared to placebo in reducing (1) AUD symptoms, and (2) PTSD symptoms among Veterans (50% women) receiving COPE therapy. To accomplish this, we will employ a manualized, evidence-based, cognitive-behavioral intervention (COPE); a randomized, double-blind, placebo-controlled study design; and standardized, repeated dependent measures of clinical outcomes at multiple time points. In addition, to investigate neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre-and post-treatment .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oxytocin Treatment Group | Experimental | Drug: 40 IU Intranasal Oxytocin, Behavioral: Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged ExposureParticipants will receive 12 weekly sessions of Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE Therapy), plus intranasal Oxytocin. 40-IU dose of Oxytocin self-administered 30 minutes prior to the start of each weekly COPE session. |
| Placebo Group | Active comparator | Drug: Placebo, Behavioral: Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged ExposureParticipants will receive 12 weekly sessions of Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE Therapy), plus placebo (intranasal saline spray). Intranasal dose of saline spray self-administered 30 minutes prior to the start of each weekly COPE session. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female; U.S. military Veteran, any race or ethnicity; aged 18-70 years.
- Able to provide written informed consent.
- Meet DSM-5 diagnostic criteria for current moderate to severe alcohol use disorder.
- Meet DSM-5 diagnostic criteria for current PTSD as assessed by the CAPS-5.
- Participants may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or anxiety disorders. Concurrent substance use disorders (e.g., marijuana) are acceptable provided alcohol is the participant's primary substance of choice.
Key exclusion criteria (6 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. Those participants will be referred clinically for services.
- Participants on psychotropic medications which have been initiated during the past 4 weeks.
- Acute alcohol withdrawal as indicated by CIWA-Ar scores >8.
- Pregnancy or breastfeeding for women.
- For MRI scan component: history of seizures or severe head injury, implanted metal devices or other metal (e.g., shrapnel). These participants will be eligible to enroll in the clinical trial but will not be eligible to participate in the neuroimaging component of the study.
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 |
|---|---|---|
| 40 IU Intranasal OxytocinAlso: oxytocin40 IU Intranasal Oxytocin self administered 30 minutes prior to each COPE session. | Drug | Oxytocin Treatment Group |
| PlaceboAlso: salinePlacebo (intranasal saline spray) self administered 30 minutes prior to each COPE session. | Drug | Placebo Group |
| Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged ExposureAlso: COPE12 weekly sessions of COPE therapy for PTSD and AUD. | Behavioural | Oxytocin Treatment Group, Placebo Group |
Primary outcome
Change in alcohol use
Time frame: From baseline to week 12 and 3 and 6 month follow ups
Change in percent days abstinent and heavy drinking days as measured by the TimeLine Follow-Back (TLFB).
Change in PTSD symptom severity - clinician rated
Time frame: From baseline to week 12 and 3 and 6 month follow ups
Change in clinician-rated PTSD symptom severity will be measured with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5).
Change in PTSD symptom severity - self report
Time frame: From baseline to week 12 and 3 and 6 month follow ups
Change in self-reported PTSD symptom severity will be measured with the PTSD Checklist for DSM-5 (PCL-5).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Derived from this study: PubMed 36646315Back SE, Flanagan JC, Killeen T, Saraiya TC, Brown DG, Jarnecke AM, Rothbaum AO, Joseph J, Ana ES, de Arellano A, Shoemaker HL, Dixon RA, Nietert PJ, Brady KT. COPE and oxytocin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in U.S. military veterans. Contemp Clin Trials. 2023 Mar;126:107084. doi: 10.1016/j.cct.2023.107084. Epub 2023 Jan 13.
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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.
Sudie Back, PhD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 40 IU Intranasal Oxytocin and Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure in people with PTSD and Alcohol Use Disorder, run by Medical University of South Carolina at 1 site 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 6 inclusion and 6 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 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 alcohol use (time frame: From baseline to week 12 and 3 and 6 month follow ups). The study lists 3 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 NCT04523922, 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 27 Jul 2026.