Oxytocin to Enhance Integrated Treatment for AUD and PTSD

NCT ID: NCT04523922

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-29
• Study Completion Date: 2026-12-01

Brief 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 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 .

Conditions

PTSD; Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Oxytocin Treatment Group

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.

Group Type: EXPERIMENTAL

40 IU Intranasal Oxytocin

Intervention Type: DRUG

40 IU Intranasal Oxytocin self administered 30 minutes prior to each COPE session.

Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure

Intervention Type: BEHAVIORAL

12 weekly sessions of COPE therapy for PTSD and AUD.

Placebo Group

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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (intranasal saline spray) self administered 30 minutes prior to each COPE session.

Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure

Intervention Type: BEHAVIORAL

12 weekly sessions of COPE therapy for PTSD and AUD.

Interventions

40 IU Intranasal Oxytocin

40 IU Intranasal Oxytocin self administered 30 minutes prior to each COPE session.

Intervention Type: DRUG

Placebo

Placebo (intranasal saline spray) self administered 30 minutes prior to each COPE session.

Intervention Type: DRUG

Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure

12 weekly sessions of COPE therapy for PTSD and AUD.

Intervention Type: BEHAVIORAL

Other Intervention Names

oxytocin; saline; COPE

Eligibility Criteria

Inclusion Criteria

1. Male or female; U.S. military Veteran, any race or ethnicity; aged 18-70 years.

2. Able to provide written informed consent.

3. Meet DSM-5 diagnostic criteria for current moderate to severe alcohol use disorder.

4. Meet DSM-5 diagnostic criteria for current PTSD as assessed by the CAPS-5.

Exclusion Criteria

6. Participants taking psychotropic medications will be required to be maintained on a stable dose for at least 4 weeks before study initiation.

1. 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.

2. Participants on psychotropic medications which have been initiated during the past 4 weeks.

3. Acute alcohol withdrawal as indicated by CIWA-Ar scores >8.

4. Pregnancy or breastfeeding for women.

5. 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.

6. Currently enrolled in behavioral treatment for AUD or PTSD.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Sudie Back

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sudie Back, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Stacey Sellers, MS

Role: CONTACT

sellersst@musc.edu

843-792-5807

Sudie Back, PhD

Role: CONTACT

backs@musc.edu

Facility Contacts

Stacey Sellers, MS

Role: primary

sellersst@musc.edu

843-792-5807

References

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.

Reference Type: DERIVED

PMID: 36646315 (View on PubMed)

Other Identifiers

Pro00103198

Identifier Type: -

Identifier Source: org_study_id