Oxytocin to Enhance Integrated Treatment for AUD and PTSD

Alcohol Use Disorder Clinical Trial

— COPE+OT  

Official title:

Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04523922
• Other study ID #: Pro00103198
• Status: Recruiting
• Phase: Phase 2
• Start date: March 29, 2021
• Est. completion date: January 1, 2026

Study information

• Verified date: January 2024
• Source: Medical University of South Carolina
• Contact: Stacey Sellers, MS
• Phone: 843-792-5807
• Email: sellersst[@]musc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 Disorders using Prolonged Exposure). To evaluate purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre- and post-treatment.

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 .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: January 1, 2026
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

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.

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

Exclusion Criteria:

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• PTSD

Intervention

Drug:
• 40 IU Intranasal Oxytocin
40 IU Intranasal Oxytocin self administered 30 minutes prior to each COPE session.
• Placebo
Placebo (intranasal saline spray) self administered 30 minutes prior to each COPE session.

Behavioral:
• Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure
12 weekly sessions of COPE therapy for PTSD and AUD.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in alcohol use	Change in percent days abstinent and heavy drinking days as measured by the TimeLine Follow-Back (TLFB).	From baseline to week 12 and 3 and 6 month follow ups
Primary	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).	From baseline to week 12 and 3 and 6 month follow ups
Primary	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).	From baseline to week 12 and 3 and 6 month follow ups