Prolonged Exposure Therapy for PTSD and Opioid Use Disorder

NCT ID: NCT04104022

Last Updated: 2025-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-06
• Study Completion Date: 2023-07-31

Brief Summary

Among patients with opioid use disorder (OUD), 90% report lifetime trauma exposure and 33% meet criteria for posttraumatic stress disorder (PTSD). The co-occurrence of OUD and PTSD is associated with worse mental health and opioid agonist treatment (OAT) outcomes relative to either diagnosis alone. Prolonged exposure therapy (PET) is an efficacious cognitive-behavioral treatment for reducing PTSD severity. Although preliminary findings indicate that PET may reduce PTSD symptom severity among patients receiving treatment for concomitant OUD, it is unclear to what extent improvements were a function of PET versus the effects of OAT itself. Therefore, the question of whether OAT alone may attenuate PTSD symptoms in the absence of intensive cognitive-behavioral therapy remains unanswered.

In this 12-week trial, we aim to investigate the contribution of PET above and beyond OAT alone for reducing PTSD symptoms among adults with concurrent PTSD and OUD. Participants will be randomized to one of three conditions: (a) OAT as usual, (b) OAT + PET, or (c) OAT + Enhanced PET (OAT+PET+). Those randomized to OAT as usual will continue to receive standard buprenorphine or methadone treatment from their current treatment provider and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at intake and Study Weeks 4, 8, and 12. In addition to receiving OAT and completing monthly assessments, OAT+PET participants will receive PET consisting of 12 weekly, individual sessions with a trained therapist. Finally, OAT+PET+ participants will receive the procedures noted above for the OAT+PET group plus monetary incentives delivered contingent upon completion of PET sessions. Given the poor PET adherence rates reported among patients with substance use disorders, the use of incentives will ensure that we evaluate PET effects among patients who receive a sufficient dose of therapy. The proposed study design will permit us to disentangle the effects of PET from the effects of OAT alone while also including experimental conditions that reflect real-world practice. Taken together, this project will produce important new scientific and clinically-relevant information related to the mechanisms through which OAT and PET promote reductions in PTSD symptomatology in a highly vulnerable clinical population.

Detailed Description

Among patients with opioid use disorder (OUD), 90% report lifetime trauma exposure and 33% meet criteria for posttraumatic stress disorder (PTSD). The co-occurrence of OUD and PTSD is associated with more severe mental health symptoms and worse opioid agonist treatment (OAT) outcomes relative to either diagnosis alone. Prolonged exposure therapy (PET) is an efficacious manualized cognitive-behavioral treatment for reducing PTSD severity. Although preliminary findings indicate that PET may reduce PTSD symptom severity among patients receiving treatment for concomitant OUD, it is unclear to what extent observed improvements were a function of PET versus the psychopharmacological effects of OAT itself. Therefore, the question of whether OAT alone may attenuate PTSD symptomatology in the absence of intensive cognitive-behavioral therapy remains unanswered and is important given the prevalence and deleterious effects of PTSD among OAT patients, as well as the ever-present constraints on mental health resources in substance use treatment settings.

The present study will investigate the contribution of PET above and beyond OAT alone for reducing PTSD symptomatology among adults with concurrent PTSD and OUD. Eligible participants who complete the informed consent process will be randomized to one of three conditions: (a) OAT as usual, (b) OAT + PET, or (c) OAT + Enhanced PET (OAT+PET+). Those randomized to OAT as usual will continue to receive standard buprenorphine or methadone treatment from their current treatment provider and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at intake and Study Weeks 4, 8, and 12. Follow-up assessment visits will be conducted in-person at our clinic following all relevant COVID-19-related CDC guidelines and university safety protocols. However, study measures may also be administered remotely via phone or telemedicine to reduce the risk of COVID-19 transmission. In addition to receiving OAT and completing monthly assessments, OAT+PET participants will receive PET consisting of 12 weekly, individual sessions with a trained therapist. Therapy sessions will be conducted at our research clinic or remotely via telemedicine to reduce the risk of COVID-19 transmission. Finally, OAT+PET+ participants will receive the procedures noted above for the OAT+PET group plus monetary incentives delivered contingent upon completion of PET sessions. Given the poor PET adherence rates reported among patients with substance use disorder (SUDs), the use of incentives will ensure that we evaluate PET effects among patients who receive a sufficient dose of therapy.

For inclusion in the study, participants must meet the following criteria: (a) > 18 years of age, (b) currently maintained on a stable methadone or buprenorphine dose for the treatment of OUD for >1 month prior to the study, (c) endorse >1 lifetime traumatic event, and (c) meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) PTSD diagnostic criteria (American Psychiatric Association, 2013). Exclusion criteria include: (a) the presence of an acute psychotic disorder, bipolar disorder with an active manic episode (but not simply the presence of bipolar disorder), (b) imminent risk for suicide, (c) a medical condition that may interfere with consent or participation (e.g., organic brain syndrome, dementia, head injury, neuropathy, etc.), and (d) illiteracy in English.

Participants randomized to OAT as usual will continue to receive standard buprenorphine or methadone maintenance from their current treatment provider and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at Study Weeks 4, 8, and 12. Follow-up assessment visits will be conducted in-person at our clinic following all relevant COVID-19-related CDC guidelines and university safety protocols. However, study measures may also be administered remotely via phone or telemedicine to reduce the risk of COVID-19 transmission. In addition to receiving standard buprenorphine- or methadone-maintenance treatment as described above and completing monthly assessments, OAT+PET participants will also receive 12 individual sessions of PET. Therapy sessions will be conducted at our research clinic or remotely via telemedicine to reduce the risk of COVID-19 transmission. Beginning in Study Week 1, OAT+PET participants will complete weekly 60-minute PET sessions provided by a therapist trained in PET. Participants randomized to the OAT+PET+ condition will receive the procedures noted above for the OAT+PET group plus monetary incentives delivered contingent upon completion of PET sessions. Each consecutive attended session will increase the voucher amount so that each consecutively attended appointment is worth an incrementally higher dollar amount. To support completion of the full 12-week PET protocol, we will also incorporate additional strategically-placed bonuses into the reinforcement schedule with the goal of maximizing the percentage of subjects who complete the full 12-session protocol. First, to support consistent (vs. sporadic) attendance, participants will receive a bonus for every two consecutive sessions attended. Second, to support completion of the full PET protocol, participants will receive an additional bonus upon completion of Session 12.

Conditions

Post Traumatic Stress Disorder; Opioid-use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OAT as usual

Those randomized to OAT as usual will continue to receive standard buprenorphine or methadone treatment and complete assessments of PTSD symptom severity, psychosocial functioning and drug use at intake and Study Weeks 4, 8, and 12.

Group Type: NO_INTERVENTION

No interventions assigned to this group

OAT+PET

In addition to receiving OAT and completing monthly assessments, OAT+PET participants will receive 12 weekly PET sessions with a trained therapist.

Group Type: ACTIVE_COMPARATOR

Prolonged Exposure Therapy

Intervention Type: BEHAVIORAL

Within the general population, prolonged exposure therapy (PET) is a widely-used, empirically-supported and manualized therapy that is regarded as a first-line cognitive-behavioral treatment for posttraumatic stress disorder (PTSD). PET is designed to disrupt the cycle of anxiety and avoidance that characterizes PTSD via sustained imaginal and in-vivo exposure exercises that deliberately and systematically expose patients to painful memories and current, real-life trauma reminders that were previously avoided, yet not inherently harmful. Overall, PET has well-documented efficacy for reducing PTSD symptom severity in both civilian and veteran populations. PET is effective for reducing PTSD symptoms regardless of whether it is delivered remotely or face-to-face. Recent data also suggest that PET can improve PTSD symptoms without exacerbating substance use or craving among patients with substance use disorders when PET and substance use disorder treatment are delivered concurrently.

OAT+PET+

OAT+PET+ participants will receive the procedures for the OAT+PET group plus monetary incentives contingent upon completion of PET sessions

Group Type: EXPERIMENTAL

Prolonged Exposure Therapy

Intervention Type: BEHAVIORAL

Within the general population, prolonged exposure therapy (PET) is a widely-used, empirically-supported and manualized therapy that is regarded as a first-line cognitive-behavioral treatment for posttraumatic stress disorder (PTSD). PET is designed to disrupt the cycle of anxiety and avoidance that characterizes PTSD via sustained imaginal and in-vivo exposure exercises that deliberately and systematically expose patients to painful memories and current, real-life trauma reminders that were previously avoided, yet not inherently harmful. Overall, PET has well-documented efficacy for reducing PTSD symptom severity in both civilian and veteran populations. PET is effective for reducing PTSD symptoms regardless of whether it is delivered remotely or face-to-face. Recent data also suggest that PET can improve PTSD symptoms without exacerbating substance use or craving among patients with substance use disorders when PET and substance use disorder treatment are delivered concurrently.

Attendance-based monetary incentives

Intervention Type: BEHAVIORAL

Participants will earn vouchers that have monetary value for attending scheduled PET appointments. Each consecutive attended session will increase the voucher amount so that each consecutively attended appointment is worth an incrementally higher dollar amount. To support completion of the full 12-week PET protocol, we will also incorporate additional strategically-placed bonuses into the reinforcement schedule with the goal of maximizing the percentage of subjects who complete the full 12-session protocol. First, to support consistent (vs. sporadic) attendance, participants will receive a bonus for every two consecutive sessions attended. Second, to support completion of the full PET protocol, participants will receive an additional bonus upon completion of Session 12.

Interventions

Prolonged Exposure Therapy

Within the general population, prolonged exposure therapy (PET) is a widely-used, empirically-supported and manualized therapy that is regarded as a first-line cognitive-behavioral treatment for posttraumatic stress disorder (PTSD). PET is designed to disrupt the cycle of anxiety and avoidance that characterizes PTSD via sustained imaginal and in-vivo exposure exercises that deliberately and systematically expose patients to painful memories and current, real-life trauma reminders that were previously avoided, yet not inherently harmful. Overall, PET has well-documented efficacy for reducing PTSD symptom severity in both civilian and veteran populations. PET is effective for reducing PTSD symptoms regardless of whether it is delivered remotely or face-to-face. Recent data also suggest that PET can improve PTSD symptoms without exacerbating substance use or craving among patients with substance use disorders when PET and substance use disorder treatment are delivered concurrently.

Intervention Type: BEHAVIORAL

Attendance-based monetary incentives

Participants will earn vouchers that have monetary value for attending scheduled PET appointments. Each consecutive attended session will increase the voucher amount so that each consecutively attended appointment is worth an incrementally higher dollar amount. To support completion of the full 12-week PET protocol, we will also incorporate additional strategically-placed bonuses into the reinforcement schedule with the goal of maximizing the percentage of subjects who complete the full 12-session protocol. First, to support consistent (vs. sporadic) attendance, participants will receive a bonus for every two consecutive sessions attended. Second, to support completion of the full PET protocol, participants will receive an additional bonus upon completion of Session 12.

Intervention Type: BEHAVIORAL

Other Intervention Names

Contingency management

Eligibility Criteria

Inclusion Criteria

• >18 years old
• currently maintained on a stable methadone or buprenorphine dose for >1 month prior to the study
• endorse >1 lifetime traumatic event
• meet current DSM-V posttraumatic stress disorder criteria

Exclusion Criteria

• Presence of an acute psychotic disorder, bipolar disorder with an active manic episode
• imminent risk for suicide
• a medical condition that may interfere with consent or participation
• illiteracy in English

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

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

University of Vermont

OTHER

Sponsor Role: lead

Responsible Party

Kelly Peck

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kelly Peck, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Locations

University of Vemont

Burlington, Vermont, United States

Countries

United States

References

Peck KR, Giannini J, Badger GJ, Cole R, Sigmon SC. A novel prolonged exposure therapy protocol for improving therapy session attendance and PTSD symptoms among adults receiving buprenorphine or methadone treatment. Drug Alcohol Depend. 2025 Jan 1;266:112507. doi: 10.1016/j.drugalcdep.2024.112507. Epub 2024 Nov 27.

Reference Type: DERIVED

PMID: 39642783 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P20GM103644

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHRBSS #STUDY00000318

Identifier Type: -

Identifier Source: org_study_id