NCT04104022

Prolonged Exposure Therapy for PTSD and Opioid Use Disorder

Completed NA Results posted Last updated 9 January 2025

What this trial tests

NA trial testing Prolonged Exposure Therapy in Post Traumatic Stress Disorder in 52 participants. Completed in 31 July 2023.

Timeline

6 April 2021

Primary endpoint
31 July 2023

31 July 2023

Quick facts

Lead sponsor	University of Vermont
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	52
Start date	6 April 2021
Primary completion	31 July 2023
Estimated completion	31 July 2023
Sites	1 location across United States

Drugs / interventions tested

• Prolonged Exposure Therapy
• Attendance-based monetary incentives

Conditions studied

• Post Traumatic Stress Disorder — all drugs for Post Traumatic Stress Disorder →
• Opioid-use Disorder — all drugs for Opioid-use Disorder →

Sponsor

University of Vermont

Who can join

18 and older, any sex, with Post Traumatic Stress Disorder or Opioid-use Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Posttraumatic Stress Disorder (PTSD) Symptom Severity Primary · 12 weeks

Change in PTSD symptom severity will be measured by the total symptom severity score of the Clinician Administered PTSD Scale for DSM-V (CAPS-5). The CAPS-5 is a clinician-administered clinical interview that produces a total symptom severity score that is obtained by summing the scores for each of the 20 items. Scores range from 0-80 with lower scores indicating less severe symptoms of PTSD. A negative sign in front of a number represents a decrease in score and less severe PTSD symptoms at 12 weeks compared to baseline. A greater decrease in score represents greater reduction in symptoms (mo

Group	Value	95% CI
OAT as Usual	-11.4	± 2.7
OAT+PET	-12.8	± 3.1
OAT+PET+	-18.3	± 2.6

Posttraumatic Stress Disorder (PTSD) Symptom Severity Secondary · 12 weeks

Mean PTSD symptom severity will be measured by the PTSD Checklist for DSM-V (PCL-5) total score. The PCL-5 is a self-report measure that produces a total score that is obtained by summing the scores for each of the the 20 items. Scores range from 0-80 with higher scores indicating more severe symptoms of PTSD.

Group	Value	95% CI
OAT as Usual	31.8	± 3.7
OAT+PET	28.9	± 4.4
OAT+PET+	21.7	± 3.5

Anxiety Symptom Severity Secondary · 12 weeks

Mean anxiety symptom severity will be measured by the Beck Anxiety Inventory (BAI) total score. The BAI is a self-report measure that produces a total score that is obtained by summing the scores for each of the 21 items. Scores range from 0-63 with higher scores indicating more severe symptoms of anxiety.

Group	Value	95% CI
OAT as Usual	18.1	± 2.6
OAT+PET	15.2	± 3.0
OAT+PET+	13.9	± 2.5

Depression Symptom Severity Secondary · 12 weeks

Mean depression symptom severity will be measured by the Beck Depression Inventory (BDI-II) total score. The BDI-II is a self-report measure that produces a total score that is obtained by summing the scores for each of the 21 items. Scores range from 0-63 with higher scores indicating more severe symptoms of depression.

Group	Value	95% CI
OAT as Usual	22.4	± 3.0
OAT+PET	23.1	± 3.3
OAT+PET+	18.6	± 2.8

Number of Participants Achieving Illicit Opioid Abstinence Secondary · 12 weeks

Illicit opioid abstinence will be measured by the overall percentage of urinalyses biochemically verified to be abstinent for illicit opioids at the end of the intervention period.

Group	Value	95% CI
OAT as Usual	13
OAT+PET	8
OAT+PET+	14

Psychiatric Problems Related to Substance Use Secondary · 12 weeks

Psychiatric problems related to substance use will be measured by the Addiction Severity Index (ASI) Psychiatric subscale score. The ASI is a clinician-administered structured interview. Scores for this subscale range from 0-1 with higher scores indicating more severe psychiatric consequences of substance use.

Group	Value	95% CI
OAT as Usual	0.39	± 0.04
OAT+PET	0.37	± 0.05
OAT+PET+	0.33	± 0.04

Number of Participants Who Report Abstinence From Illicit Non-opioid Substance Use Secondary · 12 weeks

Abstinence from illicit non-opioid substance use will be measured by the Timeline Follow-back (TLFB). The TLFB will be administered by an interviewer and involves participants retrospectively estimating their illicit non-opioid substance use (e.g., amphetamines, benzodiazepines, cocaine) during the 30 days prior to the interview date. Abstinence from illicit non-opioid substance use will be measured by the overall number of participants reporting abstinence from illicit non-opioid substances .

Group	Value	95% CI
OAT as Usual	11
OAT+PET	8
OAT+PET+	13

Pain Intensity and Interference Secondary · 12 weeks

For participants who endorsed the presence of pain during the past month, pain intensity and interference will be measured by Brief Pain Inventory -Short Form (BPI-SF). The BPI-SF is a self-report measure of pain intensity and interference in function during the past week. The pain intensity section of the BPI includes a rating of average pain intensity; whereas, the functional interference section consists of a rating of pain interference on general activity. Items assessing pain intensity and functional interference are scored from 0-10 with higher scores indicating greater pain severity and

Pain intensity

Group	Value	95% CI
OAT as Usual	4.9	± 2.6
OAT+PET	5.0	± 2.0
OAT+PET+	4.0	± 2.4

Pain interference

Group	Value	95% CI
OAT as Usual	6.0	± 3.6
OAT+PET	5.0	± 4.4
OAT+PET+	5.8	± 2.2

Delay Discounting Secondary · 12 weeks

Rates of delay discounting will be measured by the Monetary Choice Questionnaire (MCQ). The MCQ is a 27-item self-report measure consisting of items that presents a choice between smaller, immediate and larger, delayed monetary rewards. Immediate reward values ranged from $11 to $80, delayed rewards ranged from $25 to $85 and the length of the delay ranged from 7 days to 186 days. "Discounting rates," or k-values, are calculated from individuals' choices across items and represent rates at which the individual devalues rewards overall. The estimate of participant's discounting "k" was estimate

Group	Value	95% CI
OAT as Usual	0.05	± 0.02
OAT+PET	0.02	± 0.01
OAT+PET+	0.03	± 0.01

Insomnia Severity Secondary · 12 weeks

Insomnia severity will be measured by the Insomnia Severity Index (ISI). The ISI is a self-report measure that consists of 7 items that are scored from 0-4. The ISI produces a total score that is obtained by summing the scores for each of the the 7 items. Scores range from 0-28 with higher scores indicating more severe symptoms of insomnia.

Group	Value	95% CI
OAT as Usual	15.0	± 1.6
OAT+PET	14.7	± 1.9
OAT+PET+	13.0	± 1.6

Adverse events — posted to ClinicalTrials.gov

Time frame: 12 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

OAT as Usual

Serious: 0/17 (0%)

Deaths: 0/17

OAT+PET

Serious: 0/17 (0%)

Deaths: 0/17

OAT+PET+

Serious: 0/18 (0%)

Deaths: 0/18

Other adverse events (1 terms — click to expand)

Reaction	System	OAT as Usual	OAT+PET	OAT+PET+
Adverse events not categorized by organ system	General disorders	—	—	—

Data from ClinicalTrials.gov NCT04104022 adverse events section.

Sponsor's own 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 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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. A novel prolonged exposure therapy protocol for improving therapy session attendance and PTSD symptoms among adults receiving buprenorphine or methadone treatment.
   Peck KR, Giannini J, Badger GJ, Cole R, et al · · 2025 · cited 2× · PMID 39642783 · DOI 10.1016/j.drugalcdep.2024.112507
2. The Impact of Prolonged Exposure Therapy on Posttraumatic Stress Disorder Symptom Clusters in Adults Maintained on Medications for Opioid Use Disorder.
   Giannini JA, Badger GJ, Cole R, Peck KR. · · 2025 · cited 1× · PMID 41362052 · DOI 10.1002/cpp.70199