- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04961190
A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD
October 31, 2022 updated by: University of Pennsylvania
A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD: What Works Best, and for Whom
Posttraumatic Stress Disorder (PTSD) remains a salient and debilitating problem, in the general population and for military veterans in particular.
Several psychological and pharmacological treatments for PTSD have evidence to support their efficacy.
However, the lack of comparative effectiveness data for PTSD treatments remains a major gap in the literature, which limits conclusions that can be drawn about which of these treatments work best.
The current study will compare the effectiveness of PTSD treatments with the strongest evidentiary support - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine - as well as the combination of these two treatments.
A randomized trial will be conducted with a large, diverse sample of veterans with PTSD (N = 450) recruited from 6 VA Medical Centers throughout the US.
Participants will complete baseline assessments, followed by an active treatment phase (involving up to 14 sessions of PE and/or medication management) with mid (7 week) and posttreatment (14 week) assessments, and follow-up assessments at 27 and 40 weeks.
Study outcomes will include PTSD severity, depression, quality of life and functioning, assessed via clinical ratings and self-report measures.
Further, a range of demographic and clinically relevant variables (e.g., trauma type/number, resilience) will be collected at baseline and examined as potential predictors or moderators of treatment response, addressing another gap in the PTSD treatment literature.
These data will be used to develop algorithms from predicting the optimal treatment for individual patients (i.e., "personalized advantage indices"; PAIs).
Effectiveness of the treatments will be compared using multilevel modeling.
PAIs will be developed by conducting bootstrapped analyses to select variables that predict or moderate outcomes (clinician rated PTSD severity at Week 14), followed by jacknife analyses to determine the magnitude of the predicted difference (representing an individual's "predicted advantage" of one treatment over the others).
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
Posttraumatic Stress Disorder (PTSD) remains a salient and debilitating problem, in the general population and for military veterans in particular.
Several psychological and pharmacological treatments for PTSD have evidence to support their efficacy.
However, the lack of comparative effectiveness trials for PTSD treatments remains a major gap in the literature, which limits conclusions that can be drawn about which of these treatments work best.
In particular, trials directly comparing efficacious psychotherapies and pharmacotherapies are needed to inform clinical decision making for patients and providers.
To address this gap, the proposed study will aim to compare the effectiveness of PTSD treatments with the strongest evidentiary support - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine - as well as the combination of these two treatments.
A randomized trial in proposed with a large, diverse sample of veterans with PTSD (N = 450) recruited from 6 Veterans Affairs Medical Centers throughout the US (in Philadelphia, Coatesville, Milwaukee, Dallas, San Diego, and Palo Alto).
Treatments conditions will reflect "real world" practice in these settings, and minimal exclusion criteria related to safety will be adopted, to maximize external validity.
Participants will be permitted to complete treatment sessions in person or via telehealth (based on evidence for equivalent outcomes across these modalities), to maximize patient access, recruitment, and generalizability.
Participants will complete baseline assessments, followed by 14 weeks of active treatment (involving up to 14 sessions of PE and/or medication management) with mid and posttreatment assessments after 7 and 14 weeks respectively, and then follow-up assessments at 27 and 40 weeks.
Primary outcomes will include PTSD severity, depression symptoms, quality of life and functioning, assessed via clinical ratings and self-report measures.
Further, a range of demographic and clinically relevant variables (e.g., trauma type/number, physiological arousal) will be collected at baseline and examined as potential predictors or moderators of treatment response, addressing another key gap in the PTSD treatment literature.
Specifically, these data will be used to develop algorithms from predicting the optimal treatment for individual patients (i.e., "personalized advantage indices"; PAIs), a statistical approach which has advanced the depression treatment literature but has only been used in a limited capacity in PTSD research.
The project will include an Advisory Board composed of clinician and patient representatives, in order to obtain stakeholder feedback at every stage of the study (from implementation to dissemination of findings).
The effectiveness of the treatments will be compared using multilevel modeling.
PAIs will be developed by conducting bootstrapped analyses to select variables that predict or moderate outcomes (Clinician Administered PTSD Scale severity ratings at Week 14), followed by leave-one-out cross-validation (i.e., jackknife) analyses to determine the magnitude of the predicted difference that results in each analysis representing that individuals "predicted advantage" (of one treatment over the others).
We hypothesize that individuals who receive PE will have better outcomes than those who receive pharmacotherapy alone, based on existing data (e.g., cross study effect size comparisons), but have planned the study and sample to maximize statistical power in all analyses.
Study Type
Interventional
Enrollment (Anticipated)
450
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Keith E Bredemeier, PhD
- Phone Number: 215-746-3310
- Email: kbred@pennmedicine.upenn.edu
Study Contact Backup
- Name: Michael Thase, MD
- Phone Number: 215-746-6680
- Email: thase@pennmedicine.upenn.edu
Study Locations
-
-
California
-
Menlo Park, California, United States, 94025
- Recruiting
- VA Palo Alto Healthcare System
-
Contact:
- Carmen McLean, PhD
- Phone Number: 26384 650-614-9997
- Email: Carmen.McLean4@va.gov
-
San Diego, California, United States, 92161
- Recruiting
- VA San Diego Healthcare System
-
Contact:
- Kathleen Grubbs, PhD
- Phone Number: 619-497-8404
- Email: Kathleen.Grubbs@va.gov
-
-
Pennsylvania
-
Coatesville, Pennsylvania, United States, 19320
- Recruiting
- Coatesville VA Medicial Center
-
Contact:
- Carmella Tress, PsyD
- Phone Number: 6838 610-384-7711
- Email: Carmella.Tress@va.gov
-
Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- Corporal Michael J. Crescenz VA Medical Center
-
Contact:
- Keith Bredemeier, Ph.D.
- Phone Number: 215-746-3310
- Email: kbred@pennmedicine.upenn.edu
-
Contact:
- Michael Thase, M.D.
- Phone Number: 2157466680
- Email: thase@pennmedicine.upenn.edu
-
-
Texas
-
Dallas, Texas, United States, 75216
- Recruiting
- VA North Texas Healthcare System
-
Contact:
- Geetha Shivakumar, MD
- Phone Number: 6 214-857-4279
- Email: Geetha.Shivakumar@va.gov
-
-
Wisconsin
-
Milwaukee, Wisconsin, United States, 53295
- Recruiting
- Milwaukee VA Medical Center
-
Contact:
- Sadie Larsen, PhD
- Phone Number: 46727 414-384-2000
- Email: Sadie.Larsen@va.gov
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- DSM-5 diagnosis of Posttraumatic Stress Disorder
- military veteran
- fluent in English
- willing to participate in PE, pharmacotherapy, or both
- capable of providing informed consent
Exclusion Criteria:
- suicidal ideation with intent and/or plan, or suicidal behavior in the past month
- active psychosis
- history of manic episode(s)
- a failed trial of Prolonged Exposure therapy or paroxetine and venlafaxine XR
- ongoing medical conditions or treatments that would contraindicate initiating these treatments (e.g., medications that have potential interactions with paroxetine and venlafaxine such as MAO inhibitors)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Prolonged Exposure Therapy
8-14 sessions of psychotherapy, each lasting 60-90 minutes, focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders
|
A form of cognitive-behavioral psychotherapy focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders
|
ACTIVE_COMPARATOR: Pharmacotherapy
20-60mg of paroxetine daily, or 75-300mg of venlafaxine XR daily
|
Standard dosing with paroxetine, a selectiveserotonin reuptake inhibitor that is FDA approved to treat PTSD and depression, or venlafaxine extended-release, a serotonin-norepinephrine reuptake inhibitor that is FDA approved to treat anxiety and depression
Other Names:
|
ACTIVE_COMPARATOR: Combined treatment (Prolonged Exposure and Pharmacotherapy)
8-14 sessions of psychotherapy, each lasting 60-90 minutes, focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders AND 20-60mg of paroxetine daily, or 75-300mg of venlafaxine XR daily
|
A form of cognitive-behavioral psychotherapy focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders
Standard dosing with paroxetine, a selectiveserotonin reuptake inhibitor that is FDA approved to treat PTSD and depression, or venlafaxine extended-release, a serotonin-norepinephrine reuptake inhibitor that is FDA approved to treat anxiety and depression
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change during active treatment on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time Frame: baseline to 14 weeks
|
The CAPS-5 is a structured clinical interview that assesses the presence and severity of PTSD symptoms.
Twenty items are rated on a 5-point scale from 0 (absent) to 4 (extremely/incapacitating).
Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity
|
baseline to 14 weeks
|
Change during follow-up on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time Frame: 14 weeks to 40 weeks
|
The CAPS-5 is a structured clinical interview that assesses the presence and severity of PTSD symptoms.
Twenty items are rated on a 5-point scale from 0 (absent) to 4 (extremely/incapacitating).
Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity
|
14 weeks to 40 weeks
|
Change during active treatment on the PTSD Checklist for DSM-5 (PCL-5)
Time Frame: baseline to 14 weeks
|
The PCL-5 is a 20-item self-report measure examining the presence and severity of recent PTSD symptoms using a 0 (not at all) to 4 (extremely) point Likert scale.
Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity.
|
baseline to 14 weeks
|
Change during follow-up on the PTSD Checklist for DSM-5 (PCL-5)
Time Frame: 14 weeks to 40 weeks
|
The PCL-5 is a 20-item self-report measure examining the presence and severity of recent PTSD symptoms using a 0 (not at all) to 4 (extremely) point Likert scale.
Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity.
|
14 weeks to 40 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change during active treatment on the Quick Inventory of Depressive Symptoms - clinician rated (QIDS-C)
Time Frame: baseline to 14 weeks
|
The QIDS is a structured interview that assesses presence and severity of depressive disorder symptoms.
Sixteen items are rated on a 0-3 scale and summed.
Total scores range from 0 to 27 (higher scores indicate greater depression symptom severity).
|
baseline to 14 weeks
|
Change during follow-up on the Quick Inventory of Depressive Symptoms - clinician rated (QIDS-C)
Time Frame: 14 weeks to 40 weeks
|
The QIDS is a structured interview that assesses presence and severity of depressive disorder symptoms.
Sixteen items are rated on a 0-3 scale and summed.
Total scores range from 0 to 27 (higher scores indicate greater depression symptom severity).
|
14 weeks to 40 weeks
|
Change during active treatment on the Patient Health Questionnaire depression module (PHQ-9)
Time Frame: baseline to 14 weeks
|
This self-report inventory consists of 9 items that assess depressive symptoms over the past 2 weeks using a scale from 0 (not at all) to 3 (nearly every).
Total scores range from 0 to 27, with higher scores indicating greater depression symptom severity.
|
baseline to 14 weeks
|
Change during follow-up on the Patient Health Questionnaire depression module (PHQ-9)
Time Frame: 14 weeks to 40 weeks
|
This self-report inventory consists of 9 items that assess depressive symptoms over the past 2 weeks using a scale from 0 (not at all) to 3 (nearly every).
Total scores range from 0 to 27, with higher scores indicating greater depression symptom severity.
|
14 weeks to 40 weeks
|
Change during active treatment on the Social and Occupational Functioning Assessment Scale (SOFAS)
Time Frame: baseline to 14 weeks
|
The SOFAS is a global clinical rating scale of current functioning, ranging from 0 to 100 (with higher scores indicated better functioning), which focuses on impairments in social and occupational functioning caused by physical and mental health problems (rated independent of symptom severity).
|
baseline to 14 weeks
|
Change during follow-up on the Social and Occupational Functioning Assessment Scale (SOFAS)
Time Frame: 14 weeks to 40 weeks
|
The SOFAS is a global clinical rating scale of current functioning, ranging from 0 to 100 (with higher scores indicated better functioning), which focuses on impairments in social and occupational functioning caused by physical and mental health problems (rated independent of symptom severity).
|
14 weeks to 40 weeks
|
Change during active treatment on the Veterans RAND 12-item Health Survey (VR-12)
Time Frame: baseline to 14 weeks
|
This brief self-report scale was developed (with modified items from the 36 item Short-Form Health Survey) and validated specifically for veterans to assess health-related quality of life, based on reported functioning in multiple domains (e.g., general health, social activities, role limitations).
Patients receive a physical component score and a mental component score, and both are scaled so that a score of 50 corresponds to the population average (higher scores indicate better quality of life).
|
baseline to 14 weeks
|
Change during follow-up on the Veterans RAND 12-item Health Survey (VR-12)
Time Frame: 14 weeks to 40 weeks
|
This brief self-report scale was developed (with modified items from the 36 item Short-Form Health Survey) and validated specifically for veterans to assess health-related quality of life, based on reported functioning in multiple domains (e.g., general health, social activities, role limitations).
Patients receive a physical component score and a mental component score, and both are scaled so that a score of 50 corresponds to the population average (higher scores indicate better quality of life).
|
14 weeks to 40 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 25, 2022
Primary Completion (ANTICIPATED)
February 15, 2025
Study Completion (ANTICIPATED)
February 15, 2025
Study Registration Dates
First Submitted
June 24, 2021
First Submitted That Met QC Criteria
July 2, 2021
First Posted (ACTUAL)
July 14, 2021
Study Record Updates
Last Update Posted (ACTUAL)
November 2, 2022
Last Update Submitted That Met QC Criteria
October 31, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Trauma and Stressor Related Disorders
- Stress Disorders, Traumatic
- Stress Disorders, Post-Traumatic
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Serotonin and Noradrenaline Reuptake Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors
- Paroxetine
- Venlafaxine Hydrochloride
Other Study ID Numbers
- 1620949-1
- CER-2020C1-19382 (OTHER_GRANT: Patient-Centered Outcomes Research Institute)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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