Clinical trial NCT04961190: A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD
Official title: A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD: What Works Best, and for Whom
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Posttraumatic Stress Disorder
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Corporal Michael J. Crescenz VA Medical Center
name: Coatesville VA Medical Center
name: Milwaukee VA Medical Center
name: North Texas Veterans Healthcare System
name: San Diego Veterans Healthcare System
name: VA Palo Alto Health Care System
name: Birmingham VA Health Care System
First posted: 2021-07-14
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 = 300) 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).

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 = 300) 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change during active treatment on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
timeFrame: baseline to 14 weeks
measure: Change during follow-up on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
timeFrame: 14 weeks to 40 weeks
measure: Change during active treatment on the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: baseline to 14 weeks
measure: Change during follow-up on the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: 14 weeks to 40 weeks
Secondary outcomes:
measure: Change during active treatment on the Quick Inventory of Depressive Symptoms - clinician rated (QIDS-C)
timeFrame: baseline to 14 weeks
measure: Change during follow-up on the Quick Inventory of Depressive Symptoms - clinician rated (QIDS-C)
timeFrame: 14 weeks to 40 weeks
measure: Change during active treatment on the Patient Health Questionnaire depression module (PHQ-9)
timeFrame: baseline to 14 weeks
measure: Change during follow-up on the Patient Health Questionnaire depression module (PHQ-9)
timeFrame: 14 weeks to 40 weeks
measure: Change during active treatment on the Social and Occupational Functioning Assessment Scale (SOFAS)
timeFrame: baseline to 14 weeks
measure: Change during follow-up on the Social and Occupational Functioning Assessment Scale (SOFAS)
timeFrame: 14 weeks to 40 weeks
measure: Change during active treatment on the Veterans RAND 12-item Health Survey (VR-12)
timeFrame: baseline to 14 weeks
measure: Change during follow-up on the Veterans RAND 12-item Health Survey (VR-12)
timeFrame: 14 weeks to 40 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA Healthcare System
state: Alabama
city: Menlo Park
country: United States
facility: VA Palo Alto Healthcare System
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System
state: California
city: Coatesville
country: United States
facility: Coatesville VA Medicial Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Corporal Michael J. Crescenz VA Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: VA North Texas Healthcare System
state: Texas
city: Milwaukee
country: United States
facility: Milwaukee VA Medical Center
state: Wisconsin
Study officials:
References:
citation: Bredemeier K, Larsen S, Shivakumar G, Grubbs K, McLean C, Tress C, Rosenfield D, DeRubeis R, Xu C, Foa E, Morland L, Pai A, Tsao C, Crawford J, Weitz E, Mayinja L, Feler B, Wachsman T, Lupo M, Hooper V, Cook R, Thase M. A comparison of prolonged exposure therapy, pharmacotherapy, and their combination for PTSD: What works best and for whom; study protocol for a randomized trial. Contemp Clin Trials. 2022 Aug;119:106850. doi: 10.1016/j.cct.2022.106850. Epub 2022 Jul 13.