tDCS-Augmented Prolonged Exposure Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of a brain stimulation technique known as transcranial direct current stimulation, or tDCS, on the benefits of Prolonged Exposure therapy, or PE, which is an effective treatment for posttraumatic stress disorder, or PTSD. tDCS has been demonstrated to be safe and effective for influencing brain activity by passing a weak electrical current through the scalp. In this study, tDCS is provided in addition to PE treatment, through the National Crime Victim's Research and Treatment Center at MUSC, or the PTSD Clinical Team Clinic within the Ralph H. Johnson VA Medical Center.

Detailed Description
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This project implements a multiple baseline within-subject clinical trial design aiming to test whether tDCS targeting excitation of the medial prefrontal cortex (mPFC) can enhance a standard course of PE in a sample of adult civilians and Veterans (ages 18-65) who meet full DSM-5 criteria for chronic PTSD (i.e., > 3 months post-trauma; N = 20). All participants will receive a total of ten 60-min. sessions of manualized PE, preceded by 20 min. of either active or sham HD-tDCS. The stepped-wedge multiple baseline design features tDCS as a 2-level within-subject factor (Sham tDCS+PE vs. Active tDCS+PE), and between-subject comparisons based on stratified random assignment to cross-over from sham to active tDCS just prior to sessions 4 through 8. Strata will be defined by dichotomous classifications of possible confounds, including baseline severity (moderate vs. severe), psychotropic medication status (no vs. yes), and sex (female vs. male). The sample will consist of treatment-seeking civilian and Veteran participants referred by either of two of our consortium sites, including the National Crime Victim's Research and Treatment Center (NCVC) at MUSC, or the PTSD Clinical Team (PCT) at the Ralph H. Johnson VAMC, as well as community participants who respond to study advertisements.

Official Title
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tDCS-Augmented Prolonged Exposure Therapy for PTSD: A Multiple Baseline Within-Subject Clinical Trial

Conditions
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Posttraumatic Stress Disorder, PTSD, Anxiety, Depression

Intervention / Treatment
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* Device: Transcranial Direct Current Stimulation (tDCS)
* Behavioral: Prolonged Exposure Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65. Fluent in English. Diagnosis of chronic PTSD based on MINI for DSM-5 (> 3 mo. post-trauma) For Veterans recruited at the Ralph H. Johnson VA only: eligible to receive PE in the PCT clinic. Exclusion Criteria: Currently receiving psychotherapy for another anxiety- or stress-related condition. Unstable dose of psychotropic medications within 6 weeks prior to baseline assessment Medical condition that would contraindicate participation in treatment or assessment activities (e.g., severe cardiovascular problems). Pregnancy Current severe major depressive disorder Current, or history of bipolar disorder Current, or history of psychotic symptoms Serious suicidal risk Active neurological conditions, e.g., seizures, stroke, loss of consciousness or concussion Contraindications for tDCS: Metal in the head. Implanted brain medical devices.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be randomly assigned following stratification by baseline severity of PTSD symptoms, medication status, and sex to one of five clusters defined by the point of cross-over from sham to active tDCS administered just prior to PE therapy sessions, with the earliest cross-over occurring at session 4, and the latest at session 8.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cluster 1: Sham to active tDCS crossover at PE Session 4.<br>Participants in this cluster will receive 20 min. of sham tDCS prior to the PE sessions 1-3, and 20 min. of active tDCS prior to PE sessions 4-10. | Device: Transcranial Direct Current Stimulation (tDCS)<br>* Participants will receive 20 min. of either sham or active tDCS prior to PE sessions using a 1 x 1 tDCS device with a ring electrode configuration that allows relatively excitatory and focal stimulation of the dorsomedial prefrontal cortex (dmPFC). Electrodes consist of sponges in a silicone rubber holder with a metal mesh conductor saturated with normal saline. A center anode (2.5 cm diameter) and a ring-shaped cathode (diameter inner/outer: 9.2/11.50 cm) will be centered over the dmPFC, with the anode placed the midline at 15% of the Fz to FPz distance. Active stimulation will commence with a 15 sec. ramping up period to target current (1.5 mA), followed by constant current for 20 min., and a 15 sec. ramping down period. For all sham sessions, stimulation will be immediately ramped down over a 15 sec. period following the initial ramping up period, and subsequently ramped up over 15 sec. prior to the final ramping down period.<br>* Other names: Soterix Medical 1 x 1 Transcranial Electrical Stimulator (tES);Behavioral: Prolonged Exposure Therapy<br>* All participants will receive 10 weekly sessions of standard Prolonged Exposure Therapy, or PE, which is a gold standard trauma-focused cognitive behavioral treatment for PTSD. The first sessions (1-2) predominately consist of psychoeducation about PTSD and the rationale for treatment, whereas subsequent sessions (3-10) consist of imaginal and in vivo exposure, involving repeated, prolonged, systematic, and deliberate practice approaching trauma reminders, as well as cognitive and emotional processing reactions to an index trauma memory.<br>* Other names: Trauma-focused therapy;|
| Active Comparator: Cluster 2: Sham to active tDCS crossover at PE Session 5.<br>Participants in this cluster will receive 20 min. of sham tDCS prior to the PE sessions 1-4, and 20 min. of active tDCS prior to PE sessions 5-10. | Device: Transcranial Direct Current Stimulation (tDCS)<br>* Participants will receive 20 min. of either sham or active tDCS prior to PE sessions using a 1 x 1 tDCS device with a ring electrode configuration that allows relatively excitatory and focal stimulation of the dorsomedial prefrontal cortex (dmPFC). Electrodes consist of sponges in a silicone rubber holder with a metal mesh conductor saturated with normal saline. A center anode (2.5 cm diameter) and a ring-shaped cathode (diameter inner/outer: 9.2/11.50 cm) will be centered over the dmPFC, with the anode placed the midline at 15% of the Fz to FPz distance. Active stimulation will commence with a 15 sec. ramping up period to target current (1.5 mA), followed by constant current for 20 min., and a 15 sec. ramping down period. For all sham sessions, stimulation will be immediately ramped down over a 15 sec. period following the initial ramping up period, and subsequently ramped up over 15 sec. prior to the final ramping down period.<br>* Other names: Soterix Medical 1 x 1 Transcranial Electrical Stimulator (tES);Behavioral: Prolonged Exposure Therapy<br>* All participants will receive 10 weekly sessions of standard Prolonged Exposure Therapy, or PE, which is a gold standard trauma-focused cognitive behavioral treatment for PTSD. The first sessions (1-2) predominately consist of psychoeducation about PTSD and the rationale for treatment, whereas subsequent sessions (3-10) consist of imaginal and in vivo exposure, involving repeated, prolonged, systematic, and deliberate practice approaching trauma reminders, as well as cognitive and emotional processing reactions to an index trauma memory.<br>* Other names: Trauma-focused therapy;|
| Active Comparator: Cluster 3: Sham to active tDCS crossover at PE Session 6<br>Participants in this cluster will receive 20 min. of sham tDCS prior to the PE sessions 1-5, and 20 min. of active tDCS prior to PE sessions 6-10. | Device: Transcranial Direct Current Stimulation (tDCS)<br>* Participants will receive 20 min. of either sham or active tDCS prior to PE sessions using a 1 x 1 tDCS device with a ring electrode configuration that allows relatively excitatory and focal stimulation of the dorsomedial prefrontal cortex (dmPFC). Electrodes consist of sponges in a silicone rubber holder with a metal mesh conductor saturated with normal saline. A center anode (2.5 cm diameter) and a ring-shaped cathode (diameter inner/outer: 9.2/11.50 cm) will be centered over the dmPFC, with the anode placed the midline at 15% of the Fz to FPz distance. Active stimulation will commence with a 15 sec. ramping up period to target current (1.5 mA), followed by constant current for 20 min., and a 15 sec. ramping down period. For all sham sessions, stimulation will be immediately ramped down over a 15 sec. period following the initial ramping up period, and subsequently ramped up over 15 sec. prior to the final ramping down period.<br>* Other names: Soterix Medical 1 x 1 Transcranial Electrical Stimulator (tES);Behavioral: Prolonged Exposure Therapy<br>* All participants will receive 10 weekly sessions of standard Prolonged Exposure Therapy, or PE, which is a gold standard trauma-focused cognitive behavioral treatment for PTSD. The first sessions (1-2) predominately consist of psychoeducation about PTSD and the rationale for treatment, whereas subsequent sessions (3-10) consist of imaginal and in vivo exposure, involving repeated, prolonged, systematic, and deliberate practice approaching trauma reminders, as well as cognitive and emotional processing reactions to an index trauma memory.<br>* Other names: Trauma-focused therapy;|
| Active Comparator: Cluster 4: Sham to active tDCS crossover at PE Session 7.<br>Participants in this cluster will receive 20 min. of sham tDCS prior to the PE sessions 1-6, and 20 min. of active tDCS prior to PE sessions 7-10. | Device: Transcranial Direct Current Stimulation (tDCS)<br>* Participants will receive 20 min. of either sham or active tDCS prior to PE sessions using a 1 x 1 tDCS device with a ring electrode configuration that allows relatively excitatory and focal stimulation of the dorsomedial prefrontal cortex (dmPFC). Electrodes consist of sponges in a silicone rubber holder with a metal mesh conductor saturated with normal saline. A center anode (2.5 cm diameter) and a ring-shaped cathode (diameter inner/outer: 9.2/11.50 cm) will be centered over the dmPFC, with the anode placed the midline at 15% of the Fz to FPz distance. Active stimulation will commence with a 15 sec. ramping up period to target current (1.5 mA), followed by constant current for 20 min., and a 15 sec. ramping down period. For all sham sessions, stimulation will be immediately ramped down over a 15 sec. period following the initial ramping up period, and subsequently ramped up over 15 sec. prior to the final ramping down period.<br>* Other names: Soterix Medical 1 x 1 Transcranial Electrical Stimulator (tES);Behavioral: Prolonged Exposure Therapy<br>* All participants will receive 10 weekly sessions of standard Prolonged Exposure Therapy, or PE, which is a gold standard trauma-focused cognitive behavioral treatment for PTSD. The first sessions (1-2) predominately consist of psychoeducation about PTSD and the rationale for treatment, whereas subsequent sessions (3-10) consist of imaginal and in vivo exposure, involving repeated, prolonged, systematic, and deliberate practice approaching trauma reminders, as well as cognitive and emotional processing reactions to an index trauma memory.<br>* Other names: Trauma-focused therapy;|
| Active Comparator: Cluster 5: Sham to active tDCS crossover at PE Session 8.<br>Participants in this cluster will receive 20 min. of sham tDCS prior to the PE sessions 1-7, and 20 min. of active tDCS prior to PE sessions 8-10. | Device: Transcranial Direct Current Stimulation (tDCS)<br>* Participants will receive 20 min. of either sham or active tDCS prior to PE sessions using a 1 x 1 tDCS device with a ring electrode configuration that allows relatively excitatory and focal stimulation of the dorsomedial prefrontal cortex (dmPFC). Electrodes consist of sponges in a silicone rubber holder with a metal mesh conductor saturated with normal saline. A center anode (2.5 cm diameter) and a ring-shaped cathode (diameter inner/outer: 9.2/11.50 cm) will be centered over the dmPFC, with the anode placed the midline at 15% of the Fz to FPz distance. Active stimulation will commence with a 15 sec. ramping up period to target current (1.5 mA), followed by constant current for 20 min., and a 15 sec. ramping down period. For all sham sessions, stimulation will be immediately ramped down over a 15 sec. period following the initial ramping up period, and subsequently ramped up over 15 sec. prior to the final ramping down period.<br>* Other names: Soterix Medical 1 x 1 Transcranial Electrical Stimulator (tES);Behavioral: Prolonged Exposure Therapy<br>* All participants will receive 10 weekly sessions of standard Prolonged Exposure Therapy, or PE, which is a gold standard trauma-focused cognitive behavioral treatment for PTSD. The first sessions (1-2) predominately consist of psychoeducation about PTSD and the rationale for treatment, whereas subsequent sessions (3-10) consist of imaginal and in vivo exposure, involving repeated, prolonged, systematic, and deliberate practice approaching trauma reminders, as well as cognitive and emotional processing reactions to an index trauma memory.<br>* Other names: Trauma-focused therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician-Rated PTSD Symptom Severity | Clinician-administered PTSD Symptom Scale Interview for DSM-5 (PSSI-5). Total scores range from 0 to 80, with higher scores indicating greater severity of PTSD symptoms. | Pre-treatment (baseline), post-treatment (12 weeks post-baseline), and 1-month follow-up (16 weeks post-baseline) | 
| Change in Self-Reported PTSD Symptom Severity | Self-report scores on the PTSD Symptom Checklist for DSM-5 (PCL-5) Total scores range from 0 to 80, with higher scores indicating greater severity of PTSD symptoms. | Pre-treatment (baseline), post-treatment (12 weeks post-baseline), and 1-month follow-up (16 weeks post-baseline) | 
| Change in Self-Reported Post-traumatic Cognitions | Self-report scores on the Post-traumatic Cognitions Inventory (PTCI-9) Total scores range from 9 to 63, with high scores indicating greater endorsement of common and problematic trauma-related beliefs. | Pre-treatment (baseline), post-treatment (12 weeks post-baseline), and 1-month follow-up (16 weeks post-baseline) | 
| Change in Depression Symptoms | Self-report scores on the Beck Depression Inventory, 2nd Edition (BDI-II) Total scores range from 0 to 63, with higher scores indicating greater severity of depression symptoms. | Pre-treatment (baseline), post-treatment (12 weeks post-baseline), and 1-month follow-up (16 weeks post-baseline) | 
| Change in Anxiety Symptoms | Self-report scores on the Beck Anxiety Inventory (BAI) Total scores range from 0 to 63, with higher scores indicating greater severity of anxiety symptoms. | Pre-treatment (baseline), post-treatment (12 weeks post-baseline), and 1-month follow-up (16 weeks post-baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within- and Between-Session Change in Trauma-Related Emotional Distress | Self-reported in-session Subjective Units of Distress Scale (SUDS) Peak distress among repeated ratings obtained during therapy sessions from 0 = no distress to 100 = extreme distress. Ratings will be obtained up to 13 times at each weekly Prolonged Exposure therapy session, for 10 weeks. | During weekly therapy sessions 1-10, for 10 weeks from baseline. | 
| Within- and Between-Session Change in Heart Rate | Continuously recorded in-session heart rate Heart rate will be continuously recorded during each weekly Prolonged Exposure therapy session, for 10 weeks. | During weekly therapy sessions 1-10, for 10 weeks from baseline. | 
| Within- and Between-Session Change in Physiological Activation | Continuously recorded in-session skin conductance levels Skin conductance levels will be continuously monitored during each weekly Prolonged Exposure therapy session, for 10 weeks. | During weekly therapy sessions 1-10, for 10 weeks from baseline. | 
| Between-Session Change in Trauma Memory Engagement and Emotional Processing | Therapist-report scores on the Prolonged Exposure Therapist Questionnaire Total scores range from 0 to 35, with higher scores indicating greater retrieval, processing, and meaning making during imaginal revisiting of the index trauma memory. | During weekly therapy sessions 1-10, for 10 weeks from baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-invasive brain stimulation, Transcranial direct current stimulation, Exposure therapy, Prolonged Exposure, Civilians, Veterans, Trauma, Posttraumatic stress disorder, PTSD