Mechanisms Underlying the Efficacy of Prolonged Exposure

Posttraumatic Stress Disorder Clinical Trial

Official title:

Mechanisms Underlying the Efficacy of Prolonged Exposure

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05663151
• Other study ID #: 1577670
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: December 2022
• Source: VA Boston Healthcare System
• Contact: Suzanne Pineles, PhD
• Phone: 857-364-5906
• Email: suzanne.pineles[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this research is to collect pilot data that demonstrates that proposed neural, psychophysiological and subjective markers measured before, during, and after treatment change over the course of Prolonged Exposure therapy (PE) for posttraumatic stress disorder (PTSD). The aims of the study are to: (1) examine theoretically informed mechanisms as pre-treatment predictors of PE treatment efficacy, (2) characterize how neural, psychophysiological, and subjective markers measured before, during, and after treatment change over the course of PE, and (3) examine proposed mechanisms of change as measures of PE treatment efficacy. This is a longitudinal study of predictors of exposure therapy efficacy that will be conducted within the context of a standard 10 session PE treatment trial, with independent multimodal assessment batteries administered at pre-treatment, mid-treatment, post-treatment, and at 1-month follow-up. This data will be used to support a future NIMH and/or VA grant submission.

Description:

Proposed research sets to collect pilot data to examine how the proposed neural, psychophysiological and subjective markers measured before, during, and after treatment change over the course of Prolonged Exposure (PE) therapy for posttraumatic stress disorder (PTSD). Fifty participants will be screened with the goal of obtaining 15 participants to complete the study. Participants will complete ten 60-minute sessions of PE. During each PE session, participants will be outfitted with a NINscan device to record psychophysiological measures including skin conductance, heart rate, and facial EMG, as well as neural measures of LPFC activity. Multimodal assessment batteries will be scheduled to take place at pre-treatment, mid-treatment (i.e., post session 5), post-treatment (i.e., post-session 10), and at 1-month follow-up. These sessions will include a battery of self-report measures, clinician-administered diagnostic interviews, and script-driven imagery (SDI) procedures with physiologic and neural recordings. The primary outcome measure will be PTSD symptom change on the CAPS-5 and the secondary outcome measures will be a) change in self-reported symptom severity, b) premature treatment dropout, and c) change in psychophysiological reactivity and LPFC activity during the SDI procedures. This proposed research will inform theoretical models of exposure therapy efficacy, with the goal of enhancing prolonged exposure therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

1. a diagnosis of PTSD as defined by DSM-5 (as indicated by meeting diagnostic criteria on the CAPS-5)

2. interest in starting PE (as indicated during the informed consent process)

3. Veteran

Exclusion Criteria:

1. Current or past history of schizophrenic or other psychotic disorders,

2. Untreated Bipolar Disorder or a history of a manic/mixed episode within the last 6 months,

3. Severe traumatic brain injury,

4. Major neurological problems,

5. Current substance use disorder,

6. Active risk to self or others,

7. Current participation in cognitive-behavioral therapy,

8. Previously received > 2 sessions of Prolonged Exposure, and

9. Having no memory of their traumatic event.

10. For participants who are currently prescribed psychotropic medication, they will be eligible for the study provided medication use has been stable for 2 months prior to enrollment and remains stable throughout participation

Related Conditions & MeSH terms

• Posttraumatic Stress Disorder
• Stress Disorders, Post-Traumatic

Intervention

Behavioral:
• Prolonged Exposure Therapy for Posttraumatic Stress Disorder
Participation will occur throughout 17 weeks over 15 separate visits during which 10, 60-minute sessions of PE will take place. Session 1 of PE will focus on psychoeducation. Session 2 of PE will involve a continuation of psychoeducation and rationale for exposure as well as the collaborative construction of the in vivo exposure hierarchy. After session 2, participants will begin homework where they are instructed to confront situations on their hierarchy. Starting in session 3 of PE, participants will begin imaginal exposures to their worst trauma memory. This involves the participant recounting and visualizing the trauma memory aloud with the clinician in the room for 30-40 minutes. The session will end with 15-20 minutes of processing the imaginal exposure. Participants will continue in-session imaginal exposures until the end of treatment. Throughout the treatment, participants will listen to a recording of their imaginal exposure and engage in in vivo exposures daily.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
VA Boston Healthcare System	National Center for PTSD

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Clinician Administered PTSD Scale for DSM-5 (CAPS-5)	The primary clinical outcome, CAPS-5, is the gold standard clinical interview for assessing PTSD severity. In CAPS-5, each of the 20 symptoms of PTSD is rated on a 5-point severity scale ranging from 0 (absent) to 4 (extreme). Total scores range from 0 to 80.	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	PTSD Checklist for DSM-5 (PCL-5)	Self-ratings of how much one is bothered by each of the 20 symptoms of PTSD on a 5-point severity scale ranging from 0 (Not at all) to 4 (extremely)	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	QIDS-SR (93)	Used to measure severity of depressive symptoms. provides equivalent weightings (0-3) for each symptom item, gives clearly stated anchors that estimate the frequency and severity of symptoms, and includes all items required to diagnose a major depressive episode (approximately 5 minutes)	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	Prefrontal cortical activity during script-driven imagery (SDI)	Prefrontal cortical (PFC) activity will be monitored during SDI procedures using NINscan portable brain and physiologic monitoring system via near infrared spectroscopy (NIRS) of the medial and lateral PFC. NIRS yields concentrations of oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin that can be used to assess cortical activation. Various portions of PFC (e.g. Brodmann areas 10, 46, 44, 45 and 47) have been shown to activate and/or deactivate during script-driven imagery (SDI) of an index trauma in persons with PTSD and to be associated with better PE outcome. NIRS data will be converted to quantitative oxy-Hb, deoxy-Hb, and total-Hb using the modified Beer-Lambert law. Changes in quantitative hemodynamic measure (oxy-Hb, deoxy-Hb, total-Hb) will be compared between 30 s of trauma-related SDI and their baseline epochs (30 s of silence preceding the respective script).	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	Change in electrocardiography (ECG) and heart rate variability (HRV) during script driven imagery (SDI)	ECG will be monitored during SDI procedures using NINscan portable brain and physiologic monitoring system. ECG will be collected continuously and the relative change calculated by subtracting the average ECG level for the 5 seconds immediately preceding SDI onset from the maximum level within 1 to 5 seconds after SDI onset. Heart rate variability (HRV) will be calculated form 5-minute epochs during baseline, calculating the standard deviation of all NN intervals, and comparing them to 5-minute intervals after onset of SDI. The ECG and HRV signals will be assessed individually and also in combination using posterior probability scores. Changes in ECG and HRV have been shown to indicate differential sympathetic reactivity in persons with PTSD versus controls.	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	Change in skin conductance (SC) during script-driven imagery (SDI)	SC will be monitored during SDI procedures using NINscan portable brain and physiologic monitoring system. SC level for the 5 seconds immediately preceding SDI onset from the maximum level within 1 to 5 seconds after SDI onset. This response window is selected to reduce the likelihood that response scores would be contaminated by spontaneous SC fluctuations. The signals will be assessed individually and also in combination using posterior probability scores. Changes in SC signals have been shown to indicate differential sympathetic reactivity in persons with PTSD versus controls.	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	Change in electromyography (EMG) during script-driven imagery (SDI)	Electromyography of the corrugator muscle will be monitored during SDI procedures using NINscan portable brain and physiologic monitoring system. An EMG response (EMGR) score will be calculated by subtracting the average EMG level for the 5 seconds immediately preceding SDI onset from the maximum level during SDI. The signals will be assessed individually and also in combination using posterior probability scores. Changes in corrugator EMG have been shown to indicate differential sympathetic reactivity in persons with PTSD versus controls.	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	Change in respirometry during script-driven imagery (SDI)	Changes in respirometry will be monitored during SDI procedures using NINscan portable brain and physiologic monitoring system. Average frequency and signal amplitude during baseline and SDI exposure epochs will be compared to calculate the relative change in respirometry. Changes in respirometry have been shown to indicate differential sympathetic reactivity in persons with PTSD versus controls.	Given during screening session, pre-treatment, mid-treatment (post session 5 in week 5 of treatment), post-treatment (post session 10 in week 10 of treatment), and at 1-month follow up.
Secondary	Premature treatment dropout	Maintenance of active participation or dropout from the treatment will be assessed.	Given at pre-treatment and mid-treatment (post session 5 in week 5 of treatment).