Circadian Influence on Prolonged Exposure Therapy for PTSD

Not Applicable

Recruiting

• Conditions: PTSD
• Interventions: Behavioral: Prolonged Exposure Therapy for Posttraumatic Stress Disorder

• Registration Number: NCT05453162
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

Proposed research will examine time-of-day effects on trauma-related fear extinction using Prolonged Exposure Therapy (PE) telemedicine for Posttraumatic Stress Disorder (PTSD) in the National Center for PTSD (NCPTSD). The primary mechanistic outcome measure will be change in psychophysiological reactivity to script-driven imagery (SDI-PR) measured, in person, at pre-treatment, after 5 PE sessions (mid-treatment), and after all 10 PE sessions (post-treatment). A secondary mechanistic outcome will be session-to-session reduction in peak subjective units of distress (SUDS) ratings to imaginal exposures. The primary clinical outcome will be change in Clinican Administered PTSD Scale (CAPS-5) severity score; a secondary clinical outcome will be session-to-session reduction in self-reported PTSD symptoms using the PTSD checklist (PCL-5). Participants meeting inclusion criteria (described below) will be randomized to either PE sessions that begin from 07:00 to a time no later than 2 hours past a participant's customary rise time, or to the last treatment session of the day beginning at 16:00 or later (26 per arm). Participants will complete daily at-home imaginal-exposure homework within the same time frame as their PE sessions are scheduled, i.e., within 2 hours of awakening for morning (AM) group and between 16:00 and 2 hours before bedtime for late afternoon (PM) group.

Detailed Description

Proposed research will examine time-of-day effects on trauma-related fear extinction using PE therapy for PTSD in the National Center for PTSD (NCPTSD). The primary mechanistic outcome measure will be change in SDI-PR; a secondary mechanistic outcome will be session-to-session reduction in peak SUDS ratings to imaginal exposures. The primary clinical outcome will be change in CAPS-5 severity score; a secondary clinical outcome will be session-to-session reduction in self-reported PTSD symptoms (PCL-5). Participants meeting inclusion criteria (described below) will be randomized to either PE sessions that begin from 07:00 to a time no later than 2 hours past a participant's customary rise time, or to the last treatment session of the day beginning at 16:00 or later. Participants will complete daily at-home imaginal-exposure homework within the same time frame as their PE sessions are scheduled (i.e., within 2 hours of awakening for morning group and between 16:00 and 2 hours before bedtime for late afternoon group). The assessment schedule will be identical for all participants. Participants who meet study inclusion criteria at screening will first begin a 7-day, pre-study sleep-monitoring period with wrist actigraphy, sleep diaries and completion of a diurnal profile of salivary cortisol levels. Trauma-related fear will be assessed using the standard SDI procedures detailed below at pre-treatment, after 5 PE sessions (mid-treatment), and after all 10 PE sessions (post-treatment). The CAPS-5 will be administered at these same times. PCL-5 measurements will be obtained at each treatment session and SUDs will be obtained during all treatment sessions that include imaginal exposure (sessions 3-8). All SDI sessions will be carried out at a standardized time of day in the late-afternoon (15:00-17:00). PE treatment will be administered at a targeted rate of once per week. At each PE and assessment session, pre-session saliva samples will be obtained for cortisol measurement and normalized using the diurnal profile of cortisol obtained during the sleep-assessment week. Participants will wear the wrist actigraph and complete sleep diaries throughout PE. The diurnal cortisol profile will be repeated at the post-treatment assessment.

Study Timeline

• Study First Submitted: 2022-06-29
• Study Start: 2022-07-01
• Study First Submitted QC: 2022-07-06
• Study First Posted: 2022-07-12
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-25
• Last Update Posted: 2023-02-28
• Primary Completion: 2024-04-30
• Study Completion: 2024-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. a diagnosis of PTSD as defined by DSM-5, with a minimum CAPS severity score of 26
2. interest in starting a course of PE
3. availability for appointments at that will either begin from 07:00 to a time no longer than 2 hours past their customary rise time, or to the last treatment session of the day beginning at 16:00 or later
4. Age range of 25-45
5. Veteran
6. Intermediate ("neither type") score of 42-58 on the Morningness-Eveningness Questionnaire (MEQ).

Exclusion Criteria

1. current or past history of bipolar I disorder, schizophrenic or other psychotic disorders,
2. current organic brain disorder including moderate to severe traumatic brain injury
3. factitious disorder or malingering
4. pregnancy
5. current substance use disorder
6. active risk of harm to self or others
7. evidence of clinically significant hepatic or renal disease or any other acute or unstable medical condition that might interfere with safe conduct of the study
8. current participation in trauma-focused cognitive-behavioral therapy (e.g., Cognitive Processing Therapy, Written Exposure Therapy, Eye Movement Desensitization and Reprocessing Therapy)
9. prior treatment with an adequate dose of PE (i.e., 8 or more sessions)
10. having no memory of their traumatic event
11. daily, or as-needed, use of benzodiazepines.
12. methadone or suboxone maintenance therapy for past opioid addiction
13. diagnosis of Cushing's disease, Addison's disease or use of medications that target cortisol directly such as those used to treat Cushing's disease [ketoconazole, mitotane (Lysodren), metyrapone (Metopirone), and Mifepristone (Korlym, Mifeprex)], those used to treat Addison's disease [Hydrocortisone (Cortef), prednisone or methylprednisolone], as well as cortisone or dexamethasone.
14. persons habitually waking up after 8 AM or who would habitually awaken so early that more than 2 h would elapse before a morning PE session could occur
15. Non-exclusionary psychotropic medications must have been stable for 3 months prior to enrollment and remain stable throughout participation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Late afternoon PE	Prolonged Exposure Therapy for Posttraumatic Stress Disorder	26 participants randomized to 10 weekly PE sessions in late afternoon (16:00 or later) with homework exposures occurring occur at this same time of day.
Early morning PE	Prolonged Exposure Therapy for Posttraumatic Stress Disorder	26 participants randomized to 10 weekly PE sessions in early morning (between 07:00-10:00) with homework exposures occurring occur at this same time of day.

Primary Outcome Measures

Name	Time	Method
Psychophysiological reactivity to script-driven imagery (SDI-PR): Primary Mechanistic Outcome	Between days 29-34, mid-treatment	This primary mechanistic outcome is a unitary discriminant canonical variable measuring psychophysiological reactivity while listening to personalized recorded scripts describing an index trauma.
Psychophysiological reactivity to script-driven imagery (SDI-PR: )Primary Mechanistic Outcome	Between days 64-71, post-treatment	This primary mechanistic outcome is a unitary discriminant canonical variable measuring psychophysiological reactivity while listening to personalized recorded scripts describing an index trauma.
Clinician-Administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition (CAPS-5): Primary Clinical Outcome	Between days -7 to -1, Baseline	This primary clinical outcome 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.
CAPS-5: Primary Clinical Outcome	Between days 64-71, post-treatment	This primary clinical outcome 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.

Secondary Outcome Measures

Name	Time	Method
Subjective Units of Distress (SUDS): Secondary Mechanistic Outcome	Day 14 Peak SUDS during PE therapy session 3	A rating scale from 0 to 100 where zero represents no distress at all and 100 represents very extreme distress, fear, or anxiety. SUDS ratings are subjective and different individuals may rate the same situation differently. An individual anchors their own ratings with personal recollection of situations considered "No Distress" to "Moderate" to "Extreme Distress".
SUDS: Secondary Mechanistic Outcome	Day 63 Peak SUDS during PE therapy session 10	A rating scale from 0 to 100 where zero represents no distress at all and 100 represents very extreme distress, fear, or anxiety. SUDS ratings are subjective and different individuals may rate the same situation differently. An individual anchors their own ratings with personal recollection of situations considered "No Distress" to "Moderate" to "Extreme Distress".
PCL-5: PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition: Secondary Clinical Outcome	Day 0 PCL-5 score at PE therapy session 1	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).
PCL-5: Secondary Clinical Outcome	Day 63 PCL-5 score at PE therapy session 10	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).

Trial Locations

Locations (1)

VA Boston Healthcare System; 🇺🇸 Boston, Massachusetts, United States