PTSDNCT05453162

Circadian Influence on Prolonged Exposure Therapy for PTSD

A study testing Prolonged Exposure Therapy for Posttraumatic Stress Disorder in people with PTSD, run by Massachusetts General Hospital at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: PTSD
What is being tested?: Prolonged Exposure Therapy for Posttraumatic Stress Disorder
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 52 participants
Where: 1 siteUnited States
Study dates: 1 Jul 2022to 1 Sep 2026
Phase: Interventional
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

a diagnosis of PTSD as defined by DSM-5, with a minimum CAPS severity score of 26, a minimum PCL-5 score of 31, or a score of 2 or above on CAPS-5 Item B2 (concerning distressing dreams)
interest in starting a course of PE
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
Age range of 18-70
A Morningness-Eveningness Questionnaire (MEQ) score above 25.
Non-exclusionary psychotropic medications must have been stable for 3 weeks prior to Screening/Assessment with intention to remain stable throughout participation.

Who cannot join

current or past history of bipolar I disorder, schizophrenic or other psychotic disorders,
current organic brain disorder including moderate to severe traumatic brain injury
factitious disorder or malingering
pregnant or planning to become pregnant in the next four months at time of screening [if a participant does become pregnant during study procedures, the situation will be reviewed on a case-by-case basis and the participant's wishes will be considered in deciding whether the participant will continue with the study or withdraw.]
current moderate or severe substance use disorder with symptoms present within the past three months
diagnosed moderate to severe sleep apnea, narcolepsy, periodic limb movement, or restless legs syndrome that result in daytime sleepiness indicated by Epworth Sleepiness Scale (ESS) above 10

Show all 15Show fewer

active risk of harm to self or others
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
current participation in trauma-focused cognitive-behavioral therapy (e.g., Cognitive Processing Therapy, Written Exposure Therapy, Eye Movement Desensitization and Reprocessing Therapy)
prior treatment with an adequate dose of PE (i.e., 8 or more sessions) to the traumatic event that would be the index trauma for treatment in the study
having no memory of their traumatic event
daily use of benzodiazepines
methadone or suboxone maintenance therapy for past opioid addiction
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.
persons who would habitually awaken so early that more than 2 h would elapse before a morning PE session could occur; or those who engage in habitual shiftwork or transmeridian travel

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Boston Healthcare System
Boston, Massachusetts, 02130-4817

Other trials in United States

About this study

Official title: Circadian Influence on Fear Extinction Resulting From Prolonged Exposure Therapy for PTSD

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.

Read the 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.

Conditions: PTSD
Being tested: Prolonged Exposure Therapy for Posttraumatic Stress Disorder
Keywords: PTSD, Circadian, Exposure Therapy, Sleep, Cortisol
Medical subject headings: Stress Disorders, Post-Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Prolonged Exposure Therapy for Posttraumatic Stress DisorderBehavioural
Manualized procedures deliver ten 90-minute sessions targeted to occur weekly and administered via tele-health with the same study therapist. Session 1 will focus on psychoeducation. Session 2 involves construction of the in vivo exposure hierarchy. Sessions 3-10 focus on in-session imaginal exposures to the worst trauma memory for 45-60 min followed by 15-20 min of processing the imaginal exposure. For homework, participants will be instructed to confront situations on their hierarchy on a daily basis using recording of their imaginal exposure. Subjective Units of Distress (SUDS) ratings will be taken throughout imaginal exposure exercises.

Study groups in NCT05453162
Study group	Role	What they receive
Early morning PE	Experimental	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. Receives: Behavioral: Prolonged Exposure Therapy for Posttraumatic Stress Disorder
Late afternoon PE	Experimental	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. Receives: Behavioral: Prolonged Exposure Therapy for Posttraumatic Stress Disorder

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (18)

Subjective Units of Distress (SUDS): Secondary Mechanistic Outcome
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".
Measured: Day 14 Peak SUDS during PE therapy session 3
SUDS: Secondary Mechanistic Outcome
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".
Measured: Day 21 Peak SUDS during PE therapy session 4
SUDS: Secondary Mechanistic Outcome
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".
Measured: Day 28 Peak SUDS during PE therapy session 5
SUDS: Secondary Mechanistic Outcome
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".
Measured: Day 35 Peak SUDS during PE therapy session 6
SUDS: Secondary Mechanistic Outcome
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".
Measured: Day 42 Peak SUDS during PE therapy session 7
SUDS: Secondary Mechanistic Outcome
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".
Measured: Day 49 Peak SUDS during PE therapy session 8
SUDS: Secondary Mechanistic Outcome
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".
Measured: Day 56 Peak SUDS during PE therapy session 9
SUDS: Secondary Mechanistic Outcome
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".
Measured: Day 63 Peak SUDS during PE therapy session 10
PCL-5: PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition: Secondary Clinical Outcome
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).
Measured: Day 0 PCL-5 score at PE therapy session 1
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 7 PCL-5 score at PE therapy session 2
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 14 PCL-5 score at PE therapy session 3
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 21 PCL-5 score at PE therapy session 4
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 28 PCL-5 score at PE therapy session 5
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 35 PCL-5 score at PE therapy session 6
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 42 PCL-5 score at PE therapy session 7
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 49 PCL-5 score at PE therapy session 8
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 56 PCL-5 score at PE therapy session 9
PCL-5: Secondary Clinical Outcome
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).
Measured: Day 63 PCL-5 score at PE therapy session 10

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 20221 Sep 2026

First posted12 Jul 2022
Study start1 Jul 2022
Primary completion1 Aug 2025
Study completion1 Sep 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for PTSDStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Participants (52 total) will be randomized, 26 to each of 2 arms one of which has 8 weekly PE sessions in early morning (between 07:00-10:00) and the other 8 sessions PE at 16:00 or later. Homework exposures will occur at the same time of day as PE. Primary outcomes measured at beginning, middle and end of treatment will be psychophysiological reactivity to trauma recall (mechanistic outcome) and CAPS-5 (clinical outcome). Secondary mechanistic outcome is peak SUDS during PE and clinical is PCL-5 measured at each PE session. Endogenous salivary cortisol levels will be tested as a mechanism of circadian effect. Data will be analyzed using multilevel, mixed-effects models.
Masking: Double blind
Who is masked: Care provider, Outcomes assessor
Enrolment: 52 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05453162
Sponsor's protocol ID: 2021p003356
Other IDs: R21MH128619
Status last verified: May 2026
First submitted: 29 Jun 2022
Last updated: 18 May 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: We will share data every January 15 and July 15 with the NIMH Data Archives (NDA) under a NIMH Data Repositories Data Submission Agreement between NIMH and VA Boston Health System (VABHS). Data sharing is required for all NIMH-funded research projects. The NDA DSA will be approved by the VABHS IRB. Each participant will be assigned Global Unique ID (GUID) and data shared will contain no identifiable information. Shared data will include scored psychophysiological, self-report instruments, cortisol, actigraphy, and fully de-identified demographic data.

Publications

Pace-Schott EF, Spencer RM, Vijayakumar S, Ahmed NA, Verga PW, Orr SP, Pitman RK, Milad MR. Extinction of conditioned fear is better learned and recalled in the morning than in the evening. J Psychiatr Res. 2013 Nov;47(11):1776-84. doi: 10.1016/j.jpsychires.2013.07.027. Epub 2013 Aug 28.
PubMed 23992769
Pace-Schott EF, Germain A, Milad MR. Effects of sleep on memory for conditioned fear and fear extinction. Psychol Bull. 2015 Jul;141(4):835-57. doi: 10.1037/bul0000014. Epub 2015 Apr 20.
PubMed 25894546
Meuret AE, Rosenfield D, Bhaskara L, Auchus R, Liberzon I, Ritz T, Abelson JL. Timing matters: Endogenous cortisol mediates benefits from early-day psychotherapy. Psychoneuroendocrinology. 2016 Dec;74:197-202. doi: 10.1016/j.psyneuen.2016.09.008. Epub 2016 Sep 15.
PubMed 27664810
Pace-Schott EF, Germain A, Milad MR. Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory. Biol Mood Anxiety Disord. 2015 May 29;5:3. doi: 10.1186/s13587-015-0018-9. eCollection 2015.
PubMed 26034578
Meuret AE, Trueba AF, Abelson JL, Liberzon I, Auchus R, Bhaskara L, Ritz T, Rosenfield D. High cortisol awakening response and cortisol levels moderate exposure-based psychotherapy success. Psychoneuroendocrinology. 2015 Jan;51:331-40. doi: 10.1016/j.psyneuen.2014.10.008. Epub 2014 Oct 16.
PubMed 25462905
Brueckner AH, Lass-Hennemann J, Wilhelm FH, Ferreira de Sa DS, Michael T. Cortisol administration after extinction in a fear-conditioning paradigm with traumatic film clips prevents return of fear. Transl Psychiatry. 2019 Apr 8;9(1):128. doi: 10.1038/s41398-019-0455-0.
PubMed 30962423

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All PTSD trials

Study at a glance

From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Circadian Influence on Fear Extinction Resulting From Prolonged Exposure Therapy for PTSD
ClinicalTrials.gov ID: NCT05453162
Acronym / sponsor ID: 2021p003356
Conditions: PTSD
Keywords: PTSD, Circadian, Exposure Therapy, Sleep, Cortisol
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 52 participants (estimated)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Collaborators: VA Boston Healthcare System, National Institute of Mental Health (NIMH)
Study start: 1 Jul 2022 (actual)
Primary completion: 1 Aug 2025 (actual)
Study completion: 1 Sep 2026 (estimated)
First posted: 12 Jul 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (care provider, outcomes assessor)
Number of arms: 2
Model description: Participants (52 total) will be randomized, 26 to each of 2 arms one of which has 8 weekly PE sessions in early morning (between 07:00-10:00) and the other 8 sessions PE at 16:00 or later. Homework exposures will occur at the same time of day as PE. Primary outcomes measured at beginning, middle and end of treatment will be psychophysiological reactivity to trauma recall (mechanistic outcome) and CAPS-5 (clinical outcome). Secondary mechanistic outcome is peak SUDS during PE and clinical is PCL-5 measured at each PE session. Endogenous salivary cortisol levels will be tested as a mechanism of circadian effect. Data will be analyzed using multilevel, mixed-effects models.

Arm	Type	Receives
Early morning PE	Experimental	Behavioral: Prolonged Exposure Therapy for Posttraumatic Stress Disorder26 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.
Late afternoon PE	Experimental	Behavioral: Prolonged Exposure Therapy for Posttraumatic Stress Disorder26 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

a diagnosis of PTSD as defined by DSM-5, with a minimum CAPS severity score of 26, a minimum PCL-5 score of 31, or a score of 2 or above on CAPS-5 Item B2 (concerning distressing dreams)
interest in starting a course of PE
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
Age range of 18-70
A Morningness-Eveningness Questionnaire (MEQ) score above 25.

Key exclusion criteria (15 listed)

current or past history of bipolar I disorder, schizophrenic or other psychotic disorders,
current organic brain disorder including moderate to severe traumatic brain injury
factitious disorder or malingering
pregnant or planning to become pregnant in the next four months at time of screening [if a participant does become pregnant during study procedures, the situation will be reviewed on a case-by-case basis and the participant's wishes will be considered in deciding whether the participant will continue with the study or withdraw.]
current moderate or severe substance use disorder with symptoms present within the past three months

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Prolonged Exposure Therapy for Posttraumatic Stress DisorderManualized procedures deliver ten 90-minute sessions targeted to occur weekly and administered via tele-health with the same study therapist. Session 1 will focus on psychoeducation. Session 2 involves construction of the in vivo exposure hierarchy. Sessions 3-10 focus on in-session imaginal exposures to the worst trauma memory for 45-60 min followed by 15-20 min of processing the imaginal exposure. For homework, participants will be instructed to confront situations on their hierarchy on a daily basis using recording of their imaginal exposure. Subjective Units of Distress (SUDS) ratings will be taken throughout imaginal exposure exercises.	Behavioural	Early morning PE, Late afternoon PE

Primary outcome

Psychophysiological reactivity to script-driven imagery (SDI-PR): Primary Mechanistic Outcome
Time frame: Between days -7 to -1, Baseline
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Between days 29-34, mid-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.
CAPS-5: Primary Clinical Outcome
Time frame: 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.

18 secondary outcomes

Subjective Units of Distress (SUDS): Secondary Mechanistic Outcome
Time frame: Day 14 Peak SUDS during PE therapy session 3
SUDS: Secondary Mechanistic Outcome
Time frame: Day 21 Peak SUDS during PE therapy session 4
SUDS: Secondary Mechanistic Outcome
Time frame: Day 28 Peak SUDS during PE therapy session 5
SUDS: Secondary Mechanistic Outcome
Time frame: Day 35 Peak SUDS during PE therapy session 6
SUDS: Secondary Mechanistic Outcome
Time frame: Day 42 Peak SUDS during PE therapy session 7
SUDS: Secondary Mechanistic Outcome
Time frame: Day 49 Peak SUDS during PE therapy session 8
SUDS: Secondary Mechanistic Outcome
Time frame: Day 56 Peak SUDS during PE therapy session 9
SUDS: Secondary Mechanistic Outcome
Time frame: Day 63 Peak SUDS during PE therapy session 10
PCL-5: PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition: Secondary Clinical Outcome
Time frame: Day 0 PCL-5 score at PE therapy session 1
PCL-5: Secondary Clinical Outcome
Time frame: Day 7 PCL-5 score at PE therapy session 2
PCL-5: Secondary Clinical Outcome
Time frame: Day 14 PCL-5 score at PE therapy session 3
PCL-5: Secondary Clinical Outcome
Time frame: Day 21 PCL-5 score at PE therapy session 4
PCL-5: Secondary Clinical Outcome
Time frame: Day 28 PCL-5 score at PE therapy session 5
PCL-5: Secondary Clinical Outcome
Time frame: Day 35 PCL-5 score at PE therapy session 6
PCL-5: Secondary Clinical Outcome
Time frame: Day 42 PCL-5 score at PE therapy session 7
PCL-5: Secondary Clinical Outcome
Time frame: Day 49 PCL-5 score at PE therapy session 8
PCL-5: Secondary Clinical Outcome
Time frame: Day 56 PCL-5 score at PE therapy session 9
PCL-5: Secondary Clinical Outcome
Time frame: Day 63 PCL-5 score at PE therapy session 10

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2026.
Background: PubMed 23992769Pace-Schott EF, Spencer RM, Vijayakumar S, Ahmed NA, Verga PW, Orr SP, Pitman RK, Milad MR. Extinction of conditioned fear is better learned and recalled in the morning than in the evening. J Psychiatr Res. 2013 Nov;47(11):1776-84. doi: 10.1016/j.jpsychires.2013.07.027. Epub 2013 Aug 28.
Background: PubMed 25894546Pace-Schott EF, Germain A, Milad MR. Effects of sleep on memory for conditioned fear and fear extinction. Psychol Bull. 2015 Jul;141(4):835-57. doi: 10.1037/bul0000014. Epub 2015 Apr 20.
Background: PubMed 27664810Meuret AE, Rosenfield D, Bhaskara L, Auchus R, Liberzon I, Ritz T, Abelson JL. Timing matters: Endogenous cortisol mediates benefits from early-day psychotherapy. Psychoneuroendocrinology. 2016 Dec;74:197-202. doi: 10.1016/j.psyneuen.2016.09.008. Epub 2016 Sep 15.
Background: PubMed 26034578Pace-Schott EF, Germain A, Milad MR. Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory. Biol Mood Anxiety Disord. 2015 May 29;5:3. doi: 10.1186/s13587-015-0018-9. eCollection 2015.
Background: PubMed 25462905Meuret AE, Trueba AF, Abelson JL, Liberzon I, Auchus R, Bhaskara L, Ritz T, Rosenfield D. High cortisol awakening response and cortisol levels moderate exposure-based psychotherapy success. Psychoneuroendocrinology. 2015 Jan;51:331-40. doi: 10.1016/j.psyneuen.2014.10.008. Epub 2014 Oct 16.
Background: PubMed 30962423Brueckner AH, Lass-Hennemann J, Wilhelm FH, Ferreira de Sa DS, Michael T. Cortisol administration after extinction in a fear-conditioning paradigm with traumatic film clips prevents return of fear. Transl Psychiatry. 2019 Apr 8;9(1):128. doi: 10.1038/s41398-019-0455-0.
Individual participant dataSharing planned: Yes. We will share data every January 15 and July 15 with the NIMH Data Archives (NDA) under a NIMH Data Repositories Data Submission Agreement between NIMH and VA Boston Health System (VABHS). Data sharing is required for all NIMH-funded research projects. The NDA DSA will be approved by the VABHS IRB. Each participant will be assigned Global Unique ID (GUID) and data shared will contain no identifiable information. Shared data will include scored psychophysiological, self-report instruments, cortisol, actigraphy, and fully de-identified demographic data.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Edward F Pace-Schott, PhD principal investigator

Massachusetts General Hospital

Suzanne L Pineles, PhD principal investigator

VA Boston Health System, Boston University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Prolonged Exposure Therapy for Posttraumatic Stress Disorder in people with PTSD, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Psychophysiological reactivity to script-driven imagery (SDI-PR): Primary Mechanistic Outcome (time frame: Between days -7 to -1, Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05453162, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2026.