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Exposure Therapy for Chronic PTSD: Efficacy and Mechanisms

Exposure Therapy for Chronic PTSD: Efficacy and Mechanisms

Status
Completed
Phases
Phase 2Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00475241
Enrollment
36
Registered
2007-05-21
Start date
2008-01-31
Completion date
2010-07-31
Last updated
2019-02-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Combat Disorders, Posttraumatic Stress Disorder

Keywords

Combat Disorders, Cortisol, Posttraumatic Stress Disorder (PTSD), Psychophysiology, Therapy, Treatment, Veterans

Brief summary

The goals of the proposed research are to produce preliminary evidence of PE with OEF/OIF veterans with PTSD and to examine cognitive, psychophysiological, and neuroendocrine mechanisms of change in PTSD treatment. In brief, 36 OEF/OIF veterans with chronic PTSD or PTSS of at least 3 months duration will be randomly assigned to 15 sessions of either PE or TAU (see below for descriptions of the interventions). All veterans will receive psychobiological assessments at pre treatment, mid treatment, post treatment, 3 months, and 6 months follow-up. Each of these assessments will cover in 2 sessions on separate days and will include interview and self-report of symptoms (i.e., PTSD, depression, and general anxiety severity), self-report of PTSD-related cognitions, psychophysiological (i.e., heart rate, skin conductance, respiration, and end-tidal CO2) assessment during neutral and trauma scripts, and assessment of salivary cortisol during neutral and trauma scripts. Also, on the morning prior to each laboratory assessment, patients will collect salivary cortisol at the moment of waking and 30 and 45 minutes post-walking. In addition to these assessments, patients assigned to PE will collect salivary cortisol during three imaginal exposure sessions (sessions 3, 9, and 15).

Detailed description

Effective treatments for PTSD are available, with exposure therapy (ET) programs, including Prolonged Exposure (PE), having the most empirical evidence for effectiveness (Rothbaum et al., 2000). However, among people receiving treatment for PTSD, many are not receiving psychotherapies with empirically proven efficacy. In one VA VISN, only 10% of PTSD specialist therapists reported using ET routinely (Rosen et al., 2004). They suggested that a lack of training and human resources to provide ET, as well as misconceptions about exposure therapy may drive the deficit. Training efforts would be substantially more cost-effective of the proven treatments could be delivered in group formats. Development and proof of efficacy of a group-based PE would provide far more veterans with access to a treatment that can truly foster recovery from the devastating impact of PTSD. This is a central goal of this proposal. Little is known about the mechanisms through which PE leads to recovery. Delineation of its mechanisms is a critical step towards the development of treatment refinements to improve effectiveness and efficiency of the treatment. We plan to examine the potential roles of cognitive, psychophysiologic and neuroendocrine factors in symptom improvement. The mechanistic component will provide preliminary data on interactions between cognitive change (increased sense of self-competence and control over negative outcomes), psychophysiological habituation (reduced reactivity to trauma related stimuli), and reduced neuroendocrine sensitivity (reduced hypothalamic-pituitary-adrenal (HPA) axis reactivity). We predict that cognitive change, psychophysiological habituation and reduced HPA reactivity will all be related to symptom improvement with effective treatment. Thirty-six OEF/OIF veterans with chronic PTSD of at least 3 months duration will be randomly assigned to 15 weeks of twice weekly PE-G or TAU. All veterans will receive psychobiological assessments at pre treatment, mid treatment, post treatment, 3 months and 6 months follow-up. Each of these assessments will include interview and self-report of symptoms (i.e., PTSD, depression, and general anxiety severity), self-report of PTSD-related cognitions, psychophysiological (i.e., heart rate, skin conductance, respiration, and end-tidal CO2) assessment during neutral and trauma scripts, and assessment of salivary cortisol during neutral and trauma scripts. Also, on the morning prior to each laboratory assessment, patients will collect salivary cortisol at the moment of waking and 30 and 45 minutes post-walking. The results from this study will be used as pilot data for VA Merit Award and NIMH R01 applications for larger follow-up studies.

Interventions

BEHAVIORALProlonged Exposure therapy for PTSD

exposure-based treatment for PTSD

present focused coping and problem solving for PTSD

Sponsors

VA Office of Research and Development
Lead SponsorFED

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)

Masking description

Blinded Assessors

Intervention model description

Prolonged Exposure and Present Centered Therapy

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* OEF/OIF Veterans with combat related posttraumatic stress disorder (PTSD) or posttraumatic stress symptoms (PTSS) of at least 3 months duration with significant impairment (PSSI greater than or equal to 15).

Exclusion criteria

* Any current level of personality disorder or suicidal risk that in the judgment of the investigator makes it unlikely or contraindicated that the patient can adhere to the study regimen. * Psychosis * Alcohol or substance dependence in the past 3 months * Working night-shifts * Changes to psychoactive medication in the past 8 weeks * Taking medication that makes HPA axis measures difficult to interpret

Design outcomes

Primary

MeasureTime frameDescription
Clinician Administered PTSD Scale (Pre & Posttreatment)PostTreatment (Week 12)Clinician Administered PTSD Scale (CAPS) assesses PTSD symptom severity. Scores range from 0 to 136 and higher scores represent more severe symptoms.

Secondary

MeasureTime frameDescription
Trauma Potentiated StartlePostTreatment (Week 12)Psychophysiological reactivity will be assessed using electromyography collected using a Biopac MP-100 physiology. The potentiation is recorded using a difference score (trauma probe response minus non-trauma probe response). The unit of measure is µV. Higher is more response to trauma cue compared to non-trauma cue.
Cortisol Response to AwakeningPostTreatment (Week 12)Area under the curve for awakening, 30 min, and 45 minute salivary cortisol assays. Higher means more cortisol response to awakening detected.
Posttraumatic Cognitions InventoryPostTreatment (Week 12)Self-report measure of trauma-related cognitions. Range is 21-147. Higher is more problematic trauma-related cognitions.

Countries

United States

Participant flow

Participants by arm

ArmCount
Prolonged Exposure
Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD
11
Present Centered Therapy
Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD
15
Total26

Baseline characteristics

CharacteristicProlonged ExposurePresent Centered TherapyTotal
Age, Continuous29.8 years
STANDARD_DEVIATION 6.5
32.9 years
STANDARD_DEVIATION 7.2
31.6 years
STANDARD_DEVIATION 7
CAPS79.2 units on a scale
STANDARD_DEVIATION 12.1
77.4 units on a scale
STANDARD_DEVIATION 12.1
78.2 units on a scale
STANDARD_DEVIATION 11.9
Region of Enrollment
United States
11 Participants15 Participants26 Participants
Sex: Female, Male
Female
2 Participants0 Participants2 Participants
Sex: Female, Male
Male
9 Participants15 Participants24 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 110 / 15
serious
Total, serious adverse events
0 / 110 / 15

Outcome results

Primary

Clinician Administered PTSD Scale (Pre & Posttreatment)

Clinician Administered PTSD Scale (CAPS) assesses PTSD symptom severity. Scores range from 0 to 136 and higher scores represent more severe symptoms.

Time frame: PostTreatment (Week 12)

Population: Treatment Completers

ArmMeasureValue (MEAN)Dispersion
Prolonged ExposureClinician Administered PTSD Scale (Pre & Posttreatment)30.0 units on a scaleStandard Deviation 18.4
Present Centered TherapyClinician Administered PTSD Scale (Pre & Posttreatment)53.6 units on a scaleStandard Deviation 28.7
Secondary

Cortisol Response to Awakening

Area under the curve for awakening, 30 min, and 45 minute salivary cortisol assays. Higher means more cortisol response to awakening detected.

Time frame: PostTreatment (Week 12)

Population: Patient assay quality not adequate for some patients

ArmMeasureValue (MEAN)Dispersion
Prolonged ExposureCortisol Response to Awakening1.2 min*mg/mLStandard Deviation 0.4
Present Centered TherapyCortisol Response to Awakening.5 min*mg/mLStandard Deviation 0.4
Secondary

Posttraumatic Cognitions Inventory

Self-report measure of trauma-related cognitions. Range is 21-147. Higher is more problematic trauma-related cognitions.

Time frame: PostTreatment (Week 12)

Population: patients with missing data not included

ArmMeasureValue (MEAN)Dispersion
Prolonged ExposurePosttraumatic Cognitions Inventory91.3 units on a scaleStandard Deviation 41.9
Present Centered TherapyPosttraumatic Cognitions Inventory97.1 units on a scaleStandard Deviation 45.6
Secondary

Trauma Potentiated Startle

Psychophysiological reactivity will be assessed using electromyography collected using a Biopac MP-100 physiology. The potentiation is recorded using a difference score (trauma probe response minus non-trauma probe response). The unit of measure is µV. Higher is more response to trauma cue compared to non-trauma cue.

Time frame: PostTreatment (Week 12)

Population: data was not available due to recording errors for some patients

ArmMeasureValue (MEAN)Dispersion
Prolonged ExposureTrauma Potentiated Startle4.8 µVStandard Deviation 16.2
Present Centered TherapyTrauma Potentiated Startle19.5 µVStandard Deviation 30.3

Source: ClinicalTrials.gov · Data processed: Feb 27, 2026