Exposure Therapy for Chronic PTSD: Efficacy and Mechanisms

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00475241
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2
• Duration (Months): 30
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Combat Disorders; Posttraumatic Stress Disorder	Behavioral: Prolonged Exposure therapy for PTSD; Behavioral: Present centered therapy for PTSD	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prolonged Exposure and Present Centered TherapyProlonged Exposure and Present Centered Therapy
• Masking: Single (Outcomes Assessor)
• Masking Description: Blinded Assessors
• Primary Purpose: Treatment
• Official Title: Exposure Therapy for Chronic PTSD: Efficacy and Mechanisms
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prolonged Exposure Therapy Prolonged exposure therapy for PTSD	Behavioral: Prolonged Exposure therapy for PTSD; exposure-based treatment for PTSD
Active Comparator: Present Centered Therapy Present centered therapy for PTSD	Behavioral: Present centered therapy for PTSD; present focused coping and problem solving for PTSD

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Trauma Potentiated Startle [PostTreatment (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.

2. Cortisol Response to Awakening [PostTreatment (Week 12)]

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

3. Posttraumatic Cognitions Inventory [PostTreatment (Week 12)]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Ann Arbor Healthcare System	Ann Arbor	Michigan	United States	48113

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Sheila Rauch, PhD, VA Ann Arbor Healthcare System

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT00475241
• Other Study ID Numbers: CDA-2-010-06F
• First Posted: May 21, 2007
• Last Update Posted: Feb 15, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by VA Office of Research and Development: Combat Disorders; Cortisol; Posttraumatic Stress Disorder (PTSD); Psychophysiology; Therapy; Treatment; Veterans
• Additional relevant MeSH terms: Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Combat Disorders

Study Results

Participant Flow

Arm/Group Title	Prolonged Exposure	Present Centered Therapy
Arm/Group Description	Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD	Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD
Period Title: Overall Study
STARTED	18	18
COMPLETED	11	15
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Prolonged Exposure	Present Centered Therapy	Total
Arm/Group Description	Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD	Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD	Total of all reporting groups
Overall Participants	11	15	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.8 (6.5)	32.9 (7.2)	31.6 (7.0)
Sex: Female, Male (Count of Participants)
Female	2 18.2%	0 0%	2 7.7%
Male	9 81.8%	15 100%	24 92.3%
Region of Enrollment (Count of Participants)
United States	11 100%	15 100%	26 100%
CAPS (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	79.2 (12.1)	77.4 (12.1)	78.2 (11.9)

Outcome Measures

1. Primary Outcome

Title	Clinician Administered PTSD Scale (Pre & Posttreatment)
Description	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)

Outcome Measure Data

Analysis Population Description

Treatment Completers

Arm/Group Title	Prolonged Exposure	Present Centered Therapy
Arm/Group Description	Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD	Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD
Measure Participants	11	15
Mean (Standard Deviation) [units on a scale]	30.0 (18.4)	53.6 (28.7)

2. Secondary Outcome

Title	Trauma Potentiated Startle
Description	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)

Outcome Measure Data

Analysis Population Description

data was not available due to recording errors for some patients

Arm/Group Title	Prolonged Exposure Therapy	Present Centered Therapy
Arm/Group Description	Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD	Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD
Measure Participants	7	10
Mean (Standard Deviation) [µV]	4.8 (16.2)	19.5 (30.3)

3. Secondary Outcome

Title	Cortisol Response to Awakening
Description	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)

Outcome Measure Data

Analysis Population Description

Patient assay quality not adequate for some patients

Arm/Group Title	Prolonged Exposure	Present Centered Therapy
Arm/Group Description	Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD	Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD
Measure Participants	7	10
Mean (Standard Deviation) [min*mg/mL]	1.2 (.4)	.5 (.4)

4. Secondary Outcome

Title	Posttraumatic Cognitions Inventory
Description	Self-report measure of trauma-related cognitions. Range is 21-147. Higher is more problematic trauma-related cognitions.
Time Frame	PostTreatment (Week 12)

Outcome Measure Data

Analysis Population Description

patients with missing data not included

Arm/Group Title	Prolonged Exposure	Present Centered Therapy
Arm/Group Description	Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD	Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD
Measure Participants	11	14
Mean (Standard Deviation) [units on a scale]	91.3 (41.9)	97.1 (45.6)

Adverse Events

Arm/Group Title	Prolonged Exposure		Present Centered Therapy
Arm/Group Description	Prolonged exposure therapy for PTSD Prolonged Exposure therapy for PTSD: exposure-based treatment for PTSD		Present centered therapy for PTSD Present centered therapy for PTSD: present focused coping and problem solving for PTSD
All Cause Mortality
	Prolonged Exposure		Present Centered Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Prolonged Exposure		Present Centered Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Prolonged Exposure		Present Centered Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.