Clinical trial NCT00475241: Exposure Therapy for Chronic PTSD: Efficacy and Mechanisms
Official title: Exposure Therapy for Chronic PTSD: Efficacy and Mechanisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Combat Disorders
Posttraumatic Stress Disorder
Keywords: Combat Disorders
Cortisol
Posttraumatic Stress Disorder (PTSD)
Psychophysiology
Therapy
Treatment
Veterans
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2007-05-21
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prolonged Exposure and Present Centered Therapy
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinician Administered PTSD Scale (Pre & Posttreatment)
timeFrame: PostTreatment (Week 12)
Secondary outcomes:
measure: Trauma Potentiated Startle
timeFrame: PostTreatment (Week 12)
measure: Cortisol Response to Awakening
timeFrame: PostTreatment (Week 12)
measure: Posttraumatic Cognitions Inventory
timeFrame: PostTreatment (Week 12)
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
Study officials:
affiliation: VA Ann Arbor Healthcare System
name: Sheila Rauch, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sripada RK, Rauch SA, Tuerk PW, Smith E, Defever AM, Mayer RA, Messina M, Venners M. Mild traumatic brain injury and treatment response in prolonged exposure for PTSD. J Trauma Stress. 2013 Jun;26(3):369-75. doi: 10.1002/jts.21813. Epub 2013 May 20.
citation: Sivakumar RK, Samy W, Pakpirom J, Songthamwat B, Karmakar MK. Ultrasound-guided selective trunk block: Evaluation of ipsilateral sensorimotor block dynamics, hemidiaphragmatic function and efficacy for upper extremity surgery. A single-centre cohort study. Eur J Anaesthesiol. 2022 Oct 1;39(10):801-809. doi: 10.1097/EJA.0000000000001736. Epub 2022 Aug 11.
citation: Rauch SAM, King AP, Liberzon I, Sripada RK. Changes in Salivary Cortisol During Psychotherapy for Posttraumatic Stress Disorder: A Pilot Study in 30 Veterans. J Clin Psychiatry. 2017 May;78(5):599-603. doi: 10.4088/JCP.15m10596.