Prolonged Exposure for Post Traumatic Stress Disorder (PTSD) With/Without Yohimbine
|ClinicalTrials.gov Identifier: NCT01031979|
Recruitment Status : Completed
First Posted : December 15, 2009
Results First Posted : February 24, 2017
Last Update Posted : February 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Post-Traumatic Stress Disorder||Drug: Yohimbine Drug: Placebo||Phase 2|
The proposed study has three distinct but related research objectives. The first research goal is to measure psychophysiological correlates of treatment gains associated with Prolonged Exposure (PE) therapy for PTSD in veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). Specifically, heart rate, heart rate variability, skin conductance, and facial electromyography, will be recorded before and after treatment during a three minute anxiety probe specific to the patient's index trauma. These measures will be compared to patient's self reported subjective accounts of symptom improvement on traditional measures of PTSD pathology (Subjective Units of Distress (SUDs), PTSD Checklist-Military Version (PCL), Clinician Administered PTSD Scale (CAPS), and the Beck Depression Inventory (BDI)). This goal is significant for veterans because currently no widely used objective criteria exist to measure treatment progress in PTSD. While the preponderance of existing evidence suggests that no one objective psychophysiological measurement will be a valid correlate for all individuals, even establishing a measurement paradigm that can show mean differences between groups will provide researchers with an objective tool to measure outcomes on clinical trials.
The second goal of the study is to investigate if the administration of yohimbine, a drug found to promote the extinction of conditioned fear in animal models, and more recently, in humans with claustrophobia, improves the facilitation of fear extinction in PE. Yohimbine is a safe drug that is already extensively used in human populations. Specifically, this goal will be investigated using a double blind placebo controlled randomized trial design. The hypothesis is that one 21mg oral dose of yohimbine given concurrently with a 40 minute imaginal exposure exercise in PE will lead to a greater reduction in cue-induced anxiety during the following weekly PE session than placebo. This goal is significant because current projections of PTSD in OEF/OIF veterans indicate that the need for psychological services will likely outpace the supply of such services. Accordingly, assisting treatments to be more efficient will likely translate into more veterans receiving much needed mental health services.
The 3rd goal is to investigate if ability to habituate to loud, 95db, audio tones correlates to baseline PTSD pathology and treatment outcomes for PE. This goal represents an important step forward in understanding characteristics of trait habituation, fear extinction, and learning in humans, which are all factors related to the successful treatment of PTSD. It is also significant because such research may lead to the development of individual responder policies that will assist veterans by individualizing treatment plans based on personal characteristics.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Psychophysiology of Prolonged Exposure for PTSD With/Without Yohimbine|
|Actual Study Start Date :||December 1, 2010|
|Actual Primary Completion Date :||April 1, 2015|
|Actual Study Completion Date :||July 7, 2015|
Experimental: Yohimbime Group
Patients will take one 21.6 mg. dose of yohimbine one hour before first imaginal exposure in PE.
alpha-2 adrenergic receptor antagonist
Placebo Comparator: Placebo Group
Patients will take a placebo one hour before first imaginal exposure in PE.
- Trauma-Cued Heart Rate Reactivity [ Time Frame: One week after drug visit ]The primary outcome was trauma-cued heart rate reactivity a week after the drug visit as measured by the PTSD Brief Reactivity (PBR) task. For each patient, a 3-minute trauma script was constructed containing vivid details of the target trauma and used in tandem with a standard neutral script for baseline measurement. Heart rate reactivity for each time point was the beats per minute (BPM) difference between the neutral and trauma scripts represented as a slope.
- Change in Clinician Administered PTSD Scale (CAPS) Score [ Time Frame: 0 Weeks, 15 weeks ]The CAPS is a structured interview for diagnosis of PTSD and is widely considered the gold-standard assessment. The CAPS produces a total score ranging from 0-136, with higher scores indicating more severe PTSD symptom severity. A 15-point decrease is considered clinically significant.
- Change in Post Traumatic Stress Disorder Checklist (PCL) Score [ Time Frame: 0 weeks, 15 weeks ]The PCL is a 17-item self-report measure of PTSD symptom severity based on the DSM-IV and has adequate psychometric properties. The PCL produces a score range between 17-85, with higher scores indicating more distress related to PTSD symptoms. A 10-point decrease on the PCL is considered clinically significant.
- Change in Becks Depression Inventory (BDI-II) Score [ Time Frame: 0 weeks, 15 weeks ]The BDI-II is a 21-item self-report measure that assesses depressive behavioral symptoms. It has demonstrated adequate psychometric validity, and external validity and is used widely as the dependent variable in treatment outcomes research. The BDI-II produces score ranges from 0-63, with higher scores indicating more severe depression symptom severity. A 5-point decrease on the BDI-II is considered clinically significant.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01031979
|United States, South Carolina|
|Ralph H. Johnson VA Medical Center, Charleston, SC|
|Charleston, South Carolina, United States, 29401-5799|
|Principal Investigator:||Peter W. Tuerk, PhD MA BA||Ralph H. Johnson VA Medical Center, Charleston, SC|