Prolonged Exposure for Post Traumatic Stress Disorder (PTSD) With/Without Yohimbine

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01031979
First received: December 4, 2009
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

The proposed study has three distinct but related research objectives. The first goal is to measure physiological correlates of successful treatment with Prolonged Exposure (PE) therapy for posttraumatic stress disorder (PTSD) in veterans of the Iraq and Afghanistan wars. Individuals with PTSD often experience elevated heart rates and other objectively measurable signs of anxiety when confronted with safe situations that remind them of past dangerous situations. We will measure physiological responses and compare the outcomes to patient's self reported subjective accounts of symptom improvement on traditional measures of PTSD. Developing a way to measure objective gains in symptoms improvement may help researchers who are studying ways to improve PTSD treatment. The second goal of the study is to investigate if yohimbine, a drug found to promote a specific type of learning, will improve treatment outcomes for veterans in PTSD treatment. The third goal is to investigate if ability to get used to loud startling audio tones correlates to baseline PTSD pathology and treatment outcomes for PE. This goal represents an important step forward in understanding characteristics of heritable traits that are related PTSD. It is significant because such research may one day lead to the development of individual responder policies that will assist patients by individualizing treatment plans based on personal characteristics.


Condition Intervention Phase
Post-Traumatic Stress Disorder
Drug: Yohimbine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Psychophysiology of Prolonged Exposure for PTSD With/Without Yohimbine

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Clinician Administered PTSD Scale [ Time Frame: 0 Weeks, 15 weeks, 27 weeks. ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: December 2010
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Patients will take one 21.6 mg. dose of yohimbine one hour before first imaginal exposure in PE.
Drug: Yohimbine
alpha-2 adrenergic receptor antagonist
Placebo Comparator: Arm 2
Patients will take a placebo one hour before first imaginal exposure in PE.
Drug: Placebo
Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be competent to provide informed consent for research participation.
  • Subjects must be male veterans and post deployed active duty male personnel of OEF/OIF.
  • Subjects must be between the ages of 18 and 45.
  • Subjects must meet DSM-IV diagnostic criteria for PTSD on the CAPS.
  • For subjects taking SSRI's, subjects must be stabilized on the current prescribed dose for a period of at least 14 days prior to the trial and remain at that dose for the remainder of the study. Subjects who change their SSRI status or dosage during the study will continue to receive services via the study resources but data generated will not be used in analyses. Subjects will be eligible for the study if they are willing to titrate off potentially confounding agents prior to yohimbine administration (for a period of five half-lives), given that such titration is also clinically appropriate and deemed to be in the patient's best interests.

Exclusion Criteria:

  • Subjects with a recent (< 2 month) history of psychiatric hospitalization or suicide attempt. Recent work with veterans with severe mental illness suggests that a 2-month period of stabilization is sufficient to minimize risk and possible relapse (Frueh, 2005). Subjects with an existing diagnosis of schizophrenia or other Axis I serious mental illnesses (SMI, besides PTSD) will be excluded. SMI will include any severe and persistent mental illness.
  • Subjects with a current diagnosis of drug dependence, due to potential interactions with study measurements and treatments. Alcohol use disorders will be allowed given that subjects can pass exclusion criterion 12 without withdrawal symptoms.
  • Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation.
  • Subjects with evidence of or a history of clinically significant hematological, endocrine, cardiovascular, hepatic, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect physiological/subjective responses.
  • Subjects with SCID-diagnosed panic disorder, as yohimbine may precipitate panic attacks.
  • Subjects with an abnormal ECG.
  • Subjects with a blood pressure of 140/90 or higher, as yohimbine has been shown to elevate blood pressure.
  • Subjects taking Beta blockers, alpha-adrenergic agents, Beta-agonist inhalers, opiates or opiate antagonists and any psychotropic medications other than SSRI's because these may affect test response.
  • Subjects who are unwilling or unable to maintain abstinence for three days prior to yohimbine administration from over-the-counter drugs with sympathomimetic properties, e.g., asthma medications, cold medicines with ephedrine, dietary supplements with ephedrine alkaloids, and illegal drugs, e.g., amphetamines, methamphetamine, cocaine, and MNDA as well as alcohol because these may exacerbate the action of yohimbine.
  • Subjects taking alpha-adrenergic antagonists, e.g. prazosin for hypertension; and beta-adrenergic antagonists, e.g. propranolol. Because they may attenuate effects of yohimbine. Subjects will be eligible for the study if they are willing to titrate off potentially confounding agents prior to yohimbine administration (for a period of five half-lives), given that such titration is also clinically appropriate and deemed to be in the patient's best interests.
  • Asthmatic subjects and subjects on medications for hypertension, due to criteria 9 and 10.

These inclusion/exclusion criteria will allow the majority of veterans treated in the PCT to be study eligible. Accordingly, the sample will be likely generalizable to the population of interest.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01031979

Contacts
Contact: Peter W Tuerk, BA MA PhD (843) 789-6188 ext 6188 Peter.Tuerk@va.gov
Contact: Bridgette K Niepoth, MA BS (843) 789-6652 bridgette.niepoth@va.gov

Locations
United States, South Carolina
Ralph H Johhnson VA Medical Center Recruiting
Charleston, South Carolina, United States, 29401-5799
Contact: Peter W Tuerk, BA MA PhD    843-789-6188 ext 6188    Peter.Tuerk@va.gov   
Principal Investigator: Peter W. Tuerk, BA MA PhD         
Sponsors and Collaborators
Investigators
Principal Investigator: Peter W. Tuerk, BA MA PhD Ralph H Johhnson VA Medical Center
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01031979     History of Changes
Other Study ID Numbers: CDA-2-013-09F
Study First Received: December 4, 2009
Last Updated: February 5, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
PTSD
Prolonged Exposure
extinction
habituation
psychophysiology

Additional relevant MeSH terms:
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Yohimbine
Adrenergic Antagonists
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014