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

NCT01031979 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CDA-2-013-09F
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Post-Traumatic Stress Disorder

Keywords

PTSD; Prolonged Exposure; extinction; habituation; psychophysiology

Outcome Measures

Primary Outcomes (1)

• Trauma-Cued Heart Rate Reactivity

  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.

  One week after drug visit

Secondary Outcomes (3)

• Change in Clinician Administered PTSD Scale (CAPS) Score

  0 Weeks, 15 weeks

• Change in Post Traumatic Stress Disorder Checklist (PCL) Score

  0 weeks, 15 weeks

• Change in Becks Depression Inventory (BDI-II) Score

  0 weeks, 15 weeks

Study Arms (2)

Yohimbime Group

EXPERIMENTAL

Patients will take one 21.6 mg. dose of yohimbine one hour before first imaginal exposure in PE.

Drug: Yohimbine

Placebo Group

PLACEBO COMPARATOR

Patients will take a placebo one hour before first imaginal exposure in PE.

Drug: Placebo

Interventions

Yohimbine DRUG

alpha-2 adrenergic receptor antagonist

Yohimbime Group

Placebo DRUG

Placebo

Placebo Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Males only.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5799, United States

Location

Related Publications (2)

• Keller SM, Tuerk PW. Evidence-based psychotherapy (EBP) non-initiation among veterans offered an EBP for posttraumatic stress disorder. Psychol Serv. 2016 Feb;13(1):42-8. doi: 10.1037/ser0000064. Epub 2015 Dec 14.

  PMID: 26654474 DERIVED

• Yuen EK, Gros DF, Price M, Zeigler S, Tuerk PW, Foa EB, Acierno R. Randomized Controlled Trial of Home-Based Telehealth Versus In-Person Prolonged Exposure for Combat-Related PTSD in Veterans: Preliminary Results. J Clin Psychol. 2015 Jun;71(6):500-12. doi: 10.1002/jclp.22168. Epub 2015 Mar 25.

  PMID: 25809565 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Substance-Related Disorders

Interventions

Yohimbine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Peter Tuerk
• Organization: Ralph H. Johnson VAMC

peter.tuerk@va.gov

(843) 789-6188

Study Officials

• Peter W. Tuerk, PhD MA BA

  Ralph H. Johnson VA Medical Center, Charleston, SC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2009
• First Posted: December 15, 2009
• Study Start: December 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: July 7, 2015
• Last Updated: February 7, 2018
• Results First Posted: February 24, 2017

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)