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CompletedNCT01031979Updated Feb 7, 2018Results posted

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

A Phase 2 interventional study of Yohimbine and Placebo in Post-Traumatic Stress Disorder, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to male participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2018-02-07.

Sponsored by VA Office of Research and Development · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
26
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Post-Traumatic Stress Disorder

Keywords

  • PTSD
  • Prolonged Exposure
  • extinction
  • habituation
  • psychophysiology
03

In context

Stress Disorders, Post-Traumatic

2,284 studies on the registry are indexed under Stress Disorders, Post-Traumatic; 557 are open to participants now.

This study's enrollment of 26 is below the median of 70 across 1,897 interventional studies indexed under Stress Disorders, Post-Traumatic.

Browse Stress Disorders, Post-Traumatic studies →

Lead sponsor

VA Office of Research and Development is the lead sponsor of 1,767 studies on the registry; 394 are open to participants now.

Of its 209 completed or terminated interventional studies of FDA-regulated products, 183 (88%) have results posted.

Browse VA Office of Research and Development studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Male
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Yohimbime Group

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

    Drug: Yohimbine

  • Placebo comparator
    Placebo Group

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

    Drug: Placebo

Interventions

  • DrugYohimbine

    alpha-2 adrenergic receptor antagonist

  • DrugPlacebo

    Placebo

06

What researchers measure

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.

    Time frame: One week after drug visit

Secondary outcomes

  1. Change in Clinician Administered PTSD Scale (CAPS) Score

    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.

    Time frame: 0 Weeks, 15 weeks

  2. Change in Post Traumatic Stress Disorder Checklist (PCL) Score

    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.

    Time frame: 0 weeks, 15 weeks

  3. Change in Becks Depression Inventory (BDI-II) Score

    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.

    Time frame: 0 weeks, 15 weeks

07

Results

Posted Feb 24, 2017

Participant flow

Participant flow — Overall Study
MilestoneYohimbime GroupPlacebo Group
Started1412
Completed primary outcome measure1212
Completed98
Not completed54
Withdrew: Lost to follow-up54

Outcome measures

PrimaryTrauma-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.

Time frame:
One week after drug visit
Reported as:
Mean · beats per minute
Trauma-Cued Heart Rate Reactivity
beats per minuteYohimbine GroupPlacebo Group
Trauma-Cued Heart Rate Reactivity71.01 ± 3.8475.08 ± 3.11
Statistical analysis
  • Yohimbine Group vs Placebo Group · mixed effects/hierarchical linear model · p = <0.001 · Beta: -1.44 · 95% CI -2.29 to -0.59
SecondaryChange in Clinician Administered PTSD Scale (CAPS) Score

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.

Time frame:
0 Weeks, 15 weeks
Reported as:
Mean · units on a scale
Change in Clinician Administered PTSD Scale (CAPS) Score
units on a scaleYohimbine GroupPlacebo Group
Baseline CAPS67.33 ± 24.4965.00 ± 13.01
Week 15 CAPS (post-treatment)25.13 ± 14.9320.62 ± 10.84
Statistical analysis
  • Yohimbine Group vs Placebo Group · Hierarchical Linear Modeling · p = .39 · Slope: -0.87
SecondaryChange in Post Traumatic Stress Disorder Checklist (PCL) Score

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.

Time frame:
0 weeks, 15 weeks
Reported as:
Mean · units on a scale
Change in Post Traumatic Stress Disorder Checklist (PCL) Score
units on a scaleYohimbine GroupPlacebo Group
Baseline PCL64.00 ± 12.4960.25 ± 14.53
Week 15 PCL (post-treatment)27.37 ± 6.6328.50 ± 8.88
Statistical analysis
  • Yohimbine Group vs Placebo Group · Hierarchical Linear Modeling · p = .58 · Slope: -0.55
SecondaryChange in Becks Depression Inventory (BDI-II) Score

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.

Time frame:
0 weeks, 15 weeks
Reported as:
Mean · units on a scale
Change in Becks Depression Inventory (BDI-II) Score
units on a scaleYohimbine GroupPlacebo Group
Baseline BDI-II30.56 ± 13.1022.62 ± 7.05
Week 15 BDI-II (post-treatment)7.00 ± 5.687.87 ± 7.97
Statistical analysis
  • Yohimbine Group vs Placebo Group · Hierarchical Linear Modeling · p = .03 · Beta: -1.60 · 95% CI -2.71 to -0.49

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Yohimbine Group—0/12 (0%)0/12 (0%)
Placebo Group—0/12 (0%)0/12 (0%)

Baseline characteristics

14 participants were randomized to the yohimbine group; however only 12 completed the primary outcome assessment at session 4 and were able to be analyzed.

Age, Categorical
Age, Categorical(Participants)Yohimbine GroupPlacebo GroupTotal
<=18 years000
Between 18 and 65 years121224
>=65 years000
Age, Continuous
Age, Continuous(years)Yohimbine GroupPlacebo GroupTotal
Mean34.6 (18 to 45)29.9 (18 to 45)32.4 (18 to 45)
Sex: Female, Male
Sex: Female, Male(Participants)Yohimbine GroupPlacebo GroupTotal
Female000
Male121224
Region of Enrollment
Region of Enrollment(participants)Yohimbine GroupPlacebo GroupTotal
United States121224
08

Study locations

1 site
  • Ralph H. Johnson VA Medical Center, Charleston, SC
    Charleston, South Carolina 29401-5799, United States
09

References and documents

Publications

  • 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. PubMed 26654474 ↗
  • 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. PubMed 25809565 ↗

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Dec 2010 to primary completion in Apr 2015, 52 months.

Results were first posted in Feb 2017, 1 year 10 months after primary completion.

Of 85 non-industry phase 2 interventional studies under Stress Disorders, Post-Traumatic, half reached primary completion within 49 months of starting (the median), counting those still running; a quarter within 36 and three quarters within 59. This study's 52 months is close to that.

Counting every sponsor, half of 115 studies reached it within 41 months; a quarter within 23 and three quarters within 54.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 4, 2009
First posted
Dec 15, 2009
StartActual
Dec 1, 2010
Primary completionActual
Apr 1, 2015
CompletionActual
Jul 7, 2015
Results first posted
Feb 24, 2017
Last update
Feb 7, 2018
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 7, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01031979
Lead sponsor
VA Office of Research and Development
Responsible party
Sponsor
First posted
Dec 15, 2009
Start date
Dec 1, 2010
Primary completion
Apr 1, 2015
Completion
Jul 7, 2015
Results posted
Feb 24, 2017
Last update
Feb 7, 2018

Study contacts

Peter W. Tuerk, PhD MA BA
principal investigator · Ralph H. Johnson VA Medical Center, Charleston, SC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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