Noradrenergic Manipulation and Virtual Reality Exposure Therapy in Phobic Participants

July 6, 2015 updated by: Paul M.G.Emmelkamp, VU University of Amsterdam
Recent advances in animal research have identified pharmacological agents that appear to both accelerate and consolidate extinction learning. One cognitive enhancers is Yohimbine hydrochloride (YOH). A finding in animal literature is that the administration of YOH during extinction trials accelerates fear reduction and may convert ineffective exposures in to successful ones. It is thought that the mechanism of enhanced emotional memory is through elevated norepinephrine. However, recent findings demonstrate mixed results. In a randomized controlled trial claustrophobic participants underwent exposure in combination with YOH or placebo. The YOH group showed significantly better results on anxiety improvement than the placebo group. In a more recent study with participants with fear of flying no additional benefits of YOH were demonstrated. Therefore, we intend to replicate and extend these studies by enhancing the dose of YOH in combination with VRET and by extending our experimental design with another group which receives propranolol in combination with VRET. Propranolol is β-adrenergic receptor antagonist, which has proven to disrupt reconsolidation in healthy humans. In this randomized controlled trial a between groups design is chosen to further characterize the differential within and between trial extinction and to enhance possible between groups effects. Sixty participants with fear of flying or fear of heights will be randomly assigned to one of the following three conditions 1) VRET plus YOH, 2) VRET plus Propranolol, or 3) VRET plus placebo. Participants in all conditions will be offered three sessions of VRET over a period of two weeks.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Nord Holland
      • Amsterdam, Nord Holland, Netherlands, 1018XA
        • University of Amsterdam

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Marked fear of flying or acrophobia, indicated by a subjective fear rating of moderate or higher on anxiety specific measures.

Being older than 18 years and younger than 75 years.

Exclusion Criteria:

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: VRET plus Yohimbine
Virtual Reality Exposure Therapy combined with the administration of yohimbine.
Behavioral: Virtual Reality Exposure Therapy (VRET)
Graded exposure to feared specific stimulus by computer-generated 3D virtual environments.
Active Comparator: VRET plus propranolol
Virtual Reality Exposure Therapy combined with the administration of propranolol
Behavioral: Virtual Reality Exposure Therapy (VRET)
Graded exposure to feared specific stimulus by computer-generated 3D virtual environments.
Placebo Comparator: VRET plus placebo
Virtual Reality Exposure Therapy combined with the administration of a non-active placebo pill
Behavioral: Virtual Reality Exposure Therapy (VRET)
Graded exposure to feared specific stimulus by computer-generated 3D virtual environments.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
FAS (Flight Anxiety Situations Questionnaire)
Time Frame: Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The FAS is 32-item, self-report inventory designed to measure anxiety related to flying experienced in different situations. The FAS is divided into three subscales: the Anticipation scale, which represents situations before the actual flight, the In-flight scale, which refers to situations during a flight and the Generalized flight scale.
Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
AQ (Acrophobia Questionnaire)
Time Frame: Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The AQ (Cohen, 1977) is a 40-item self-report measure to assess anxiety in height situations. The AQ measures anxiety and avoidance behavior relative to height situations. Subject can express their fear on a scale ranging from 0-6, whereby 0 stands for "no fear at all" and 6 for "almost panic" (ranging from 0-120).
Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
WAQ (Weekly Anxiety Questionnaire)
Time Frame: In session 1, 2 and 3 and Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The WAQ is an author-constructed transdiagnostic anxiety questionnaire to rate severity of experienced general anxiety. The WAQ is a 10-item self-report measure on which participants can rate their experienced anxieties. Ratings can be scored on a five-point Likert scale ranging from "not at all" to "permanently".
In session 1, 2 and 3 and Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
FAM (Flight Anxiety Modalities Questionnaire)
Time Frame: Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The FAM is 23-item, self-report inventory designed to measure how fear of flying can be expressed. On a five-point-likert scale the intensity of fear can be rated. The FAM is divided into two subscales: the Somatic Modality, which represents the physical symptoms and the Cognitive Modality, which measures distressing cognitions.
Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
ATHQ (Attitude towards heights questionnaire)
Time Frame: Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The ATHQ contains six questions assessing the attitude towards heights (range 0-60).
Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
DASS (Depression Anxiety Stress Scale)
Time Frame: Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The DASS is 42-item self-report measure that assesses level of depression, anxiety, and stress over the previous week. Each scale consists of 14 items, which are grouped into smaller subscales. The depression scale consists of the following subscales: dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia and inertia. The anxiety scale consists of: autonomic arousal, skeletal musculature effects, situational anxiety and subjective experience of anxious affect. The stress scale consists of: difficulty relaxing, nervous arousal, easily agitated, irritable/overreactive and impatient. The internal consistency of the DASs is good to excellent (Cronbach's alpha ranging from .88 to .96; Brown et al., 1997).
Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
PIT (Prospective Imagery Task)
Time Frame: Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The PIT is based on MacLeod and Byrne, (1996) and Stöber, (2000) and will be used to measure imagery for 10 positive and 10 negative prospective events. As in Holmes, Lang, et al. (2008), subjects will be asked to rate the vividness of prospective positive events (e.g., "You will have lots of energy and enthusiasm") or negative events (e.g., "Someone close to you will reject you") on a 5-point scale (1 = no image at all; 5 = very vivid).
Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
ASI (Anxiety Sensitivity Inventory)
Time Frame: Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
The ASI is a 16-items self-report questionnaire, measuring fear of anxiety-related symptoms. Each item is rated on a five-point likert scale ranging from 0 (very little) to 4 (very much). The ASI is scored by summing all items; possible scores range from 0 to 64, with higher scores reflecting higher levels of anxiety sensitivity.
Pre- (baseline) and post-assessment (after treatment termination, within 3 weeks after first treatment session) and 3 month follow up (3 month after post assessment)
SUDs (Subjective Units of Discomfort)
Time Frame: Every 3 minutes during exposure (exposure will be done twicely 25 minutes every therapy session. Thus, starting at minute 1 every 3 minute a SUD will be asked. After a break of 10 minutes, exposure will start again (25 minutes).
Subjective Units of Discomfort (SUDs) will be taken every 3 minutes to monitor patients' subjective anxiety (Wolpe, 1990).
Every 3 minutes during exposure (exposure will be done twicely 25 minutes every therapy session. Thus, starting at minute 1 every 3 minute a SUD will be asked. After a break of 10 minutes, exposure will start again (25 minutes).

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
QMI (Questionnaire upon Mental Imagery)
Time Frame: Pre-assessment (baseline); first treatment session will follow within 3 weeks
The QMI measures vividness of imagery typically experienced by participants across seven sensory modalities: visual, auditory, cutaneous, gustatory, kinaesthetic, olfactory, and organic. The QMI is a reliable instrument containing 35 items. The items rate the vividness on a seven point scale (1 = "I perceive it perfectly clearly, as if it were real"; 7 = "I think about it, but I cannot imagine it").
Pre-assessment (baseline); first treatment session will follow within 3 weeks
IPQ (Igroup Presence Questionnaire)
Time Frame: Post session 1, 2 and 3 (all within 2 weeks, maximum 3 weeks)
The IPQ is a 14-item, self-report inventory designed to measure to what degree participants experience the virtual environments as real.The IPQ consists of three underlying factors, which refer to respectively: 1) the spatial presence, meaning which is the sense of really being in a virtual environment, 2) involvement: the attention which is paid to the real world and to the virtual environments and 3) the realness of the virtual world, which refers to the reality jugdement of the virtual world. The subject can give an indication of how real the virtual world is on a scale ranging from -3 to +3, respectively "completely disagree" and "completely agree".
Post session 1, 2 and 3 (all within 2 weeks, maximum 3 weeks)
SSQ (Simulator Sickness Questionnaire)
Time Frame: Post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
The SSQ is a 27-item self-report questionnaire designed to measure whether subjects experienced any physiological symptoms during and after being in the virtual environments. Participants can give an indication whether and to what degree they experienced twenty-seven physiological symptoms: with underlying factors tiredness, anxiety or panic and traumatic memory.
Post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
EEQ (Exposure Experience Questionnaire)
Time Frame: Post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
The EEQ is a 7-item author-constructed self-report questionnaire we designed to measure the degree of anxiety and presence after virtual reality exposure therapy.
Post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
TGAQ (Treatment Gain and Attribution Questionnaire)
Time Frame: Post-assessment (inmediately after the last treatment session)
The TGAQ is based on the TGAQ from Powers and colleague's and (Powers et al., 2008) is a fourteen-item scale assesses participants' perceptions of their level of improvement and the extent to which the herbal supplement facilitated or interfered with their exposure treatment. The four dimensions are rated using 100-point visual analogue scales, including the following: (a) overall improvement (not at all improved to much improved), (b) medication interference (not at all detrimental to extremely detrimental), (c) medication facilitation (not at all helpful to extremely helpful), and (d) exposure facilitation (not at all helpful to extremely helpful).
Post-assessment (inmediately after the last treatment session)
Drug guess
Time Frame: Post-assessment (inmediately after the last treatment session)
A questionnaire consisting of 5 questions concerning the medication and its possible effects will be used to assess whether participants are aware in which drug condition they participate. Participants are asked whether they had received YOH/propranolol or placebo and rated on a scale ranging from 0 (not sure at all) to 100 (definite) how sure they were that their guess was right.
Post-assessment (inmediately after the last treatment session)
Self-efficacy questionnaire
Time Frame: Pre- and post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
The self-efficacy questionnaire is a self-report inventory designed to measure the degree of self-efficacy subjects experienced with respect to the phobic situation. The inventory consists of five items on self-efficacy in phobic situations. The items represent five different themes 1) the capability to reduce the experienced fear, 2) to think clearly, 3) to control for ones own actions, 4) to control anxious thoughts and feelings and 5) to stay in the situation while experiencing intense fear. The participant can give an indication by giving a percentage representing their evaluation of their own capability.
Pre- and post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
Cognitions Questionnaire
Time Frame: Post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
The cognition questionnaire is a self-report inventory designed to investigate the level of positive and negative cognitions subjects have about themselves. The questionnaire consists of 30 items for fear of flying which can be scored on a five-point Likert scale ranging from "not at all" to "permanently".
Post session 1, 2 and 3 (all within 2 weeks with a maximum of 3 weeks)
Expectancy
Time Frame: Pre-assessment (baseline); first treatment session will follow within 3 weeks
Participants expectancy about the outcome will be rated on a 5-item self-report scale based on the Borkovec and Nau (1972) expectancy of improvement scale (0%-100%).
Pre-assessment (baseline); first treatment session will follow within 3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VU University of Amsterdam

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Paul Emmelkamp, PhD, University of Amsterdam

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 20, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 8, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2012-KP-2464

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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