Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001661167
Ethics application status
Approved
Date submitted
2/09/2019
Date registered
27/11/2019
Date last updated
27/11/2019
Date data sharing statement initially provided
27/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Stress augmentation of exposure therapy: Mechanisms and implications for relapse
Scientific title
Effects of acute stress on the strength and durability of Extinction Learning: Implications for Exposure-based treatment and Relapse Prevention
Secondary ID [1] 299104 0
Nil known
Universal Trial Number (UTN)
U1111-1239-1812
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spider Phobia 314154 0
Specific Phobia 314155 0
Anxiety Disorders 314172 0
Condition category
Condition code
Mental Health 312524 312524 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Virtual Reality Exposure Therapy to spiders

2 individual, face-to-face weekly treatment sessions will be conducted using virtual reality (VR) goggles. The total duration of the intervention will be three weeks (including 2 exposure treatments, as well as pre- and post-assessment procedures). Follow-Up assessment will be conducted 3 months later. Exposure will involve a set of guided exposure tasks to VR spiders for approx. 1 hour each session. This will be administered individually by a trained psychologist. On the first treatment day, exposure tasks will include the observation of a virtual spider in a virtual kitchen and participants will be asked to approach the spider as closely as they can using their 3D wand to navigate through the virtual world. Participants will then be required to touch the virtual spider with their virtual hand and the spider will respond by fleeing (without tactile feedback). On the second treatment day (one week later), participants will be encouraged to pick a vase where an animated spider with wiggly legs will drift to the floor of the virtual kitchen. They will then be required to touch the virtual spider image with their cyberhand to explore the virtual spider. Simultaneously, their real hand will explore a toy spider attached in order to allow the spider to feel furry and more tangible (adapted from Hoffmans, 2002). SUDs (subjective units of distress) ratings will be reported every 30 seconds. SUDS < 30 will be the criterion used to define the completion of an exposure task. Participants will be instructed not to use cognitive avoidance strategies and this will be measured with several questions afterwards. Adherence to the treatment will be monitored via clinical observation and clinician's ratings of client's engagement, the severity of fear and avoidance.

Psychoeducative material about exposure therapy will be provided orally and using a handout designed specifically for this study. It will involve discussion of the purpose and benefits of exposure therapy, the role of avoidance and safety behaviours in maintaining anxiety/fear in the long term and the evidence for VR exposure treatment.

This condition will include a stress manipulation, the Socially Evaluated Cold Presser Task (SECPT) 20 minutes prior to exposure therapy. The SECPT is designed to elevate cortisol (stress hormone levels). It involves the immersion of one's dominant hand into a basin with ice-cold water (0-2 degrees Celsius) for 3 minutes whilst being recorded by a video camera and observed by a researcher. Participants will be instructed to submerge their hand including their wrist and they will not be informed of the duration of the SECPT.
Intervention code [1] 315369 0
Behaviour
Comparator / control treatment
The exposure-based treatment sessions for the control group will include all the same elements as the treatment (including psychoeducative material and exposure tasks in a kitchen context) in the equivalent order and the same timing. However, the stress procedure will be replaced with a control procedure. That is, participants will immerse their dominant hand into warm water (35-37 degrees Celsius) with no recording or experimenter present.
Control group
Active

Outcomes
Primary outcome [1] 321170 0
Change in the Behavioural Avoidance Test (BAT) with spiders using VR goggles

BAT involves short VR exposure task to a spider and calculating distance between VR spider and participant. VR context will differ between post- treatment and follow-up assessment. VR spider presented in a garden at post-treatment and in a Kitchen ( the treatment context) at follow-up.
Timepoint [1] 321170 0
1 time at pre-treatment (baseline), post- treatment( Week 3-primary endpoint 1) and follow-up assessment ( 12 weeks after final treatment session or 14 weeks post-enrolment-primary endpoint 2).

There are two primary endpoints in order to assess group differences in the return of fear following a change in context ( research question 1) and overtime ( research question 2)
Secondary outcome [1] 374155 0
Change in spider-fear-related symptoms

The Spider Phobia Questionnaire (Klorman et al., 1974) and Fear of Spider questionnaire (Symanski, 1995) will be employed
Timepoint [1] 374155 0
1 time at pre-treatment (baseline), post-treatment (Week 3) and follow-up-treatment (Week 14)
Secondary outcome [2] 374156 0
Free salivary Cortisol

This will be a marker of HPA axis activity and stress manipulation check (SECPT). Saliva will be collected using the Salivette sampling devices.
Timepoint [2] 374156 0
10 samples will be collected per participant.
Baseline saliva samples will be collected at pre-treatment (Week 1), post-treatment( Week 2) and follow-up assessment ( Week 14) immediately before the BAT. An additional baseline saliva sample will be taken in treatment session 2 ( Week 2), 5 min prior to the stress/control procedure.
In treatment session 1 and 2( Weeks 1 and 2), saliva samples will be collected 1, 20 and 35 min after the stress/control procedure.
Secondary outcome [3] 374189 0
Alpha Amylase activity

This will be collected using Salivette sampling devices. This will be a measure of central noradrenergic activation (Nater & Rohleder, 2009).
Timepoint [3] 374189 0
The same time points as the salivary cortisol samples will be used.
Secondary outcome [4] 374190 0
Skin Conductance Response

This data will be collected using a watch that measures Galvanic Skin Conductance
Timepoint [4] 374190 0
5 min before the BAT at pre-treatment ( baseline) and during the BAT at Pre-treatment (Week 1)
During VR treatment session 1 and 2 ( Week 1 and 2)
During the BAT at Post-treatment ( Week 3)
During the BAT a Follow-Up (Week 14)
Secondary outcome [5] 374191 0
Eye gaze responses

This will be obtained using a Virtual Reality headset that measures eye tracking as a measure of attention towards the spider.
Timepoint [5] 374191 0
During treatment sessions 1 and 2
Secondary outcome [6] 374192 0
Subjective US expectancy ratings

These ratings will assess the participants expectancy of harm by measuring their amount of anticipatory fear and the perceived likelihood their feared outcome will occur.
Timepoint [6] 374192 0
Immediately before and after the BAT at Pre-treatment (baseline- Week 1), Post-treatment( Week 3) and Follow-Up (Week 14).
At the start and end of each exposure task during VR treatment sessions ( Week 1 and 2).
Secondary outcome [7] 374193 0
DAS-21 (Lovibond & Lovibond, 1995)

This questionnaire will be used to measure the emotional states of depression, anxiety and stress
Timepoint [7] 374193 0
1 time shortly before the BAT at pre-treatment (baseline), post-treatment(Week 3) and follow-Up (Week 12).
Secondary outcome [8] 376756 0
Skin Conductance Response (SCR)

This data will be collected using the same watch that measures Galvanic Skin Conductance
Timepoint [8] 376756 0
The same time points used for SCR

Eligibility
Key inclusion criteria
Participants between the ages of 18 and 60 who diagnostic criteria for a specific phobia of spiders (DSM-V).
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Currently engaged in other active psychological or pharmacological treatment
- Comorbid disorder that is more primary or distressing
- Presence of serious or chronic medical illness
- Substance abuse problems
- Psychosis
- Pregnant and lactating

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The intake process which assesses for eligibility into the study will conducted by an external researcher who will not be involved in the treatment process or testing process.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subject will be randomly allocated to conditions using randomisation table created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
At the end of treatment, participants will be asked to explain what they believed the purpose of the water-based task was.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be entered blindly into SPSS software. Group differences in demographic and clinical characteristics will be analysed with one-way ANOVAs. Two-way repeated measures ANOVAs (with treatment group as the between-subject factor and time as the within-subject factor) will be used to determine the effect stress manipulation on cortisol concentrations and treatment outcomes. One-way ANOVAs and post-hoc t-tests will be used to analyse treatment effects at certain time points. A regression analysis will be used to test variables hypothesised to mediate the effects of stress on the primary treatment outcome.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/12/2019
Actual
Date of last participant enrolment
Anticipated
28/09/2020
Actual
Date of last data collection
Anticipated
11/01/2021
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14681 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment postcode(s) [1] 27713 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 303641 0
University
Name [1] 303641 0
University of Sydney
Country [1] 303641 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Brain and Mind Centre
94 Mallett St, Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 304490 0
None
Name [1] 304490 0
Address [1] 304490 0
Country [1] 304490 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304166 0
The University of Sydney Human Research Ethics Committee 2
Ethics committee address [1] 304166 0
Level 3, F23 Administration Building
The University of Sydney
NSW 2006 Australia
Ethics committee country [1] 304166 0
Australia
Date submitted for ethics approval [1] 304166 0
27/05/2019
Approval date [1] 304166 0
26/08/2019
Ethics approval number [1] 304166 0

Summary
Brief summary
Research has shown that exposure-based treatments are the most effective in treating anxiety and fear-based disorders. However, this treatment has been stuck with its improvement in efficacy for years and more than one third of patients do not respond to treatment or experience a relapse of symptoms. Evidence from human and animal studies have shown that acute stress has the potential to add value to these exposure-based treatments by enhancing the learning and memory process. That is, heightened stress
states (induced via pharmacological or behavioural interventions) have been shown to enhance treatment outcomes ( reduce fear symptoms). There is evidence from laboratory studies that stress-related adjuncts to therapy can generalize learning and reduce relapse. However, this has not been investigated in clinical patients and the mechanisms of these effects are unknown. Therefore, this research aims to investigate the use of stress enhancers to optimising exposure therapy for anxiety disorders and it’s potential to reduce
relapse. It will aim to investigate the mechanisms of these effects in order to inform their clinical application. In this study we will determine whether stress may aid psychotherapy of fear and anxiety disorders by modulating attentional processes, stimulating emotional arousal systems (noradrenaline and cortisol) and by acting as an excitatory stimulus to maximise learning (increasing prediction error) . Therefore, this research offers a promising therapeutic tool to improve symptom remission, relapse rates and cost of psychotherapy for anxiety and fear-based disorders.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96022 0
Prof Mark Dadds
Address 96022 0
Brain and Mind centre,
94 Mallett St
Camperdown, NSW, 2050
Country 96022 0
Australia
Phone 96022 0
+61 2 9114 4321
Fax 96022 0
Email 96022 0
[email protected]
Contact person for public queries
Name 96023 0
Ms Elpiniki Andrew
Address 96023 0
Brain and Mind centre,
94 Mallett St
Camperdown, NSW, 2050
Country 96023 0
Australia
Phone 96023 0
+61 430 531 090
Fax 96023 0
Email 96023 0
[email protected]
Contact person for scientific queries
Name 96024 0
Ms Elpiniki Andrew
Address 96024 0
Brain and Mind centre,
94 Mallett St
Camperdown, NSW, 2050
Country 96024 0
Australia
Phone 96024 0
+61 430 531 090
Fax 96024 0
Email 96024 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.