Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000421437
Ethics application status
Approved
Date submitted
10/04/2025
Date registered
8/05/2025
Date last updated
8/05/2025
Date data sharing statement initially provided
8/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating Biological and Psychological Factors to Guide Treatment Selection for PTSD: A Randomised Control Trial ('Decode')
Scientific title
Investigating Biopsychosocial Markers to Guide Treatment Selection for PTSD: A Randomised Control Trial ('Decode')
Secondary ID [1] 313532 0
Nil known
Universal Trial Number (UTN)
Trial acronym
DECODE
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Posttraumatic stress disorder (PTSD) 335998 0
Condition category
Condition code
Mental Health 332578 332578 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study aims to understand biopsychosocial markers of treatment response to better match patients to evidence-based psychological interventions which address the presence and severity of PTSD.
It investigates massed Unified Protocol (UP), a transdiagnostic non-trauma focused cognitive behavioural therapy. UP is a manualised psychological treatment consisting of ten, 80-minute individual sessions delivered by a trained clinician. The UP has eight modules which cover: (1) goal setting/maintaining motivation, (2) psychoeducation about emotions, (3) mindful emotional awareness, (4) cognitive flexibility, (5) emotion driven behaviours, (6) interoceptive exposures, (7) emotion exposures, and (8) relapse prevention. Consistent with the delivery of massed UP as in other trials (e.g., Sherrill et al., 2024), instead of having weekly sessions, the sessions will be condensed into a more limited time-frame (i.e., daily for two weeks). The UP treatment will be delivered face-to-face at the Phoenix Traumatic Stress Research Clinic at the Royal Melbourne Hospital (Royal Park) or via telehealth using videoconferencing.
To maintain fidelity to the UP treatment protocol, we hold monthly dedicated UP supervision with an expert UP supervisor. We also audio record 10% of our treatment sessions (allocated randomly), which are evaluated for fidelity.
Intervention code [1] 330119 0
Treatment: Other
Comparator / control treatment
The active comparison condition is massed Prolonged Exposure (PE) (Foa et al., 2007). PE is a cognitive behavioural intervention that involves helping the person gradually confront traumatic memories and avoided situations in a supportive, controlled and safe environment, to reduce associated fear and modify interpretations of the traumatic event that are impeding recovery. The manualised massed PE treatment involves 10x80-minute sessions delivered to the individual by a trained clinician. The PE treatment will be delivered face-to-face at the Phoenix Traumatic Stress Research Clinic at the Royal Melbourne Hospital (Royal Park) or via telehealth using videoconferencing.
To maintain fidelity to the PE treatment protocol, we hold monthly dedicated PE supervision with an expert PE supervisor. We also audio record 10% of our treatment sessions (allocated randomly), which are evaluated for fidelity.
Control group
Active

Outcomes
Primary outcome [1] 340112 0
Severity of PTSD symptoms
Timepoint [1] 340112 0
2 weeks post-treatment
Primary outcome [2] 340113 0
Severity of PTSD symptoms
Timepoint [2] 340113 0
3 months post-treatment
Secondary outcome [1] 442781 0
Severity of Depression
Timepoint [1] 442781 0
3 months post-treatment
Secondary outcome [2] 442779 0
Severity of depression
Timepoint [2] 442779 0
2 weeks post-treatment
Secondary outcome [3] 442776 0
Severity of anxiety
Timepoint [3] 442776 0
3 months post-treatment
Secondary outcome [4] 442778 0
Severity of anxiety
Timepoint [4] 442778 0
2 weeks post-treatment

Eligibility
Key inclusion criteria
1. Aged 18+
2. English comprehension at a level to make informed consent
3. Meeting diagnostic threshold for PTSD after a traumatic experience (experienced at any time point in their life)
4. Able to commit the time to the intensive nature of treatment delivery
5. If on psychotropic medication, on a stable dose for the last 4 weeks and not intending to change for the duration of the treatment phase
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cognitive impairment, including from serious traumatic brain injury
2. Current psychosis, mania or active suicidality and/or other serious risk issue
3. Severe alcohol or substance use disorders
4. Currently undergoing active psychological treatment for a mental health condition

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)
Participants will self-refer and undergo an eligibility assessment with a trained intake officer. Once they are deemed eligible, participants will be randomised into a treatment condition using a coded number system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation where the groups vary between of 6 and 12. This was created and uploaded onto RedCap by independent statisticians.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculations were based on the primary aim of testing non-inferiority of massed Unified Protocol vs massed Prolonged Exposure on the primary outcome of changes in CAPS-5 total scores. Consistent with other trials in the area (Green et al., 2008; Litz et al., 2021; Morland et al., 2015; Nidich et al., 2018; Sloan et al., 2021; Sloan, et al., 2016), we will use 10 points as the non-inferiority margin – or the maximum amount by which UP can be worse than PE without having a clinical meaningful difference. Our assumptions include standard values of P = .05, power = 0.80, and an SD of 20 for the CAPS-5, consistent with past non-inferiority trials. Power calculations indicate that a sample size of 116 provides power greater than 0.80 to detect non-inferiority. This sample size has been increased by 20% to account for loss to follow up across time, resulting in the target sample size of 140 clients.
The non-inferiority hypothesis will be evaluated by examining whether the entire 95% confidence interval for the difference in mean change scores from baseline to post-treatment between massed Unified Protocol and Prolonged Exposure is less than a margin of 10 points. Between-condition (Cohen d and odds ratio), and within-condition (standardized mean gain scores) effect sizes will also be calculated to characterize treatment effects on PTSD symptoms and diagnostic rates at 2 weeks posttreatment and the 3 month follow-up. Growth curve models will be specified to characterize within-condition effects of treatment on PTSD. Additionally, linear mixed effects models will be used to investigate the impact of time and group allocation on secondary outcome measures including symptoms of anxiety (GAD-7) and depression (PHQ-9). In all linear mixed effects models, baseline scores will be included as a covariate. All analyses will be conducted in accordance with intention-to-treat principles. Missing data in all analyses will be handled using multiple imputation procedures. The estimates from the analyses of the imputed data sets will be combined to obtain pooled common estimates and corresponding confidence intervals using Rubin's rules.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/05/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
140
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 317988 0
Government body
Name [1] 317988 0
National Health and Medical Research Council
Country [1] 317988 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 320748 0
None
Name [1] 320748 0
Address [1] 320748 0
Country [1] 320748 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316657 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 316657 0
Ethics committee country [1] 316657 0
Australia
Date submitted for ethics approval [1] 316657 0
27/06/2024
Approval date [1] 316657 0
26/08/2024
Ethics approval number [1] 316657 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 138558 0
Prof Meaghan O'Donnell
Address 138558 0
Phoenix Australia, Level 3, Alan Gilbert Building, 161 Barry Street, Carlton VIC 3053
Country 138558 0
Australia
Phone 138558 0
+61 3 834 40193
Fax 138558 0
Email 138558 0
[email protected]
Contact person for public queries
Name 138559 0
Dr Hope O'Brien
Address 138559 0
Phoenix Australia, Level 3, Alan Gilbert Building, 161 Barry Street, Carlton VIC 3053
Country 138559 0
Australia
Phone 138559 0
+61 3 9035 5599
Fax 138559 0
Email 138559 0
[email protected]
Contact person for scientific queries
Name 138560 0
Prof Meaghan O'Donnell
Address 138560 0
Phoenix Australia, Level 3, Alan Gilbert Building, 161 Barry Street, Carlton VIC 3053
Country 138560 0
Australia
Phone 138560 0
+61 3 9035 5599
Fax 138560 0
Email 138560 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: Email Meaghan O'Donnell at [email protected]

Are there extra considerations when requesting access to individual participant data?
No


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.