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Trial registered on ANZCTR


Registration number
ACTRN12625000271404
Ethics application status
Approved
Date submitted
19/02/2025
Date registered
10/04/2025
Date last updated
10/04/2025
Date data sharing statement initially provided
10/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Cognitive Bias Modification for Interpretation (CBM-I) in People with Painful Endometriosis
Scientific title
Randomised Controlled Trial of Cognitive Bias Modification for Interpretation (CBM-I) on Pain Impact and Severity in Individuals with Painful Endometriosis
Secondary ID [1] 313905 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 336597 0
Condition category
Condition code
Reproductive Health and Childbirth 333101 333101 0 0
Other reproductive health and childbirth disorders
Inflammatory and Immune System 333102 333102 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For this study, we will adopt a double-blind randomized controlled trial methodology, whereby the individuals with endometriosis will be randomly allocated to one of three groups:
(1) Cognitive Bias Modification for interpretation (CBM-I) intervention
(2) Imagery enhanced CBM-I intervention
(3) Placebo control.

The intervention for the treatment groups is Cognitive Bias Modification for Interpretation (CBM-I), which aims to train individuals to make benign rather than health-threat related interpretations of ambiguous information. In this intervention, participants will be presented with 27 ambiguous scenarios. These scenarios have been validated in prior research with individuals with a range of pelvic pain related conditions.

Each of the scenarios could be resolved with a pelvic pain related or benign solution. Each scenario will be followed by a word fragment that the participant needs to complete. To train participants to make benign interpretations, all word fragments will represent benign, rather than pelvic pain related outcomes. After each scenario, participants will be asked a comprehension question and to indicate whether the question was related to the previous scenario (‘Yes’ or ‘No’). Participants will be given ‘correct’ feedback when they endorse a benign (not pelvic pain-related) response. If participants endorse a pelvic pain-related resolution, they will be given ‘incorrect’ feedback.

The CBM-I training itself in terms of the task, training sessions and time and reinforcement of solutions is the same for the two CBM-I conditions. The two CBM-I conditions differ with respect to the pre training practice exercise, the task instructions, and the post scenario fidelity question. These differences are explained below.

CBM-I group (CBM-I)

Prior to the training, participants in the CBM-I group will receive an introduction to verbal processing and undergo a brief verbal processing training exercise to practice verbal processing (e.g., Holmes et al., 2006; Blackwell et al., 2015). Participants will be presented with sentences about a lemon and asked to focus on the words and meanings of sentences (Holmes et al., 2006). During the CBM-I intervention, these participants will be instructed to pay attention to the words and meanings of the scenarios (Holmes et al., 2006).
To assess the degree to which participants focus on words and their meanings throughout the training, after each scenario, participants will also be asked “How difficult was it to understand the meaning of the description?” and will respond on a scale from 1 (not at all difficult) to 5 (extremely difficult) in line with Blackwell et al., (2015) and Holmes et al. (2006).

Imagery enhanced CBM-I group (IE_CBM-I)

Prior to the training, participants in the IE_CBM-I group will receive an introduction to mental imagery and undergo a brief imagery training exercise to practice generating mental imagery (e.g., Holmes et al., 2006; Blackwell et al., 2015). As per Holmes et al. (2008), participants will be asked to imagine they are cutting a lemon. Details of the mental imagery training are included in the study materials. During the CBM-I trial, these participants will also be instructed to imagine themselves in each scenario, as if actively involved, seeing things through their own eyes (Holmes et al., 2006).

To assess the degree to which participants are using imagery throughout the training, after each scenario, participants will also be asked “How vividly could you imagine the scenario described?” and will respond on a scale from 1 (not at all vivid) to 5 (extremely vivid), in line with Blackwell et al., (2015) and Holmes et al. (2006).

The intervention will be delivered entirely online by an institutional software program (Qualtrics) that will randomly allocate participants to one of the three groups. There is no direct researcher input.. Participants complete the intervention individually via smartphone or computer.

CBM-I will be delivered four times to each participant during the entire study.

Time frame:
Introduction (5 minutes) + CBM-I training session 1 (10-15 minutes): day 1 of the study
Introduction reminder (2 minutes) + CBM-I training session 2 (10-15 minutes): day 8 of the study
Introduction reminder (2 minutes) + CBM-I training session 3 (10-15 minutes): day 15 of the study
Introduction reminder (2 minutes) + CBM-I training session 4 (10-15 minutes): day 22 of the study

The first introduction will take about 5 minutes to complete, the introduction reminders before sessions 2-4 will take 2 minutes, and each of the 4 training sessions will take approximately 10-15 minutes to complete.

The number of training sessions completed is recorded for each participant to monitor adherence to the intervention.
Intervention code [1] 330497 0
Behaviour
Comparator / control treatment
Placebo group

In the placebo group, participants will be presented with the same scenarios as the CBM-I groups, but 50% of trials will reinforce a benign association, and 50% of trials will reinforce a pelvic pain related interpretation. The benign versus endometriosis resolutions will be randomised across the task. The placebo condition helps to account for the potential impact of mere exposure to the stimuli and is well matched in terms of number of trials, sessions, and other major characteristics.

As in the CBM-I group, prior to the CBM-I training, participants in the placebo group will receive an introduction to verbal processing and undergo a brief verbal processing training exercise to practice verbal processing (e.g., Holmes et al., 2006; Blackwell et al., 2015).

To assess the degree to which participants focus on words and their meanings throughout the training, after each scenario, participants will also be asked “How difficult was it to understand the meaning of the description?” and will respond on a scale from 1 (not at all difficult) to 5 (extremely difficult) in line with Blackwell et al., (2015) and Holmes et al. (2006).

The placebo intervention will be delivered four times to each participant during the entire study. There is no direct researcher input.. Participants complete the intervention individually via smartphone or computer.

Time frame
The training schedule for the placebo sessions follows that of the CBM-I sessions, as below:
Introduction (5 minutes) + placebo training session 1 (10-15 minutes): day 1 of the study
Introduction reminder (2 minutes) + placebo training session 2 (10-15 minutes): day 8 of the study
Introduction reminder (2 minutes) + placebo training session 3 (10-15 minutes): day 15 of the study
Introduction reminder (2 minutes) + placebo training session 4 (10-15 minutes): day 22 of the study

The first introduction will take about 5 minutes to complete, the introduction reminders before sessions 2-4 will take 2 minutes, and each of the 4 training sessions will take approximately 10-15 minutes to complete.

The number of training sessions completed is recorded for each participant to monitor adherence to the intervention.
Control group
Placebo

Outcomes
Primary outcome [1] 340637 0
Pain Severity
Timepoint [1] 340637 0
Primary outcome of pain severity will be assessed at the following timepoints: 1) day 1 (pre training/baseline), day 8, day 15, day 22 (end of training), day 36 (follow-up 1: 2 week follow up), day 112 (follow-up 2: 3 month follow up). The primary timepoint is day 36 (follow-up 1: 2 week follow up).
Primary outcome [2] 340638 0
Pelvic Pain Impact
Timepoint [2] 340638 0
Primary outcome of pain impact will be assessed at the following timepoints: 1) day 1 (pre training/baseline), day 8, day 15, day 22 (end of training), day 36 (follow-up 1: 2 week follow up), day 112 (follow-up 2: 3 month follow up). The primary timepoint is day 36 (follow-up 1/2 week follow up)
Secondary outcome [1] 444679 0
Heath-related quality of life (HRQoL)
Timepoint [1] 444679 0
Secondary outcome of HRQoL will be assessed at the following timepoints: 1) baseline (day 1), day 22 (end of training), day 36 (follow-up 1: 2 week follow up), day 112 (follow-up 2: 3 month follow up)
Secondary outcome [2] 444680 0
The depression, anxiety and stress subscales from the Depression Anxiety and Stress Scale 21 (DASS-21) will be used to measure the emotional states of depression, anxiety, and stress, respectively.
Timepoint [2] 444680 0
Secondary outcome of DASS-21 will be assessed at the following timepoints: 1) baseline (day 1), day 22 (end of training), day 36 (follow-up 1: 2 week follow up), day 112 (follow-up 2: 3 month follow up)
Secondary outcome [3] 444681 0
Fear of Progression
Timepoint [3] 444681 0
Secondary outcome of fear of progression will be assessed at the following timepoints: 1) baseline (day 1), day 22 (end of training), day 36 (follow-up 1: 2 week follow up), day 112 (follow-up 2: 3 month follow up)

Eligibility
Key inclusion criteria
Eligibility will be determined via pre-screening questionnaire on Qualtrics.
To be included, participants must meet the following:
1. Age 18 or older
2. Have a confirmed endometriosis diagnosis, or a provisional endometriosis diagnosis (i.e. participants must have had consultation/s with medical professionals who have suggested they may have endometriosis based on their symptoms and experience)
3. Experience pain associated with endometriosis
4. Access to internet and a computer or smartphone over a 3-month study period
5. Fluent in English
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
None

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 software program ‘Qualtrics’ will be used as a platform to deliver the training, as well as the questionnaires, information statement, consent and debrief. Qualtrics has an inbuilt randomisation function, which will electronically allocate each participant to one of 2 groups.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation. In this case Qualtrics, a web based software will be used.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Using the effect size of two-week post-treatment outcomes for pain intensity found by Sharpe et al. (2023) d=0.39, it was calculated that 292 participants (98 per group) would be needed to have sufficient power (0.8) with alpha of 0.05. This sample size calculation accounted for 50% drop out. The appropriate sample size was calculated using G*Power3 software (Faul et al., 2007).

We will conduct statistical analyses to investigate between group differences in pre-post training reductions in pain severity and pain interference, and secondary outcomes. We will compare the treatment groups (CBM-I and IE_CBM-I) to placebo, and the two treatment groups (CBM-I vs IE_CBM-I).
As such, our primary analyses will be a series of linear mixed model regressions (LMMR) to examine the effect of intervention group, time, and group x time on the dependent variables. The co-primary outcomes are pain severity and pain interference and the primary timepoints are post-treatment and two-week follow-up. Our primary analysis will be intention to treat, and we will impute missing values. As this is a remotely delivered intervention and we anticipate dropouts of 50% based on our previous studies, we will also conduct a per protocol analysis, including only those participants who completed at least half of the treatment (2 out of 4 training sessions).

Using SPSS, and the PROCESS macro developed by Hayes (2013), we will conduct mediation analyses to determine 1) whether the differences between treatment groups and placebo over time can be accounted for by the induced interpretation bias, and 2) whether the differences between CBM-I and imagery enhanced CBM-I can be accounted for by imagery vividness. These would confirm the proposed mechanisms of treatment. As such, we would determine whether 1) induced bias and 2) induced imagery vividness mediated the relationships between group assignment and pain outcomes, when controlling for baseline levels of pain outcomes.

Our previous research suggests that people are not able to determine whether or not they received the intervention or placebo, which ensures that blinding can be maintained throughout the trial (Sharpe et al., 2023). We will ask participants at the end of the trial what group they believe they were assigned to.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/04/2025
Actual
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
31/10/2025
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 26867 0
United Kingdom
State/province [1] 26867 0

Funding & Sponsors
Funding source category [1] 318377 0
University
Name [1] 318377 0
Funded through University of Sydney School of Psychology HDR support funds
Country [1] 318377 0
Australia
Funding source category [2] 318626 0
Other
Name [2] 318626 0
Australian Research Council Grants (DP210101827 & DE230100206)
Country [2] 318626 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 320776 0
None
Name [1] 320776 0
Address [1] 320776 0
Country [1] 320776 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317009 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 317009 0
Ethics committee country [1] 317009 0
Australia
Date submitted for ethics approval [1] 317009 0
07/11/2024
Approval date [1] 317009 0
17/01/2025
Ethics approval number [1] 317009 0
2024/HE001666

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

Contacts
Principal investigator
Name 139722 0
Dr Jemma Todd
Address 139722 0
Room 318 Brain and Mind Centre Mallett St building F M02F, The University of Sydney, NSW, 2006
Country 139722 0
Australia
Phone 139722 0
+610291144359
Fax 139722 0
Email 139722 0
[email protected]
Contact person for public queries
Name 139723 0
Brydee Pickup
Address 139723 0
Level 3 Brain and Mind Centre Mallett St building F M02F, The University of Sydney, NSW, 2006
Country 139723 0
Australia
Phone 139723 0
+447810786143
Fax 139723 0
Email 139723 0
[email protected]
Contact person for scientific queries
Name 139724 0
Dr Jemma Todd
Address 139724 0
Room 318 Brain and Mind Centre Mallett St building F M02F, The University of Sydney, NSW, 2006
Country 139724 0
Australia
Phone 139724 0
+610291144359
Fax 139724 0
Email 139724 0
[email protected]

Data sharing statement
Will the study consider sharing 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.