Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001327673
Ethics application status
Approved
Date submitted
21/11/2023
Date registered
19/12/2023
Date last updated
4/04/2024
Date data sharing statement initially provided
19/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The Wellbeing Neuro Course: Comparing clinician-guided versus self-guided online mental health care for adults with epilepsy
Scientific title
A comparative effectiveness trial of digital mental health care models on depression and anxiety symptoms for adults with epilepsy
Secondary ID [1] 309156 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 329273 0
Depression 329274 0
Anxiety 329275 0
Condition category
Condition code
Neurological 326224 326224 0 0
Epilepsy
Mental Health 326225 326225 0 0
Anxiety
Mental Health 326226 326226 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is the Wellbeing Neuro Course, which will be delivered under two models of care:
Arm 1 - Guided Treatment, and
Arm 2 - Unguided Treatment.

The Wellbeing Neuro Course is an internet-delivered psychological intervention developed at the eCentreClinic. Participants will be provided with login details and will access and complete the course online from home. It consists of:
(a) 6 online lessons provided over 10 weeks. The lessons will include information about identifying symptoms of poor wellbeing including mental health and cognitive difficulties, and teach practical skills for their self-management including: managing thoughts, low mood and anxiety, problem solving, memory and attention, and activity and fatigue levels. The intervention includes guidance and examples on how to adopt core psychological skills into one’s day-to-day life, including three comprehensive case stories of adults with neurological disorders.
(b) Optional worksheets for each lesson to aid the practice of core skills. Participants are strongly encouraged but not required to complete these worksheets throughout the course.
(c) Optional additional written resources, which include information about other important skills, such as problem solving common cognitive difficulties, assertiveness and communication skills and techniques for managing sleep difficulties. Participants are encouraged but not required to read through these relevant written resources.

The Wellbeing Neuro Course is based on cognitive behaviour therapy (CBT) principles and teaches evidence-based skills for managing the impacts of neurological disorders on day-to-day activities and overall mental health. Each lesson takes between 10 and 20 minutes to complete and it is suggested that participants read each lesson at least twice and spend approximately 4 hours, across the week, practicing the skills taught.

Participants will be encouraged to complete a lesson every 10 days and complete some basic home based activities in the following 10 days. All lessons can be downloaded and printed. Participants are encouraged to complete the course with a support person if available (e.g., partner, carer).

Adherence (e.g., lesson completion, lesson views) will be monitored via the eCentreClinic software, which is used to provide the Wellbeing Neuro Course.

The efficacy of the Wellbeing Neuro Course will be examined when delivered under two models of care, which comprise the two treatment arms of this study:

Arm 1: Guided Treatment (n=150). In addition to the online Wellbeing Neuro Course detailed above, participants allocated to this group will have access to support from a mental health clinician. All mental health clinicians will be employed by Macquarie University or one of its entities (e.g., MQ Health), and will be provided with training and supervision from a senior psychologist. Participants in the Guided Treatment Group will be informed that their clinician will be available for around 15 minutes each week and will contact them throughout the course via telephone or secure messaging systems, with more clinician time available when clinically indicated. Clinicians will be available to: (1) answer questions; (2) summarise content; (3) encourage skills practice and reinforce progress; (4) enquire about participants’ use of the skills; and (5) normalise challenges. In addition, clinicians will send detailed assessments and treatment progress reports to participants' primary epilepsy health professional.

Arm 2: Unguided Treatment (n=150). Participants allocated to this group will receive the Wellbeing Neuro Course detailed above, but will be informed that they will not receive contact during the course unless they experience technical difficulties or a mental health emergency.
Intervention code [1] 325605 0
Treatment: Other
Comparator / control treatment
There will be a Treatment-as-usual Waitlist Control (TAU-WLC) group (n=75) which will receive full access to the treatment three months after the two Treatment Groups finish the Wellbeing Neuro Course (i.e. at the three month follow-up for the Treatment Groups). Participants in the TAU-WLC group will continue to receive their normal treatment and care from their regular health practitioners and general use of the health-care system prior to partaking in the Wellbeing Neuro Course. After the Treatment Group has finished the three month follow-up questionnaires, participants in the TAU-WLC group will be able to start receiving the intervention. The TAU-WLC will be able to choose whether to receive the course under a Guided or Unguided model of care.
Control group
Active

Outcomes
Primary outcome [1] 334113 0
Patient Health Questionnaire 9-Item (PHQ-9), a measure of depressive symptoms.
Timepoint [1] 334113 0
Assessment
Baseline (pre-intervention)
The PHQ-2 will be administered weekly for 9 weeks throughout the intervention period
11 weeks (post-intervention/ primary endpoint)
3-months post-intervention completion
12-months post-intervention completion
Primary outcome [2] 334114 0
Generalized Anxiety Disorder 7-Item (GAD-7), a measure of anxiety symptoms.
Timepoint [2] 334114 0
Assessment
Baseline (pre-intervention)
The GAD 2-Item will be administered weekly for 9 weeks throughout the intervention period
11 weeks (post-intervention/primary endpoint)
3-months post-intervention completion
12-months post-intervention completion
Secondary outcome [1] 419401 0
Neuro-QoL (Quality of Life in Neurological Disorders), a measure of the physical, mental, and social effects experienced by people with neurological conditions. We will administer the following subscale:
(1) Cognitive Function: 8 items measuring perceived cognitive difficulties.
Timepoint [1] 419401 0
Baseline (pre-intervention)
11 weeks (post-intervention)
3-months post-intervention completion
12-months post-intervention completion
Secondary outcome [2] 419404 0
Neurological Depressive Disorders Inventory-Epilepsy (NDDI-E), an epilepsy specific depression screener, which does not include any items that may be confounded by seizure phenomena and common side effects of medications.
Timepoint [2] 419404 0
Assessment
Baseline (pre-intervention)
The NDDI-E suicide item will be administered weekly for 9 weeks throughout the intervention period.
11 weeks (post-intervention)
3-months post-intervention completion
12-months post-intervention completion
Secondary outcome [3] 419405 0
Brief Epilepsy Anxiety Survey Instrument (BrEASI), an epilepsy specific anxiety screener which does not include any items that may be confounded by seizure phenomena and common side effects of medications.
Timepoint [3] 419405 0
Assessment
Baseline (pre-intervention)
11 weeks (post-intervention)
3-months post-intervention completion
12-months post-intervention completion
Secondary outcome [4] 419411 0
Compensatory Cognitive Strategies Questionnaire (CCSQ), a purpose-built measure to assess the use of compensatory cognitive strategies before and after the intervention.
Timepoint [4] 419411 0
Baseline (pre-intervention)
11 weeks (post-intervention)
3-months post-intervention completion
12-months post-intervention completion
Secondary outcome [5] 419412 0
Treatment Satisfaction Questionnaire (TSQ), a purpose-built measure to assess the acceptability of online treatment Courses and to measure participants’ satisfaction with treatment.
Timepoint [5] 419412 0
11 weeks (post-intervention)
Secondary outcome [6] 419608 0
Recovering Quality of Life 10-item (ReQoL-10) will be used to measure health-related quality of life for the cost-utility analyses.
Timepoint [6] 419608 0
Baseline (pre-intervention)
11 weeks (post-intervention)
3-months post-intervention completion
Secondary outcome [7] 423474 0
EQ-5D-5L, a brief measure of quality of life that can be converted into utility values for cost-effectiveness analyses.
Timepoint [7] 423474 0
Baseline (pre-intervention)
11 weeks (post-intervention)
3-months post-intervention completion
Secondary outcome [8] 423478 0
Use of Services Questionnaire, a purpose-built measure based on the Treatment Inventory of Costs in Psychiatric Patients (TIC-P) will be used to capture health service and medication use.
Timepoint [8] 423478 0
Baseline (pre-intervention)
11 weeks (post-intervention)
3-months post-intervention completion
Secondary outcome [9] 427927 0
A purpose-built measure for participants' healthcare professionals regarding perceived usefulness and acceptability of the intervention.
Timepoint [9] 427927 0
11 weeks (post-intervention)
Secondary outcome [10] 429118 0
World Health Organisation Disability Assessment Schedule 2.0 (WHODAS-2), a measure of disability associated with living with a chronic health condition.
Timepoint [10] 429118 0
Assessment
Baseline (pre-intervention)
11 weeks (post-intervention)
3-months post-intervention completion
12-months post-intervention completion
Secondary outcome [11] 429119 0
Seizure Frequency Questionnaire (SFQ).This is a brief 4-item purpose-built measure to assess participant’s perception of seizure control and average frequency of seizures
Timepoint [11] 429119 0
Assessment
Baseline (pre-intervention)
Seizure Frequency- 1 item will be administered weekly for 9 weeks throughout the intervention period
11 weeks (post-intervention)
3-months post-intervention completion
12-months post-intervention completion

Eligibility
Key inclusion criteria
(1) Confirmed diagnosis of epilepsy.
(2) Experiencing difficulties with their emotional health.
(3) 18+ years of age.
(4) Living in Australia.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Imminently suicidal or unable to keep themselves safe.
(2) Are experiencing severe cognitive difficulties with day-to-day memory, attention and ability to learn basic information.
(3) Are unable to read and understand English.
(4) Do not have access to the internet.

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 who wish to apply for the treatment will do so via the clinic's website (www.ecentreclinic.org.au) and will be followed-up with a telephone interview to confirm their suitability for the trial and to conduct a structured clinical interview for DSM-5 Mood and Anxiety Disorders (QuickSCID-5) . Importantly, the allocation sequence will be concealed from study personnel who determine participant eligibility and enrollment. These personnel will only have access to the allocation sequence after participants are successfully enrolled into the trial. Concealment will occur through visibly 'blacking-out' columns in Excel which will hide the group allocation of the participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised in a ratio of 2:2:1 to immediate guided treatment, immediate unguided treatment, and treatment-as-usual-wait-list control. The 2:2:1 randomisation sequence with smaller weighting for control participants, is related to saving recruitment resources given that previous Phase II findings demonstrate that the control group does not improve. Randomisation will be performed by an independent researcher using online computer software (www.random.org) using permuted blocks of 6 with 2:2:1 allocation. Participants will be stratified based on referral source..
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size was determined in line with expert guidelines and calculations included data from a previous RCT, which observed a standard rate of symptom change on our primary outcomes of depression and anxiety of 24% each. We utilised specialised longitudinal software to account for our proposed generalised estimation equations models (GEE). Power analyses were conducted with Type I error was set at a=0.05 and Type II error at ß=80% and utilized a DELTA2 methodology.

Our superiority analyses will compare the two active treatment groups with the TAU-WLC. We calculated this requires a sample size of 125:80 (e.g., Unguided: Control) to detect a difference in the rate of symptom change as small as 11% on the mental health primary outcomes from baseline to post-treatment . Our non-inferiority analyses will compare the Unguided and Guided treatment groups. In line with power estimation for non-inferiority thresholds in mental health trials we considered a difference of 50% of the standard rate of symptom reduction in depression and anxiety symptoms (i.e., 12% reduction in symptoms at post-treatment) as the prespecified margin of non-inferiority. Based on these margins we require a sample size of 125:125 (Unguided: Guided).

Utilising a conservative attrition estimate of 20%, a final larger sample of 150:150:75 (Guided: Unguided” Control) was decided.

We will report clinical efficacy findings with and without data imputations under the intention-to-treat analysis and missing data assumptions. The intention-to-treat approach will involve all outcomes being evaluated and imputed for all participants who were randomized and provided baseline data, consistent with previous research. Clinical efficacy will be assessed utilising longitudinal GEE models to assess changes in the primary and secondary clinical outcomes over time and between the three groups.

To determine whether post-treatment improvements are maintained over time within-group time effects will be examined at 3 and 12-month follow-up. For all analyses, the level of statistical significance will be set at alpha 0.05. All GEE models will include log link function and gamma scale parameters to account for the positive skew in the clinical outcome data.

Clinical significance will be reported in several ways. Consistent with previous research we will calculate the average percentage improvement (e.g. pre-treatment mean score – post-treatment mean score/pre- treatment mean score) for each group from pre-treatment to post-treatment and 3-month and 12-month follow-up, for the clinical outcomes, using the estimated marginal means from the GEE models. Second, the proportion of participants achieving a clinical improvement (defined as greater than or equal to 25%) and large clinical improvement (defined as greater than or equal to 50%) on the primary outcomes will be calculated and compared between groups using Generalized Linear Models using appropriate statistical models (e.g., GEE). In addition, deterioration (i.e., symptom increase at post-treatment of greater than or equal to 30% and within the clinical range) will be compared between groups. Based on these outcomes, the number needed to treat (NNT) will be calculated. Finally, Hedges g effect sizes will be calculated for the between-group and within-groups effects.

Sensitivity analyses will be conducted for primary outcomes based on DSM-5 diagnostic status and baseline symptom severity. Additionally, we may examine clinically important subgroups based on treatment adherence and any unbalanced or clinically important baseline characteristics.

Healthcare resource use data for participants in each trial arm will be obtained from the Australian Institute of Health and Welfare (AIHW). Differences in healthcare costs will be compared to differences in health-related quality of life . Cost effectiveness will be reported as an incremental cost effectiveness ratio (ICER), which will be compared to an implicit threshold derived from recommendations made by the Australian Government’s Pharmaceutical Benefits Advisory Committee, Uncertainty around the ICER will be explored using deterministic and probabilistic sensitivity analyses, which will be reported on a cost effectiveness acceptability curve.

We will assess the potential impact on government budgets from scaling up the most cost-effective intervention within Australia. This will include estimating how many patients could benefit from the intervention and potential changes to the use of other services. We will develop a Health Economics Analysis Plan to guide the economic evaluation and align our modelling approach with the ISPOR Good Research Practices for cost effectiveness analysis. Reporting would adhere to the Consolidated Health Economic Evaluation Reporting Standards 2022 and evaluation reporting methods.




Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/02/2024
Actual
16/02/2024
Date of last participant enrolment
Anticipated
1/12/2029
Actual
Date of last data collection
Anticipated
1/12/2030
Actual
Sample size
Target
375
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 313356 0
Government body
Name [1] 313356 0
National Health and Medical Research Council
Country [1] 313356 0
Australia
Funding source category [2] 313370 0
University
Name [2] 313370 0
Macquarie University
Country [2] 313370 0
Australia
Primary sponsor type
Individual
Name
Dr. Milena Gandy
Address
School of Psychological Sciences,Macquarie University Wallumattagal Campus Balaclava RoadMacquarie ParkNSW, 2109
Country
Australia
Secondary sponsor category [1] 315105 0
University
Name [1] 315105 0
Macquarie University
Address [1] 315105 0
Macquarie University Wallumattagal Campus Balaclava RoadMacquarie ParkNSW, 2109
Country [1] 315105 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312578 0
Macquarie University Medical Sciences Human Research Ethics Committee (MQ HREC)
Ethics committee address [1] 312578 0
Ethics committee country [1] 312578 0
Australia
Date submitted for ethics approval [1] 312578 0
31/05/2023
Approval date [1] 312578 0
16/06/2023
Ethics approval number [1] 312578 0

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

Contacts
Principal investigator
Name 125158 0
Dr Milena Gandy
Address 125158 0
School of Psychological Sciences,Balaclava Road, North RydeMacquarie University.NSW, 2109
Country 125158 0
Australia
Phone 125158 0
+61298504152
Fax 125158 0
Email 125158 0
[email protected]
Contact person for public queries
Name 125159 0
Milena Gandy
Address 125159 0
School of Psychological Sciences,Balaclava Road, North RydeMacquarie University.NSW, 2109
Country 125159 0
Australia
Phone 125159 0
+61298504152
Fax 125159 0
Email 125159 0
[email protected]
Contact person for scientific queries
Name 125160 0
Milena Gandy
Address 125160 0
School of Psychological Sciences,Balaclava Road, North RydeMacquarie University.NSW, 2109
Country 125160 0
Australia
Phone 125160 0
+61298504152
Fax 125160 0
Email 125160 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Any non-identifiable data necessary to verify the outcomes reported in any published reports by the research team.
When will data be available (start and end dates)?
Data will be made available after any original reports have been published. There will be no end date to the availability.
Available to whom?
Researchers working with the approval and under the governance of a Human Research Ethics Committee or Standards Committee.
Available for what types of analyses?
Any analyses required to verify the outcomes reported in published reports.
How or where can data be obtained?
Data will be made available following formal request to the chief investigator using a mechanism that is satisfactory for the Macquarie University Human Research Ethics Committee (providing governance for the current research) and any other Research Standards or Human Research Ethics Committee's involved. Data can be obtained by e-mailing the chief investigator ([email protected])


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.