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Trial registered on ANZCTR


Registration number
ACTRN12613001334796
Ethics application status
Approved
Date submitted
2/12/2013
Date registered
5/12/2013
Date last updated
27/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
COgnitive bias modification to Prevent dEpression (COPE trial)
Scientific title
Cognitive Bias Modification (CBM) for the Prevention of Depression Among People with Subsyndromal Depressive Symptoms.
Secondary ID [1] 283669 0
Nil
Universal Trial Number (UTN)
Trial acronym
COPE trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depressive disorder 290622 0
Subsyndromal depression 290636 0
Condition category
Condition code
Mental Health 291014 291014 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cognitive bias modification (CBM) delivered via the internet over 12 months: 3 sessions/week during first 4 weeks, 2/week up for an additional 4 weeks, then 1/week up to week 26, once per fortnight up to week 38, and once per month up to week 52.

Eligible participants will be randomly allocated to one of 2 treatment arms: sham or active CBM. CBM sessions will be delivered over a period of 52 weeks (1 year): three times per week for the first 4 weeks, twice weekly for the next 4 weeks (up to week 8), once weekly for the next 18 weeks (up to week 26), once per fortnight for the next 12 weeks, and once per month for the remainder of the follow up period (up to week 52). This delivery schedule is designed to achieve rapid bias modification though initially intensive training, while also encouraging maintenance of the resulting cognitive change through sustained exposure to CBM across an extended period, and by phasing out rather than abruptly terminating the intervention. Each CBM session will be of 40-minute duration, and will be accessed through a password-protected internet site. They will deliver CBM designed to reduce attention to negative information (CBM-A, 20 minutes) and to reduce the negative interpretation of ambiguous stimuli (CBM-I, 20 minutes). On each session, participants will be presented with a pair of emotionally-toned facial images (sad vs neutral or happy) for 500 ms, which will then be replaced by a small white probe (vertical or horizontal line), appearing in the screen position previously occupied by one of these stimuli. Participants will be instructed to use their keyboards to indicate the orientation of this probe as quickly as possible ('V' for vertical, 'H' for horizontal). The probe will then disappear and will be replaced, after 1 second, by another stimulus pair that will commence the next trial. The time to discriminate probe identity will be recorded automatically. In the active CBM-A condition all probes will appear in the opposite screen area from that of the negative stimulus (avoid negativity), while in the control condition probes will appear equally often in the area of the negative and non-negative stimuli. The second half of each 40-minute session will deliver CBM-I using single words and short textual scenarios as ambiguous stimuli. On each trial this ambiguous stimulus will first be presented (e.g. word ‘growth’), followed, 500 ms later, by a fragment of a word that is semantically consistent with one or other meaning of the preceding ambiguity (e.g., ‘t_mour’ or ‘gr_ater’). Participants will be instructed to complete this fragment to yield a word consistent with the meaning of the initial word or sentence, using their keyboard to enter the letter missing from the fragment. The time to solve the word fragments will be recorded automatically. In the active CBM-I condition all fragments will yield only words consistent with non-negative interpretations of the preceding ambiguity, while in the control CBM-I condition fragments will equally often yield words consistent with the negative and non-negative interpretation of this ambiguity. A large bank with thousands of faces, words and textual scenarios that have already been used in other studies is available, and the computer programs are ready for use.

Adherence will be monitored via CBM login log records and the number of completed sessions.
Intervention code [1] 288367 0
Prevention
Comparator / control treatment
Each CBM session will last approximately 40 minutes (20 minutes CBM-A and 20 minutes CBM-I). They will be delivered via the internet over a period of 12 months: 3 sessions/week during first 4 weeks, 2 sessions/week up for an additional 4 weeks (up to week 8), then 1 session/week up to week 26, then 1 session per fortnight up to week 38, and finally 1 session/month up to week 52.

Control sessions will have exactly the same format, duration and sets of stimuli, but the activity will not be systematically avoid negative stimulus or interpretation.
Control group
Active

Outcomes
Primary outcome [1] 290998 0
Clinically significant symptoms of depression, established by a score of 15 or greater on the Patient Health Questionnaire (PHQ-9).
Timepoint [1] 290998 0
Weeks 6, 11, 15, 19, 23, 27, 36, 44, 52.
Primary outcome [2] 290999 0
Major depressive episode according to DSM-V criteria.
Timepoint [2] 290999 0
Weeks 11, 27 and 52.
Secondary outcome [1] 305788 0
Change in the use of antidepressants (either introduction, discontinuation or change in dosage). We will ask participants to list all medications they have used during the preceding 4 weeks, as well as their dosages. We will compare the proportion of people in the active and control CBM groups who have started using antidepressants since the baseline assessment, as well as those who discontinue the use of antidepressants or change the dosage of the medication (increased and decreased dosages).

These data will be collected as part of a self-report questionnaire over the internet before the first CBM session of the relevant week (8, 26 and 52).
Timepoint [1] 305788 0
Weeks 8, 26 and 52
Secondary outcome [2] 305789 0
Change in psychotherapy status (start, cessation, change in frequency). Participants will be asked to complete a questionnaire that includes the following question: 'During the past 4 weeks, have you received professional counselling or psychotherapy?' We will compare the proportion of people in the active and control CBM groups who have started counselling/psychotherapy since the baseline assessment, as well as those who discontinued counselling/psychotherapy.

These data will be collected as part of a self-report questionnaire over the internet before the first CBM session of the relevant week (8, 26 and 52).
Timepoint [2] 305789 0
Weeks 8, 26 and 52
Secondary outcome [3] 305790 0
Change in PHQ-9 total score
Timepoint [3] 305790 0
Weeks 6, 11, 15, 19, 23, 27, 36, 44, 52.
Secondary outcome [4] 305791 0
Change in attentional bias.

Attentional bias to negative stimuli will be indexed by degree of speeding to discriminate identity of probes in the area of negative rather than non-negative stimuli.
Timepoint [4] 305791 0
Weeks 6, 11, 27 and 52.
Secondary outcome [5] 305826 0
Change in interpretation bias.

Interpretive bias favouring negative resolution of ambiguity will be indexed by degree of speeding to solve word fragments related to negative rather than non-negative meanings of preceding ambiguity.
Timepoint [5] 305826 0
Weeks 6, 11, 27 and 52.

Eligibility
Key inclusion criteria
- Patient Health Questionnaire (PHQ-9) total score between 5 and 14 (inclusive)
- Age 45 years or over
- Fluent in written and spoken English
- Easy daily access to a computer with internet connection
Minimum age
45 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Current major depressive episode according to DSM-V criteria
- Past diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder
- Past clinical history of stroke or of neurodegenerative diseases (e.g., Parkinson's disease)
- Evidence of harmful or hazardous consumption of alcohol (Alcohol Unit Disorders Identification Test - AUDIT = 15)
- Evidence of cognitive impairment (Modified Telephone Interview for Cognitive Status, TICSm < 27)
- Severe visual impairment that compromises ability to read
- Severe medical illness that may compromise ongoing participation in the study for 12 months (e.g., metastatic cancer)
- No general practitioner
- No written informed consent

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
We will use the electoral roll of WA to approach a random sample of adults aged 45 years or over. They will be advised about the aims of the study and will be invited to complete a brief questionnaire to determine eligibility. Those who screen positive will undergo a subsequent interview over the phone to confirm eligibility, and those deemed eligible will receive a username and password to access the study website. A computer-generated table of random numbers derived from random blocks ranging in size will assign participants to the active or control interventions. The random list of numbers will be generated and maintained centrally by the Centre for Software Practice of the University of Western Australia. The allocation of participants to the active or control CBM will be done automatically by the computer, which will link study identification numbers (which users require to log into the study website) to either the active or control groups. Participants will not be advised of their group assignment, nor will any of the investigators. The study code will be broken only once all data points from the last participant in the study have been collected and the data analysed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated table of random numbers derived from random blocks ranging in size will assign participants to the active or control interventions. The random list of numbers will be generated and maintained centrally by the Centre for Software Practice of the University of Western Australia.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

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
We will use means and standard deviations to describe continuous variables with normal distribution, medians and inter-quartile ranges for ranked variables, and frequency tables for categorical variables. We will evaluate the primary endpoint of the study by considering the proportion of participants showing evidence of clinically significant depression (PHQ-9 equal or greater than 15 or major depression) during follow up. We will analyse the data as panel data and will include all available information in the analysis (intention-to-treat). We will use mixed models (xtmixed) to estimate changes in PHQ-9 scores over time. We have not planned interim analyses because the intervention is safe and participation is limited in time. Alpha will be set at 5% or less and 95% confidence intervals will be calculated for effect estimates. We will use xtlogit to analyses other secondary endpoints.

Currently available data show that about 10% of adults with subsyndromal symptoms of depression will develop a major depressive episode over the following 12 months. We anticipate that CBM will be associated with an absolute risk reduction of major depression of 5% over this period of time and that 15% of participants will be lost during follow up. Consequently, we will aim to recruit 510 adults (255 in each treatment arm) with subsyndromal symptoms of depression into the study (80 of whom are expected to be lost at random during follow up).

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 288357 0
University
Name [1] 288357 0
University of Western Australia
Address [1] 288357 0
35 Stirling Highway, Crawley, WA 6009
Country [1] 288357 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Stirling Highway, Crawley, WA 6009
Country
Australia
Secondary sponsor category [1] 287064 0
Hospital
Name [1] 287064 0
Royal Perth Hospital
Address [1] 287064 0
48 Murray St, Perth, WA 6000
Country [1] 287064 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290238 0
UWA Human Research Ethics Committee
Ethics committee address [1] 290238 0
35 Stirling Highway, Crawley, WA 6009
Ethics committee country [1] 290238 0
Australia
Date submitted for ethics approval [1] 290238 0
Approval date [1] 290238 0
15/08/2013
Ethics approval number [1] 290238 0
RA/4/1/6134

Summary
Brief summary
Previous research has found that people with subsyndromal depression, (those who have symptoms of depression but do not meet criteria for clinical depression), are significantly more likely to develop clinical depression within one year compared to those without subsyndromal depression. Research has shown that Cognitive Behavioural Therapy (CBT) is the most successful psychological intervention to treat depression to date. The theory behind CBT for depression suggests that depressed people have more difficulty than non-depressed people keeping their attention away from negative stimuli and are also more likely to interpret vague and unclear stimuli in a negative way. Research has shown that people at risk of developing depression, including those with subsyndromal depression, also seem to display this attentional bias to negative information.

Cognitive Bias Modification (CBM) is a relatively new therapeutic technique that aims to shift dysfunctional biased beliefs through using a computer based program. Recent research using the CBM approach has been promising in reducing symptoms of depression. However it is unknown how effective CBM is in preventing clinical depression from developing in those with subsyndromal depression.

Therefore this study aims to determine if CBM decreases the 1-year onset of a major depressive episode among adults with subsyndromal depression.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44646 0
Prof Osvaldo P. Almeida
Address 44646 0
School of Psychiatry
University of Western Australia
35 Stirling Highway
Crawley, WA 6009
Country 44646 0
Australia
Phone 44646 0
+61 8 9224 2855
Fax 44646 0
Email 44646 0
osvaldo.almeida@uwa.edu.au
Contact person for public queries
Name 44647 0
Mrs Varsha Hirani
Address 44647 0
School of Psychiatry
University of Western Australia
35 Stirling Highway
Crawley, WA 6009
Country 44647 0
Australia
Phone 44647 0
+61 8 9224 2855
Fax 44647 0
Email 44647 0
varsha.hirani@uwa.edu.au
Contact person for scientific queries
Name 44648 0
Prof Osvaldo P. Almeida
Address 44648 0
School of Psychiatry
University of Western Australia
35 Stirling Highway
Crawley, WA 6009
Country 44648 0
Australia
Phone 44648 0
+61 8 9224 2855
Fax 44648 0
Email 44648 0
osvaldo.almeida@uwa.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary