Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000420640
Ethics application status
Approved
Date submitted
11/04/2014
Date registered
16/04/2014
Date last updated
11/02/2021
Date data sharing statement initially provided
11/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
RAndomised controlled trial to imProve depressIon and the quality of life of people with Dementia using cognitive bias modification (RAPID)
Scientific title
RAndomised controlled trial to imProve depressIon and the quality of life of people with Dementia using cognitive bias modification (RAPID)
Secondary ID [1] 284428 0
Nil
Universal Trial Number (UTN)
Trial acronym
RAPID
Linked study record

Health condition
Health condition(s) or problem(s) studied:
depression
 291630 0
Alzheimer's disease 291631 0
Condition category
Condition code
Mental Health 292010 292010 0 0
Depression
Neurological 292011 292011 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be asked to attend the WA Centre for Health and Ageing, Royal Perth Hospital, on a daily basis for a total of 10 sessions of cognitive bias modification (CBM) (2 weeks – excluding weekends). Each session will be delivered on a 24’’ high-resolution screen using a local PC station, and will last approximately 30 minutes: 15 minutes each for CBM-Attention (CBM-A) and for CBM-Interpretation (CBM-I).

In the CBM-A session, participants will be shown pairs of emotionally discrepant photos for 500 ms (sad or neutral/happy faces). Each pair will then be replaced by a small probe (square or circle) appearing in the screen position previously occupied by one of the photos. Participants will be instructed to use a response box with a square and a round button to indicate the shape of the probe that appeared on the screen. The probe will then disappear and will be replaced, after 1 second, by another pair of photos to initiate the next trial. The time to discriminate probe identity (square or circle) will be recorded automatically. In the active CBM condition, designed to reduce attention to negative information, probes will always appear in the position of neutral/happy faces.

In the interpretative CBM sessions (CBM-I), single ambiguous cue-words that permit a negative and benign interpretation (e.g., BEAT) will first appear in the top half of the screen for 1s. Then two words will appear on the bottom half of the screen: one on the left and the other on the right hand side. This word-pair will consist of one target word that is semantically related either to the negative or benign meaning of the ambiguous cue-word (e.g., VICTORY or PUNISH), and one word that is unrelated to either meaning of the ambiguous cue-word (e.g., CLOUD). Participants will be asked to identify which is the target word and use the response box to indicate whether the semantically-related word appeared on the left or right-hand side of the screen (by pressing the left or the right hand side button on the response box, respectively). The time required to accurately identify the target word will be recorded automatically. In the active CBM condition, designed to reduce negative interpretations of ambiguity, target words always will be associated with the benign meanings of the cue-words, discouraging their negative interpretation.
Intervention code [1] 289178 0
Treatment: Other
Comparator / control treatment
The comparator control intervention will follow the same procedures described for the active intervention group, except that in the CBM-A control condition the probes will appear 50% of the time in the position of neutral/happy faces and 50% of the time in the position of the sad faces. In the CBM-I control condition 50% of the target words will be associated with the benign meaning and 50% with the negative meanings of the cue-words.
Control group
Active

Outcomes
Primary outcome [1] 291902 0
We will use the Cornell Scale for Depression in Dementia (CSDD) to establish the presence of clinically significant symptoms of depression (CSDD greater or equal 8), measure changes in the severity of symptoms, and ascertain the remission of symptoms (CSDD less than 8).
Timepoint [1] 291902 0
Two weeks after the baseline assessment.
Primary outcome [2] 291903 0
The Quality of Life AD (QoL-AD) scale will be this study’s measure of quality of life. It consists of 13 items that assess behavioural competence, psychological status, physical functioning and interpersonal environment that is of relevance to older adults. Each item offers four answers that range from poor (1) to excellent (4), with the total possible score ranging from 13 to 52. Higher scores indicate better quality of life. The QoL-AD has the added advantage of offering patient and carer versions. The QoL-AD has robust psychometric propertie. Changes in QoL-AD scores from baseline represent another outcome of interest of this trial.
Timepoint [2] 291903 0
Two weeks after the baseline assessment.
Secondary outcome [1] 307778 0
Changes in CSDD scores.
Timepoint [1] 307778 0
Twelve weeks after the baseline assessment.
Secondary outcome [2] 307779 0
Changes in QoL-AD scores.
Timepoint [2] 307779 0
Twelve weeks after the baseline assessment.
Secondary outcome [3] 307780 0
Negative attentional bias will be indexed by degree of relative speeding to discriminate probes appearing in the position of sad faces compared with the happy/neutral faces.
Timepoint [3] 307780 0
Two and twelve weeks after the baseline assessment.
Secondary outcome [4] 307781 0
Negative interpretative bias will be indexed by degree of relative speeding to identify words associated with negative compared with the benign meaning of the ambiguous word.
Timepoint [4] 307781 0
Two and twelve weeks after the baseline assessment.
Secondary outcome [5] 307782 0
Change of scores on the Mini-Mental State Examination (MMSE).
Timepoint [5] 307782 0
Two and twelve weeks after the baseline assessment.

Eligibility
Key inclusion criteria
We will recruit 80 people with depression in mild to moderate severity Alzheimer’s disease according to the following inclusion criteria:
1. Diagnosis of probable AD according to NINCDS-ADRDA criteria, which is largely consistent with DSM-V diagnosis of major neurocognitive disorder due to probable AD,
2. Mini-Mental State Examination (MMSE) score equal or greater than 15,
3. Cornell Scale for Depression in Dementia (CSDD) equal or greater than 8,
4. Fluent in written and spoken English (preferred language for at least 10 years).
Minimum age
50 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
We will exclude from participation people who have:
1. One or more diseases likely to compromise ongoing participation in the trial (for example, severe visual impairment),
2. A weekly alcohol consumption greater than 28 standard drinks (> 4 drinks per day) or 6 or more standard drinks on any one day of the week,
3. Active suicidal intent,
4. No health practitioner who is able to provide ongoing clinical care,
5. Changed antidepressants during the preceding four weeks,
6. Not given informed consent to participate.

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)
We will recruit community-dwelling participants from the Perth metropolitan area who are in contact with our clinical services (including Memory Clinics and Memory Services of the Royal Perth, Bentley and Swan Hospitals). These services assess 8-10 new referrals with the diagnosis of dementia per week (about 5 or 6 with AD) and review twice as many ongoing cases. If necessary, we will contact local primary care practices and other mental health services for older adults to assist with recruitment. Volunteers who meet the study entry criteria will be asked to complete all further assessments and study procedures at the WA Centre for Health and Ageing, located at the Royal Perth Hospital.

Eligible participants will be automatically assigned to one of the two treatment groups by a computer. Allocation will be concealed from both the participant and the research team.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned to control and active CBM according to a list of random numbers generated by computer in blocks. The allocation ratio will be 1:1. Group allocation codes will then be linked to random id numbers that will be assigned to each participant when they log on for their first CBM session. Neither the participant nor research staff will be aware of the independently controlled randomisation code. Participants will be advised about the study’s aims and procedures (which will be exactly the same for all participants), but not about the details characterising the control and the active intervention. In addition, the research person supervising the CBM sessions will not be involved in the collection of any outcome data. Group assignment codes will only be open after the last endpoint of interest of the last participant in the trial is collected.
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
Study size:
Data from the placebo-controlled trial of mirtazapine and sertraline indicate that people with DAD treated with placebo improved, on average, 6 points (standard deviation, SD = 4) after 13 weeks (Banerjee et al., 2011). We estimate that people treated with CBM should improve an additional 3 points (9 in total, SD = 4). A sample size of 76 people with DAD (38 per group) would give the study 90% power to declare this difference as significant (alpha < 5%, two-tailed). We plan to recruit 80 participants with DAD (40 randomly assigned to each treatment group) and anticipate that 15% of them will be lost during the study. In this case, the trial would be completed by 68 participants and would still have 87% power. We further anticipate that loss to follow up will be minimal during the initial two weeks of treatment, although changes in scores may also be smaller at that point in time (3 points for controls and 6 for intervention participants). If we lose 10% of our sample during the initial two weeks, primary outcome data would be available for 72 participants (36 per group) and the study would have 89% power to declare as significant such a difference between the groups. Furthermore, a sample of this size would give the study 84% power to declare as significant changes in QoL-AD scores of 1 point for controls and 4.5 points for active CBM participants over three months (SD=5 for both groups; positive changes indicate expected improvement). The changes in response bias (measured in milliseconds) are expected to be associated with a minimum effect size of 0.4 (Cohen’s d)(See et al., 2009), which would require about 50 trials per participant (within group comparison). As each CBM session includes 96 trials for attention (faces) and 96 trials for interpretive bias (words), the study will have ample power to investigate this outcome.

Statistical analyses:
We will use means and standard deviations to describe continuous variables with normal distribution, medians and inter-quartile ranges for ordinal variables, and frequency tables for categorical variables. We will use t-tests to compare the change in CSDD and QoL-AD scores between baseline and week 2. If statistical adjustments are required because of unbalance in other study measures (e.g., gender distribution), we will use analysis of co-variance. We will use multilevel mixed models to analyse changes in CSDD, QoL and attentional and interpretative biases from baseline to week 2 and 12. We will investigate the interaction between group and time effects (statistical adjustments will be made, if necessary). This analysis is intention to treat. Multiple imputation (imputed chain equations) will be employed for the analysis of week 2 data, if necessary.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
2/06/2014
Actual
2/06/2014
Date of last participant enrolment
Anticipated
14/09/2020
Actual
8/07/2016
Date of last data collection
Anticipated
15/12/2020
Actual
29/09/2016
Sample size
Target
80
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 2308 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 2309 0
Bentley Health Service - Bentley
Recruitment hospital [3] 2310 0
Swan Districts Hospital - Middle Swan
Recruitment hospital [4] 2311 0
Osborne Park Hospital - Stirling
Recruitment hospital [5] 2312 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 6024 0
Royal Melbourne Hospital - City campus - Parkville

Funding & Sponsors
Funding source category [1] 289080 0
Other
Name [1] 289080 0
WA Centre for Health & Ageing
Country [1] 289080 0
Australia
Primary sponsor type
Other
Name
WA Centre for Health & Ageing
Address
MRF building, Level 6,
Rear 50 Murray street
Perth, WA 6000
Country
Australia
Secondary sponsor category [1] 287742 0
None
Name [1] 287742 0
Address [1] 287742 0
Country [1] 287742 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290870 0
Royal Perth Hospital Ethics Committee
Ethics committee address [1] 290870 0
Level 5 Colonial House
Royal Perth Hospital
GPO Box X2213
Perth, WA 6001
Ethics committee country [1] 290870 0
Australia
Date submitted for ethics approval [1] 290870 0
05/03/2014
Approval date [1] 290870 0
29/04/2014
Ethics approval number [1] 290870 0
REG 14-036

Summary
Brief summary
Depressive symptoms are common and undermine the quality of life of people with Alzheimer’s disease (AD). Cholinesterase inhibitors and antidepressants have all but no effect on the mood of patients, and their use is associated with greater risk of adverse events compared with placebo. The use of traditional psychotherapeutic interventions, such as cognitive behavioural therapy, is hindered by the presence of cognitive impairment. Cognitive bias modification (CBM) is a novel, simple and safe intervention that targets attentional and interpretative biases associated with anxiety, dysphoria and depression. CBM operates through implicit learning systems, which are spared until late in the course of the dementia illness. CBM is effective at reducing depressive symptoms in adults without cognitive impairment and our pilot data indicate that this is a feasible and, most likely, efficacious treatment for people with depression in AD (DAD). Moreover, CBM is safe and unlikely to be associated with significant adverse events in this vulnerable population. RAPID will evaluate this innovative intervention in a carefully designed trial that brings together an accomplished team of investigators with expertise in ageing research, depression, dementia, CBM, randomised trials and translation of research findings into clinical practice. This study will produce definitive high quality evidence for the benefits of CBM in improving the quality of life of people with DAD.
Trial website
Trial related presentations / publications
Almeida, O.P., MacLeod, C., Flicker, L., Ford, A.H., Grafton, B. & Etherton-Beer, C. (2014). RAndomised controlled trial to imProve depressIon and the quality of life of people with Dementia using cognitive bias modification: RAPID Study Protocol. BMJ Open, 4, e005623.
Public notes

Contacts
Principal investigator
Name 47686 0
Prof Osvaldo P. Almeida
Address 47686 0
School of Psychiatry & Clinical Neurosciences (M577) University of Western Australia 35 Stirling Highway Crawley, WA 6009
Country 47686 0
Australia
Phone 47686 0
+61-8-92240295
Fax 47686 0
Email 47686 0
[email protected]
Contact person for public queries
Name 47687 0
Ms Varsha Hirani
Address 47687 0
School of Psychiatry & Clinical Neurosciences (M577) University of Western Australia 35 Stirling Highway Crawley, WA 6009
Country 47687 0
Australia
Phone 47687 0
+61-8-92240295
Fax 47687 0
Email 47687 0
[email protected]
Contact person for scientific queries
Name 47688 0
Prof Osvaldo P. Almeida
Address 47688 0
School of Psychiatry & Clinical Neurosciences (M577) University of Western Australia 35 Stirling Highway Crawley, WA 6009
Country 47688 0
Australia
Phone 47688 0
+61-8-92240295
Fax 47688 0
Email 47688 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
study has been suspended.


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.