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Trial registered on ANZCTR


Registration number
ACTRN12616000778482
Ethics application status
Approved
Date submitted
8/06/2016
Date registered
15/06/2016
Date last updated
6/02/2019
Date data sharing statement initially provided
6/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
RAndomised trial aiming to imProve the quality of lIfe of people with Dementia (Alzheimer's disease) plus their carers (RAPID-Plus).
Scientific title
Randomised trial aiming to improve the quality of life of people with dementia (Alzheimer's disease) plus their carers through a novel Cognitive Bias Modification intervention.
Secondary ID [1] 289400 0
None
Universal Trial Number (UTN)
Trial acronym
RAPID-Plus
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 299068 0
Alzheimer's disease 299079 0
Condition category
Condition code
Mental Health 299103 299103 0 0
Depression
Neurological 299104 299104 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cognitive bias modification (CBM) is a novel, simple, and safe computer-based intervention that requires behavioural responses from participants (i.e., pressing one of two buttons). CBM specifically targets attentional and interpretative biases associated with anxiety, dysphoria, and depression. CBM operates through implicit learning systems.

In this trial two forms of CBM will comprise the intervention, CBM-A (attentional modification) and CBM-I (interpretive modification).

During CBM-A participants will be repeatedly exposed to pairs of emotional faces. Each face pair includes one face displaying a negative emotion, and one face portraying a non-negative emotion. The presentation of each face pair lasts 500 ms. After each face pair has been presented, a probe is presented in the same spatial position where one of the faces was located. Participants are asked to indicate the shape of each probe by pressing a square or a circle on a response box. The time taken for participants to discriminate the identity of the probe is recorded. In the active CBM-A condition, designed to reduce attention to negative information, and expected to result in subsequent reduction in symptoms of depression, probes always appear in the position of non-negative faces.

During CBM-I, participants will be repeatedly exposed to single ambiguous words (e.g. 'cane') for 1000 ms on the computer screen, followed by a pair of words. In each word pair, one word will be semantically related to either a negative or benign meaning (e.g. 'hit' or 'furniture') of the cue word, and one semantically unrelated word (e.g. 'cloud'). Participants will be asked to indicate whether the semantically related word appeared on the left or right side of the computer screen by pressing the left or right button on a response box. The time taken for participants to discriminate the location of the semantically related word is recorded. In the active CBM-I condition, designed to reduce negative interpretation of ambiguous information, and expected to result in subsequent reduction in symptoms of depression, the semantically related word will always present a benign meaning.

In this trial, each CBM session will last approximately 30 minutes: 15 minutes each for CBM-A and CBM-I. Over the course of the trial the CBM sessions will take place during office hours as follows: Week 1 – daily, Week 2 - 3 times, Weeks 3 to 12 – fortnightly, Weeks 13 to 26 – monthly (total of 16 sessions over 6 months). The CBM sessions will be delivered on a local PC station at the study centre under supervision of a trained research officer. The first session will also comprise initial baseline assessment of primary and secondary outcome measures.

Intervention code [1] 294985 0
Treatment: Other
Intervention code [2] 294996 0
Behaviour
Comparator / control treatment
The control condition will follow the same procedure as described for the active intervention group, except for the following minor changes. During the CBM-A control condition, probes will appear with equal frequency in the location of non-negative and negative faces. During the CBM-I control condition, the semantically related words will portray a benign or negative meaning with equal frequency.
Control group
Placebo

Outcomes
Primary outcome [1] 298570 0
A primary outcome of interest is the change, from baseline assessment, in severity depressive symptoms in patients with Alzheimer's disease (AD).

The Cornell Scale for Depression in Dementia (CSDD) will be used to measure severity of depressive symptoms at baseline, and measure change in severity of symptoms.
Timepoint [1] 298570 0
12 weeks after baseline assessment.
Primary outcome [2] 298571 0
A primary outcome of interest is the change, from baseline assessment, in severity depressive symptoms in carers of patients with Alzheimer's disease.

The Patient Health Questionnaire (PHQ-9) will be used to measure severity of depressive symptoms at baseline, and measure change in severity of symptoms.
Timepoint [2] 298571 0
12 weeks after baseline assessment.
Primary outcome [3] 298572 0
A primary outcome of interest is the change, from baseline assessment, in quality of life of patients with Alzheimer's disease.

The Quality of Life - Alzheimer's Dementia Scale (QoL-AD) will be used to measure quality of life at baseline, and measure change in quality of life.
Timepoint [3] 298572 0
12 weeks after baseline assessment.

Secondary outcome [1] 324609 0
A secondary outcome measure will be change, from baseline assessment, in severity of depressive symptoms in patients with Alzheimer's disease. This outcome reflects assessment of change in depressive symptoms after a period longer than that of the primary outcome above.

The CSDD will be used to measure severity of depressive symptoms at this time point.

Timepoint [1] 324609 0
26 weeks after baseline assessment.
Secondary outcome [2] 324610 0
A secondary outcome measure will be incidence of major depression in patients with Alzheimer's disease.

Incidence of major depression will be determined by a CSDD score of greater than 10 at this time point, and subsequent confirmation by a clinician using the Structured Interview for Depression in Alzheimer's disease and resulting in a diagnosis according to National Institute of Mental Health provisional diagnostic criteria for depression in Alzheimer's disease.
Timepoint [2] 324610 0
26 weeks after baseline assessment.
Secondary outcome [3] 324611 0
A secondary outcome measure will be change, from baseline assessment, in burden of care as reported by carers.

Burden of care will be measured by the 12-item Zarit Burden Interview (ZBI).
Timepoint [3] 324611 0
12 weeks after baseline assessment, and 26 weeks after baseline assessment.
Secondary outcome [4] 324639 0
A secondary outcome measure will be change, from baseline assessment, in level of attentional bias and interpretive bias, across the duration of the trial.

This will be assessed via a baseline assessment of attentional bias and interpretive bias prior to CBM intervention at the initial session, with assessments repeated throughout the duration of the trial. Assessment of attentional bias and interpretive bias will be conducted using computer tasks designed specifically for this study, which will reflect methodologies typically employed for assessment of such biases.
Timepoint [4] 324639 0
12 weeks after baseline assessment, and 26 weeks after baseline assessment.
Secondary outcome [5] 324713 0
A secondary outcome measure will be change, from baseline assessment, in severity of depressive symptoms in carers. This outcome reflects assessment of change in depressive symptoms after a period longer than that of the primary outcome above.

The Patient Health Questionnaire (PHQ-9) will be used to measure severity of symptoms at this time point.

Timepoint [5] 324713 0
26 weeks after baseline assessment.
Secondary outcome [6] 324714 0
A secondary outcome measure will be incidence of major depression in carers

Carers scoring equal to or greater than 10 on the PHQ-9 at this time point will be assessed by a study clinician. Incidence of major depression will be determined by the clinician according to DSM 5 criteria.
Timepoint [6] 324714 0
26 weeks after baseline assessment.

Eligibility
Key inclusion criteria
The inclusion criteria will be:
For AD participants
* Diagnosis of major neurocognitive disorder due to probable AD
according to DSM-5 criteria
* Mini-mental State Examination (MMSE) score of greater than or equal to 15
* Cornell Scale for Depression in Dementia (CSDD) score greater than or equal to 4
* Availability of a carer willing to participate in the trial
* Fluent in written and spoken English

For Carers, we will include those who:
* Are aged greater than or equal to 18 years
* Are fluent in written and spoken English
* Are free of diseases likely to undermine ongoing participation in the
study for 24 months (e.g., metastatic cancer)
* Do not consume alcohol in excess of 14 standard drinks per week
* Show no evidence of cognitive impairment (MMSE greater than or equal to 24/30)
* Do not meet DSM-5 criteria for major depression
* Show no evidence of active suicidal intent
* Show no evidence of visual impairment that might compromise ability to read or use the computer
* Are registered with a general practitioner
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
We will exclude individuals who:
* Meet National Institute of Mental Health criteria for depression in AD
* Have medical conditions that are likely to compromise their ability to
complete the required activities of the study e.g. severe sensory
impairment or life expectancy of < 2 years from time of enrolment
* Consume alcohol in excess of 14 standard drinks per week
* Have no health practitioner who can provide ongoing clinical care
* Decline or are unable to provide informed consent

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)
Eligible participants will be automatically assigned to one of the two CBM conditions (active/control) 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 CBM conditions (active/control) according to a list of random numbers generated by a computer. 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 or research staff will be aware of the randomisation code.
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

Recruitment
Recruitment status
Recruiting
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,VIC
Recruitment hospital [1] 5939 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 5940 0
Bentley Health Service - Bentley
Recruitment hospital [3] 5941 0
Osborne Park Hospital - Stirling
Recruitment hospital [4] 5942 0
Fremantle Hospital and Health Service - Fremantle
Recruitment hospital [5] 5943 0
Armadale Kelmscott Memorial Hospital - Armadale
Recruitment hospital [6] 5944 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [7] 5946 0
St Vincent's Private Hospital - Fitzroy
Recruitment hospital [8] 5947 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [9] 5948 0
Monash Medical Centre - Clayton campus - Clayton

Funding & Sponsors
Funding source category [1] 298724 0
Other Collaborative groups
Name [1] 298724 0
Dementia Collaborative Research Centres
Address [1] 298724 0
Queensland University of Technology
Office of Commercial Services
88 Musk Ave, Lvl 4
Kelvin Grove, QLD 4059
Country [1] 298724 0
Australia
Primary sponsor type
Other
Name
WA Centre for Health and Ageing
Address
Level 6
48 Murray St
Perth, WA, 6000
Country
Australia
Secondary sponsor category [1] 292604 0
None
Name [1] 292604 0
Address [1] 292604 0
Country [1] 292604 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295213 0
South Metropolitan Area Health Service Human Research Ethics Committee (EC00265)
Ethics committee address [1] 295213 0
Ethics committee country [1] 295213 0
Australia
Date submitted for ethics approval [1] 295213 0
15/06/2016
Approval date [1] 295213 0
12/07/2016
Ethics approval number [1] 295213 0
2016-126
Ethics committee name [2] 295214 0
St Vincent's Hospital (Melbourne) HREC (EC00343)
Ethics committee address [2] 295214 0
Ethics committee country [2] 295214 0
Australia
Date submitted for ethics approval [2] 295214 0
15/06/2016
Approval date [2] 295214 0
Ethics approval number [2] 295214 0
Ethics committee name [3] 295215 0
Monash University Research Ethics Committee (EC00234)
Ethics committee address [3] 295215 0
Ethics committee country [3] 295215 0
Australia
Date submitted for ethics approval [3] 295215 0
15/06/2016
Approval date [3] 295215 0
Ethics approval number [3] 295215 0

Summary
Brief summary
Depression is common in people with Alzheimer’s disease (AD) and their carers and is a frequent cause of distress and reduced quality of life (QoL). Pharmacological treatment is modestly effective in treating major depression, although this is largely ineffective in those with milder depression (subsyndromal depression - SSD) and in people with dementia ,and is frequently associated with unacceptable side effects. It is therefore essential that we are able to identify safe and easily accessible therapies for these debilitating symptoms.
Cognitive bias modification (CBM) is a simple, novel and safe intervention that targets attentional and interpretative biases associated with anxiety and depression. CBM has been shown to be effective in reducing depressive symptoms in younger adults but studies in people with cognitive impairment and their carers are lacking. Our preliminary research has indicated that CBM is well tolerated by people with AD and could be easily accessed at home, making it a potentially invaluable intervention for depression in this population.
The aims of this study are to determine; The effect of CBM in reducing the severity of depressive symptoms in AD, the effect of CBM in improving mood in carers of people with AD, and the effect of CBM on QOL of people with AD and their carers. People with AD and their carers (dyads) will be randomly assigned to an active or control CBM intervention in a 2 x 2 double-blind, parallel design. The intervention will be conducted over 6 months. For AD participants and carers, change in severity of depressive symptoms, and change in QoL, after 12 weeks, will be outcomes of primary interest. For AD participants and carers, change in severity of depressive symptoms after completion of treatment at 26 weeks, and incidence of major depression at 6 months, will be secondary outcomes of interest. Burden of care as reported by carers at 12 and 26 weeks will also be a secondary outcome of interest.
Dementia is a common condition and is frequently associated with a diverse range of neuropsychiatric symptoms, including depression and anxiety. Our current understanding of the cause and management of these symptoms is far from optimal. The proposed study trials a simple and safe treatment that could be easily implemented into everyday clinical practice. This study will provide high quality evidence for the efficacy of CBM in improving the quality of lives of people with AD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66538 0
Dr Andrew Ford
Address 66538 0
WA Centre for Health & Ageing (M577)
University of Western Australia
35 Stirling Highway
Perth WA 6009 Australia
Country 66538 0
Australia
Phone 66538 0
+61 8 9224 0295
Fax 66538 0
Email 66538 0
andrew.ford@uwa.edu.au
Contact person for public queries
Name 66539 0
Ms Varsha Hirani
Address 66539 0
WA Centre for Health & Ageing (M577)
University of Western Australia
35 Stirling Highway
Perth WA 6009 Australia
Country 66539 0
Australia
Phone 66539 0
+61 8 9224 0295
Fax 66539 0
Email 66539 0
varsha.hirani@uwa.edu.au
Contact person for scientific queries
Name 66540 0
Dr Andrew Ford
Address 66540 0
WA Centre for Health & Ageing (M577)
University of Western Australia
35 Stirling Highway
Perth WA 6009 Australia
Country 66540 0
Australia
Phone 66540 0
+61 8 9224 0295
Fax 66540 0
Email 66540 0
andrew.ford@uwa.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
No Results