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Trial registered on ANZCTR


Registration number
ACTRN12617000899347
Ethics application status
Approved
Date submitted
15/06/2017
Date registered
19/06/2017
Date last updated
11/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Cognitive and emotional recovery training for depression (CERT-D).

Scientific title
Efficacy of Cognitive and emotional recovery training for depression (CERT-D).

Secondary ID [1] 292192 0
Nil known
Universal Trial Number (UTN)
U1111-1197-9507
Trial acronym
CERT-D (Cognitive and emotional recovery training for depression)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 303671 0
Condition category
Condition code
Mental Health 303054 303054 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All components of the intervention will take place at the clinical research facility (CRF) in the Adelaide Health and Medical Sciences building, North Terrace, Adelaide, South Australia. The intervention program will occur over 8 weeks, with 2x1hour intervention sessions per week (16hrs total). The intervention will involve training tasks targeting cognitive, emotional and social cognitive ability. Half of the participants will complete a personalised treatment, while the other half complete a standard (i.e., non-personalised) treatment. Personalised treatments will be tailored around individuals' baseline deficits, with more treatment sessions devoted to dysfunctional domains. Baseline performance will be evaluated with tests of cognition (i.e., the THINC-it tool), emotion (i.e., the PANAS) and social cognitive (i.e., the WAIS-IV-ACS-SCT), which will indicate which domains are significantly impaired (i.e., .5 SDs below the norm). In contrast, standard treatment will be the same regardless of observed baseline deficits.

Each treatment session will be devoted to a particular domain (i.e., cognition, emotion, social cognition). Cognition sessions will focus on "cold" cognitive tasks (e.g., Card sorting, Tower of London, Mental rotation). Emotion sessions will involve emotion processing and memory tasks (e.g., emotional word list memory, memory for facial affect). Social cognition sessions will involve discrimination of social cues and theory of mind tasks (e.g., "reading the mind in the eyes", Happe's Strange stories). Treatment sessions will be administered to participants individually and face to face with the researcher. Some tasks will be completed with pen and paper, while others will be completed on a computer.

The intervention will be delivered by Mr Matthew Knight. Mr Knight has submitted a PhD in experimental cognitive psychology and has experience testing, recording and analysing cognitive performance. Mr Knight will be supervised by Prof Bernhard Baune who has extensive clinical and research experience in mood disorders and cognitive dysfunction disorders obtained over many years. Prof Baune has expertise with clinical interviews, neuropsychological assessments, specimen collection and self-report questionnaires. Prior to involvement in the intervention Mr knight will undergo additional training in these
areas.

At 4 weeks (mid-RCT) subjects' performance will be assessed. Participants will be withdrawn from treatment if depression symptom severity has worsened significantly relative to baseline (i.e., greater than or equal to 20% increase in MADRS score). If this occurs, withdrawn subjects will be referred to their treating psychiatrist or GP.

Treatment adherence will be monitored by recording whether participants attend the required sessions (2 per week), and whether participants complete the entire 8 week intervention.

Intervention code [1] 298350 0
Rehabilitation
Intervention code [2] 298351 0
Treatment: Other
Comparator / control treatment
The personalised intervention group will be compared to a standard (non-personalised) intervention group. The standard intervention group will receive the same intervention regardless of individuals' baseline deficits.

A "no intervention" control group will not be recruited for the proposed study. However statistical comparisons are justified with an observational study (The CoFaMS) by the Baune group which measured similar outcomes.

See:
Baune, B. T., & Air, T. (2016). Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder–Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study). Frontiers in Psychiatry, 7.
Control group
Active

Outcomes
Primary outcome [1] 302434 0
Psychosocial Function as measured by the Functional Assessment Short Test (FAST). Specifically, change in FAST score.
Timepoint [1] 302434 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT

The primary comparison of interest will be between the pre-intervention baseline and 8 week (end of RCT) assessments. In addition, longevity of treatment effects will be assessed by comparing psychosocial function at the observation period baseline (1 week post RCT) to 3 and 6 months post-RCT.
Secondary outcome [1] 335976 0
Subdomains of Psychosocial function measured by the FAST.
These include autonomy, occupational functioning, financial issues, interpersonal relationships and leisure time. Outcome is change in subdomain score.
Timepoint [1] 335976 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT
Secondary outcome [2] 335977 0
Psychosocial Function as measured by the Functional Assessment Short Test (FAST). Specifically, total change in FAST score over entire intervention period.
Timepoint [2] 335977 0
2 Time points:

Pre-intervention baseline, 6 months post-RCT
Secondary outcome [3] 335978 0
Change in occupational functioning as measured by two scales:
Endicott Work Productivity Scale (EWPS)
Work Productivity and Activity Impairment Questionnaire (WPAI).

The EWPS will measure general occupational functioning/productivity.
The WPAI will measure the effect of cognitive, emotional and social cognition issues on occupational function.
Timepoint [3] 335978 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT
Secondary outcome [4] 335979 0
Change in resilience score, as measured by "The Resilience Scale" (Wagnild, 2009)
Timepoint [4] 335979 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT
Secondary outcome [5] 335980 0
Change in functional disability as measures by the Sheehan Disability Scale.
Timepoint [5] 335980 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT
Secondary outcome [6] 335981 0
Change in self reported cognitive failures, as reported by the cognitive failures questionnaire (CFQ).
Timepoint [6] 335981 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT
Secondary outcome [7] 335982 0
Change in depression symptom severity as measured by the Montgomery Asberg Depression Rating Scale (MADRS).
Timepoint [7] 335982 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT
Secondary outcome [8] 335983 0
Relative effect of personalised treatment vs. standard (non-personalised) treatment on psychosocial function (i.e., FAST scores).
Timepoint [8] 335983 0
6 Time points:

Pre-intervention baseline, 4 weeks post commencement of intervention (mid RCT), 8 weeks post commencement of intervention (End of RCT), Observation period baseline (1 week post-RCT), 3 months post-RCT, 6 months post-RCT
Secondary outcome [9] 335984 0
Evaluate presence of associations between serum biomarkers (e.g., TNF, IL-1, Il-6, and IL-8, BDNF, other neurotrophic factors, Monoamines) and psychosocial function and cognitive peformance.

This is a composite outcome of several biomarkers associated with psyschosocial function and cognitive performance.

Psychosocial function will be assessed with the functioning assessment short test (FAST).
Cognitive performance will be assessed with the THINC-it tool.
Timepoint [9] 335984 0
3 Time points:

Pre-intervention baseline, 8 weeks (end of RCT), 6 months post-RCT
Secondary outcome [10] 335985 0
Test of mediation: Does cognitive, emotional, or social cognitive performance mediate the effect of treatment on psychosocial performance?

This is a composite outcome which will examine the proportion of the effect of treatment (CERT-D intervention, no intervention (CoFaMS)) on psychosocial function explained by the combination of cognitive, emotional and social cognitive performance. Assuming mediation is significant, followup analyses will examine the individual contribution of cognition, emotion and social cognition to this relationship.

Cognitive function will be assessed with the THINC-it tool, emotional state with the Positive and Negative Affect Schedule (PANAS) and social cognition with the WAIS-IV Advanced Clinical Solutions social cognition test. Psychosocial functioning will be assessed with the Functional Assessment Short Test (FAST).
Timepoint [10] 335985 0
8 Weeks (end of RCT)

Eligibility
Key inclusion criteria
1. Participants have current or remitted MDD, as confirmed by the MINI Neuropsychiatric Diagnostic Interview.
2. Depression symptom severity in current MDD participants demonstrated as clinically significant (greater than or equal to 15) according to the Structured Interview Guide of the Hamilton Anxiety and Depression Scale (SIGH-AD).
3. Depression symptom severity demonstrated as mild (7-12), mild-moderate (13-19), or moderate (20-30) according the Montgomery Asberg Depression Rating Scale (MADRS) (Svanborg & Asberg, 2001).
4. Participants must be between 18 and 80 years of age.
5. Participants must be willing and able to complete digital treatment tasks presented on a computer.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current alcohol and / or substance use disorder.
2. Current diagnosis of Bipolar or Anxiety disorder.
3. Depression symptom severity demonstrated as severe (31+) according the Montgomery Asberg Depression Rating Scale (MADRS).
4. Previous diagnosis of or identified through screening with schizophrenia, a learning disorder, eating disorder, or a Pervasive Developmental Disorder (e.g., autism spectrum disorder).
5. Brain injury or impairment which could affect cognitive function (e.g., neurodevelopmental disorders, dementia)
6. Participants will be withdrawn from the study if they have subsequent severe brain/head injury; develop dementia; develop psychosis; or develop neurological conditions such as Multiple Sclerosis or Parkinson’s Disease.
7. Unable to complete questionnaires in written English

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)
Central randomisation with a computer program
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The effect size provided in the power calculation below refers to the primary outcome variable; psychosocial functioning (as measured by the “The Functioning Assessment Short Test” (FAST))

Given a sample size of 100 and an expected effect size of d = .5 for the effect of the intervention on FAST score at 8 weeks (i.e., end of RCT) relative to baseline, the study would achieve statistical power of approximately 89% (1-ß = 89) (Faul, Erdfelder, Lang, & Buchner, 2007). The rationale for this “medium” effect size is that previous interventions have found positive outcomes approximate to this magnitude (Iacoviello et al., 2014; Elgamal et al., 2007), for example in cognitive functioning.

Within subjects ANOVAs will be used for analyses comparing baseline performance to performance at 8 weeks (end of RCT). The same analyses will also evaluate any change in performance in the 6 month observational (post-RCT) period)

A paired samples t-test will evaluate whether psychosocial function differs between baseline (pre intervention) and 6 months post RCT.

A mixed ANOVA will be used with time as within subjects and intervention type (personalised, standard) as between-subjects. Psychosocial functioning (i.e., FAST score) will be the dependent variable. This analysis will evaluate whether change in psychosocial function score over time differs between the personalised intervention and standard intervention groups.

Regression analyses will be employed to evaluate whether biomarker expression is related to cognition (i.e., THINC-it performance) or psychosocial performance.

Stepwise linear regression analyses will be used to evaluate a mediation hypothesis.


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)
SA
Recruitment hospital [1] 8355 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 8361 0
Glenside Campus - Glenside
Recruitment hospital [3] 8373 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [4] 8374 0
North Eastern Community Hospital Inc - Campbelltown
Recruitment hospital [5] 8375 0
Western Hospital - Henley Beach - Henley Beach
Recruitment hospital [6] 8376 0
Modbury Hospital - Modbury
Recruitment postcode(s) [1] 16427 0
5000 - Adelaide
Recruitment postcode(s) [2] 16432 0
5065 - Glenside
Recruitment postcode(s) [3] 16440 0
5011 - Woodville
Recruitment postcode(s) [4] 16441 0
5074 - Campbelltown
Recruitment postcode(s) [5] 16442 0
5022 - Henley Beach
Recruitment postcode(s) [6] 16443 0
5092 - Modbury

Funding & Sponsors
Funding source category [1] 296729 0
University
Name [1] 296729 0
The University of Adelaide
Address [1] 296729 0
Adelaide SA 5005
Country [1] 296729 0
Australia
Funding source category [2] 296754 0
Charities/Societies/Foundations
Name [2] 296754 0
James and Diana Ramsay Foundation
Address [2] 296754 0
912/147 Pirie St, Adelaide SA 5000
Country [2] 296754 0
Australia
Primary sponsor type
Individual
Name
Prof Bernhard Baune
Address
The University of Adelaide
Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 295730 0
None
Name [1] 295730 0
Address [1] 295730 0
Country [1] 295730 0
Other collaborator category [1] 279603 0
Individual
Name [1] 279603 0
Mr Matthew Knight
Address [1] 279603 0
The University of Adelaide
Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA
Country [1] 279603 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297957 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 297957 0
North Terrace, Adelaide SA 5000
Ethics committee country [1] 297957 0
Australia
Date submitted for ethics approval [1] 297957 0
18/06/2017
Approval date [1] 297957 0
01/08/2017
Ethics approval number [1] 297957 0
R20170611
Ethics committee name [2] 297970 0
The University of Adelaide Human Research Ethics Committee
Ethics committee address [2] 297970 0
Adelaide SA 5005
Ethics committee country [2] 297970 0
Australia
Date submitted for ethics approval [2] 297970 0
20/07/2017
Approval date [2] 297970 0
Ethics approval number [2] 297970 0

Summary
Brief summary
The primary purpose of this study is to evaluate the clinical efficacy of a treatment designed to improve psychosocial function in depressed individuals. The proposed study assumes that cognitive, emotional and social cognitive impairments underlie (i.e., cause) psychosocial dysfunction. Accordingly, the proposed study will target functioning in these domains by administering repeated cognitive, emotional and social cognitive treatment tasks. Overall, the study consists of an 8 week RCT and an observational 6 months post-RCT follow-up phase. As primary outcome, we expect that psychosocial function (as measured by the FAST) will be improved at 8 weeks (end of RCT) relative to baseline, and that this improvement will be retained over a 6 month observational period. In addition, the effect of treatment on resilience, occupational functioning, functional disability, cognitive failures and depression symptom severity will also be measured. Also of interest is whether serum biomarkers related to cognition and psychosocial function are sensitive to treatment, as there is little research in this area.

It is possible that personalising treatment by individuals’ baseline impairments will lead to more effective treatment outcomes. To this end, half of the participants will complete a personalised treatment while the other half complete a standard (i.e., non-personalised treatment). Although we expect that the personalised treatment arm will result in greater improvement than the standard treatment arm, we expect clinical improvements of patients in both treatment arms during the RCT phase.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1793 1793 0 0
Attachments [2] 1794 1794 0 0

Contacts
Principal investigator
Name 75574 0
Prof Bernhard Baune
Address 75574 0
The University of Adelaide
The Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA
Country 75574 0
Australia
Phone 75574 0
+61 8 8313 7382
Fax 75574 0
Email 75574 0
bernhard.baune@adelaide.edu.au
Contact person for public queries
Name 75575 0
Prof Bernhard Baune
Address 75575 0
The University of Adelaide
The Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA
Country 75575 0
Australia
Phone 75575 0
+61 8 8313 7382
Fax 75575 0
Email 75575 0
bernhard.baune@adelaide.edu.au
Contact person for scientific queries
Name 75576 0
Prof Bernhard Baune
Address 75576 0
The University of Adelaide
The Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA
Country 75576 0
Australia
Phone 75576 0
+61 8 8313 7382
Fax 75576 0
Email 75576 0
bernhard.baune@adelaide.edu.au

No data has been provided for results reporting
Summary results
Not applicable