ANZCTR - Registration

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]

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

Condition category

Condition code

Mental Health

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]

Rehabilitation

Intervention code [2]

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]

Psychosocial Function as measured by the Functional Assessment Short Test (FAST). Specifically, change in FAST score.

Timepoint [1]

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]

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]

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]

Psychosocial Function as measured by the Functional Assessment Short Test (FAST). Specifically, total change in FAST score over entire intervention period.

Timepoint [2]

2 Time points:

Pre-intervention baseline, 6 months post-RCT

Secondary outcome [3]

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]

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]

Change in resilience score, as measured by "The Resilience Scale" (Wagnild, 2009)

Timepoint [4]

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]

Change in functional disability as measures by the Sheehan Disability Scale.

Timepoint [5]

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]

Change in self reported cognitive failures, as reported by the cognitive failures questionnaire (CFQ).

Timepoint [6]

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]

Change in depression symptom severity as measured by the Montgomery Asberg Depression Rating Scale (MADRS).

Timepoint [7]

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]

Relative effect of personalised treatment vs. standard (non-personalised) treatment on psychosocial function (i.e., FAST scores).

Timepoint [8]

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]

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]

3 Time points:

Pre-intervention baseline, 8 weeks (end of RCT), 6 months post-RCT

Secondary outcome [10]

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]

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

Sex

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

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

16/08/2017

Actual

1/09/2017

Date of last participant enrolment

Anticipated

26/12/2018

Actual

Date of last data collection

Anticipated

22/07/2019

Actual

Sample size

Target

100

Accrual to date

74

Final

Recruitment in Australia

Recruitment state(s)

SA

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [2]

Glenside Campus - Glenside

Recruitment hospital [3]

The Queen Elizabeth Hospital - Woodville

Recruitment hospital [4]

North Eastern Community Hospital Inc - Campbelltown

Recruitment hospital [5]

Western Hospital - Henley Beach - Henley Beach

Recruitment hospital [6]

Modbury Hospital - Modbury

Recruitment postcode(s) [1]

5000 - Adelaide

Recruitment postcode(s) [2]

5065 - Glenside

Recruitment postcode(s) [3]

5011 - Woodville

Recruitment postcode(s) [4]

5074 - Campbelltown

Recruitment postcode(s) [5]

5022 - Henley Beach

Recruitment postcode(s) [6]

5092 - Modbury

Funding & Sponsors

Funding source category [1]

University

Name [1]

The University of Adelaide

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

James and Diana Ramsay Foundation

Country [2]

Australia

Primary sponsor type

Individual

Name

Prof Bernhard Baune

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Other collaborator category [1]

Individual

Name [1]

Mr Matthew Knight

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital Research Ethics Committee

Ethics committee address [1]

North Terrace, Adelaide SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/06/2017

Approval date [1]

01/08/2017

Ethics approval number [1]

R20170611

Ethics committee name [2]

The University of Adelaide Human Research Ethics Committee

Ethics committee address [2]

Adelaide SA 5005

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

20/07/2017

Approval date [2]

Ethics approval number [2]

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

Public notes

Attachments [1]

/AnzctrAttachments/373129-CERT-D Ethics Protocol.docx (Protocol)

Attachments [2]

/AnzctrAttachments/373129-CERT-D Participant Information Sheet.docx (Participant information/consent)

Contacts

Principal investigator

Name

Prof Bernhard Baune

Address

The University of Adelaide
The Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA

Country

Australia

Phone

+61 8 8313 7382

Email

[email protected]

Contact person for public queries

Name

Bernhard Baune

Address

The University of Adelaide
The Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA

Country

Australia

Phone

+61 8 8313 7382

Email

[email protected]

Contact person for scientific queries

Name

Bernhard Baune

Address

The University of Adelaide
The Adelaide Medical School
Discipline of Psychiatry

57 North Terrace
Adelaide, SA 5000
AUSTRALIA

Country

Australia

Phone

+61 8 8313 7382

Email

[email protected]

Source	Title	Year of Publication	DOI
Embase	Psychological training to improve psychosocial function in patients with major depressive disorder: A randomised clinical trial.	2021	https://dx.doi.org/10.1016/j.psychres.2021.113906
Embase	Cognitive improvement in patients with major depressive disorder after personalised multi domain training in the CERT-D study.	2023	https://dx.doi.org/10.1016/j.psychres.2023.115590

Trial Review

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