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Trial registered on ANZCTR


Registration number
ACTRN12619001080112
Ethics application status
Approved
Date submitted
19/07/2019
Date registered
6/08/2019
Date last updated
6/08/2019
Date data sharing statement initially provided
6/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Enhancing Recovery in Mood Disorders with Group Cognitive Remediation and Psychotherapy
Scientific title
Enhancing Long-Term Cognitive and Functional Recovery in Adults with Mood Disorders: Group-Based Cognitive Remediation as an Adjunct to Psychotherapy
Secondary ID [1] 298489 0
None.
Universal Trial Number (UTN)
U1111-1228-6718
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bipolar disorder 313578 0
Major depressive disorder 313580 0
Condition category
Condition code
Mental Health 312012 312012 0 0
Depression
Mental Health 312013 312013 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
IPSRT was developed for Bipolar Disorder (Ellen Frank).

The three main elements of IPSRT include: 1) psychoeducation, 2) interpersonal strategies for problems in relationships (5 problem areas), and 3) behavioural strategies to stabilise routine and reduce social/circadian rhythm disruption.

IPSRT is delivered according to a manualised protocol. IPSRT begins with an assessment which includes the completion of an ‘Illness History Timeline’, and ‘Interpersonal Inventory’, and feeding back the psychological formulation to the patient within the IPSRT framework. During this phase, patients also begin completing the Social Rhythm Metric, which involves the patient documenting key social rhythms and their mood rating on a daily basis.

During the middle phase of IPSRT, patients will be working on stabilisation of their social rhythms (continuing to use the Social Rhythm Metric if appropriate), and sleep hygiene strategies will be provided as part of this. For the ‘interpersonal’ aspect of therapy, the patient and therapist collaboratively choose one or two primary interpersonal problem areas to focus on that clearly relate to the patient's mood (either: 1) Interpersonal Disputes, 2) Role Transitions, 3) Grief and Loss, 4) Interpersonal Sensitivity, and/or 5) Grief for the Lost Healthy Self). Strategies for this phase include: psychoeducation, communication analysis, relationship appraisal, expression of affect, role-play, perspective taking, assertiveness skills training, and problem-solving. Handouts for the assessment and therapy phase of treatment can be found and uploaded at https://www.ipsrt.org/.

Training of therapists involved training from the original developers of IPSRT through the University of Pittsburgh (Professor Holly Swartz), online training (https://www.ipsrt.org/), and then supervision in two training cases with an experienced IPSRT therapist.
Seven therapists will be providing IPSRT on this trial: 4x mental health nurses, 1x social worker, 2x clinical psychologists. Each patient will have one therapist for the duration of the study. All have had experience providing IPSRT in previous clinical trials.

IPSRT sessions will be between 50 to 60 minutes in duration and completed in an individual, face-to-face format. Sessions will be weekly for 12 weeks, followed by fortnightly (approximately 10 sessions), and then monthly sessions (4 sessions), making a total of about 24 sessions over the 12-month treatment period. If there is deterioration in the patient’s mood, they may be seen more regularly. Therapy will be face-to-face in an individual format. IPSRT sessions will take place in a Clinical Research Unit (Department of Psychological Medicine, University of Otago, Christchurch, NZ), in specifically designed therapy rooms.

IPSRT therapy supervision will be provided to the IPSRT therapist by an experienced IPSRT therapist on a fortnightly basis. Therapists will tape approximately 10% of their sessions in order to assess fidelity of treatment.

GROUP-BASED COGNITIVE REMEDIATION
A Cognitive Remediation (CR) intervention is being delivered in order to improve cognitive and functional outcomes in our sample with mood disorders.

The Group-Based CR intervention will be provided in the second 6-months of this 12-month treatment trial.

Materials required for treatment include a Samsung tablet for each patient, headphones, worksheets, and equipment required for simulated role-plays.

This group-based CR treatment is based on the Action-Based Cognitive Remediation (ABCR) treatment manual (Christopher Bowie, 2018). In the current study, ABCR has been adapted for the New Zealand context, and has been shortened to eight sessions in the same format. The principal investigator (KD) has been trained in this treatment approach and will lead the training of therapists in the current RCT.

Group-based CR will involve weekly, 90-minute, face-to-face sessions over 8 weeks (i.e., 8 sessions). Each group session will involve three main components:
- Practice of computerised exercises, which will be provided by Scientific Brain Training Professional (SBT-Pro; www.scientificbraintrainingpro.com).
- Coaching on strategies to improve performance
- ‘Bridging’ - use of role-play and group exercises to help transfer skills and strategies used in computerised exercises to everyday functioning.

In terms of treatment content, sessions include the following, in the same order:
- Didactic introduction: outlining the theme of the day (e.g., ‘Shifting Your Focus’).
- Skill building with computerised cognitive training: therapists will demonstrate the computer task on a large screen, then there will be about 10 minutes of computer practice. A group strategy discussion follows, and then these strategies are tested with a further 10 minute computer practice session.
- Real-world simulations: therapists will demonstrate the simulation (reminding group members about strategies from the computerised cognitive exercise) and then the group engages with the simulation.
- Cognitive activation and goal setting: a bridging discussion about how the computerised exercises and real-world simulations relate to activities in everyday life and personal goals, followed by identification of cognitively stimulating activities for homework before the next session.

Groups will be conducted in a rolling structure, so that patients will continually be starting and ending the treatment as they complete their dose of treatment. Treatment will take place in the Clinical Research Unit (Department of Psychological Medicine, University of Otago, Christchurch, NZ).

Outside of group CR sessions, patients will be expected to practise computerised exercises online every day (for at least 30 minutes), with therapists being able to provide individual online feedback. Treatment adherence can be assessed by observing online how many practice sessions each patient has completed each week, and for how many minutes.

Group therapists will consist of: 1x clinical psychologist and 3x mental health nurses, all experienced in the provision of psychological therapy. Therapists have been trained by KD in this CR intervention. A CR fidelity checklist will be completed by KD to ensure treatment is being delivered according to protocol.

MEDICATION MANAGEMENT
All patients in the study will have an initial, face-to-face session with a psychiatrist who will assess medication needs. The assessing psychiatrist will then see the patient at 6 months and 12 months to monitor response to medication. Sessions will be between 30-60 minutes in length. Patients will be seen more regularly if deemed necessary by the therapist, psychiatrist, or patient.

Psychiatrists will prescribe medication according to Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders.
Intervention code [1] 314956 0
Treatment: Other
Comparator / control treatment
Active control: control treatment will involve IPSRT and Medication Management without Group CR.
Control group
Active

Outcomes
Primary outcome [1] 320658 0
Change in Global Cognitive Composite score.
A single composite score (Global Cognitive Composite) representing overall cognitive performance on a cognitive testing battery.

Cognitive function will be measured at four time points (T0 = baseline, T1 = 6 months - pre-CR, T2 = 12-months - treatment-end, T3 = 18-months) with a battery of cognitive tasks designed to assess attention, working memory, memory, executive functioning and emotion processing. The battery will be as follows:
- Rey Auditory-Verbal Learning Task (Rey, 1964)
- Brief Visuospatial Memory Test (from MATRICS)
- Digit Span Forwards and Backwards (Wechsler, 1997)
- Trail Making Test – Part A and B (from MATRICS)
- Symbol Coding (BACS)
- Delis-Kaplan Executive Function System - Fluency Battery (Delis et al., 2001)
- Digit Symbol Coding (Wechsler, 1997)
- Continuous Performance Test (from MATRICS)
- Stroop Task (D-KEFS)
- Negative Affective Priming Task (Joormann, 2004)
- Reading the Mind in the Eyes Test (Baron-Cohen et al., 2001)
- Facial Expression Recognition Test (Harmer et al., 2003)
Timepoint [1] 320658 0
T1: 6 months (pre CR intervention) to T2: 12 months (end of treatment)
Secondary outcome [1] 372550 0
Change in global cognitive composite
As with the primary outcome, a single composite score (Global Cognitive Composite) representing overall cognitive performance at each cognitive assessment will be calculated.

The cognitive battery includes the following measures:
- Rey Auditory-Verbal Learning Task (Rey, 1964)
- Brief Visuospatial Memory Test (from MATRICS)
- Digit Span Forwards and Backwards (Wechsler, 1997)
- Trail Making Test – Part A and B (from MATRICS)
- Symbol Coding (BACS)
- Delis-Kaplan Executive Function System - Fluency Battery (Delis et al., 2001)
- Digit Symbol Coding (Wechsler, 1997)
- Continuous Performance Test (from MATRICS)
- Stroop Task (D-KEFS)
- Negative Affective Priming Task (Joormann, 2004)
- Reading the Mind in the Eyes Test (Baron-Cohen et al., 2001)
- Facial Expression Recognition Test (Harmer et al., 2003)
Timepoint [1] 372550 0
T0 (baseline) to T1 (6 months), T0 (baseline) to T2 (12 months), T0 (baseline) to T3 (18 months), T1 (6 months) to T3 (18 months)
Secondary outcome [2] 372551 0
Change in the cognitive domain score of 'verbal learning and memory' which includes several variables from the Rey Auditory Verbal Learning Test.
Timepoint [2] 372551 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months)
Secondary outcome [3] 372552 0
Change in subjective cognitive functioning, as measured with the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA).
Timepoint [3] 372552 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months)
Secondary outcome [4] 372553 0
Change in objective ('real world') general functioning, as measured with the University of California San Diego Performance Based Skills Assessment, Brief Version (UPSA-B).
Timepoint [4] 372553 0
T0 (baseline) to T2 (12 months)
Secondary outcome [5] 372554 0
Change in subjective general functioning, as measured with the Functioning Assessment Short Test (FAST).
Timepoint [5] 372554 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months) to T4 (24 months)
Secondary outcome [6] 372555 0
Change in mood morbidity, as measured with the Longitudinal Interview Follow-up Evalulation (LIFE).
Timepoint [6] 372555 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months) to T4 (24 months).
Secondary outcome [7] 372556 0
Change in self-reported quality of life, as measured with the Quality of Life in Bipolar Disorder (QoL-BD).
Timepoint [7] 372556 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [8] 372557 0
Change in self-reported biological and social rhythms, as measured with the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN).
Timepoint [8] 372557 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [9] 372558 0
Change in rumination, as measured with the Ruminative Responses Scale.
Timepoint [9] 372558 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [10] 372559 0
Change in personality dimensions, as measured with the Eysenck Personality Questionnaire – Brief Version (EPQ-BV).
Timepoint [10] 372559 0
T0 (baseline) to T2 (12 months).
Secondary outcome [11] 372560 0
Changes in medication adherence, as measured with the Medication Adherence Report Scale (MARS).
Timepoint [11] 372560 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months) to T4 (24 months).
Secondary outcome [12] 372561 0
Change in androgen levels in females, using blood concentrations of Free Testosterone, Total Testosterone, Free Androgen Index, and Sex Hormone Binding Globulin.
Timepoint [12] 372561 0
T0 (baseline) to T2 (12 months).
Secondary outcome [13] 372562 0
Change in C-Reactive Protein levels via blood test.
Timepoint [13] 372562 0
T0 (baseline) to T2 (12 months)
Secondary outcome [14] 372563 0
Change in blood levels of Vitamin C.
Timepoint [14] 372563 0
T0 (baseline) to T2 (12 months).
Secondary outcome [15] 373261 0
Change in the cognitive domain score of 'visuospatial learning and memory' which includes several variables from the Brief Visuospatial Memory Test.
Timepoint [15] 373261 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months)
Secondary outcome [16] 373262 0
Change in the cognitive domain score of 'executive function' which includes several variables from Digit Span, Trail Making Test Part B, Category Fluency, Category Switching, and the Stroop Colour-Word Interference Test.
Timepoint [16] 373262 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months)
Secondary outcome [17] 373263 0
Change in the cognitive domain score of 'psychomotor speed' which includes several variables from Trail Making Test Part A, and Symbol Coding.
Timepoint [17] 373263 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [18] 373264 0
Change in the cognitive domain score of 'sustained attention' which includes variables from the Continuous Performance Test.
Timepoint [18] 373264 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [19] 373265 0
Change in the cognitive domain score of 'emotion processing' which includes several variables from the Facial Expression Recognition Test, the Negative Affective Priming Test and the Reading the Mind in the Eyes Test.
Timepoint [19] 373265 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [20] 373266 0
Change in subjective cognitive performance (relating to cognitive assessment), as measured with the Perceived Cognitive Evaluation Questionnaire (developed by study investigators).
Timepoint [20] 373266 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [21] 373267 0
Change in subjective social/interpersonal functioning, as measured with the Social Adjustment Scale (SAS).
Timepoint [21] 373267 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [22] 373268 0
Change in depression symptoms as measured with the Quick Inventory of Depressive Symptomatology (QIDS).
Timepoint [22] 373268 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [23] 373269 0
Change in mania symptoms as measured with the Young Mania Rating Scale (YMRS).
Timepoint [23] 373269 0
T0 (baseline) to T1 (6 months) to T2 (12 months) to T3 (18 months).
Secondary outcome [24] 373273 0
Change in tumor necrosis factor - alpha via blood sample.
Timepoint [24] 373273 0
T0 (baseline) to T2 (12 months)
Secondary outcome [25] 373274 0
Change in soluble Interleukin-2 receptor via blood sample.
Timepoint [25] 373274 0
T0 (baseline) to T2 (12 months)
Secondary outcome [26] 373275 0
Change in soluble interleukin-6 receptor via blood sample.
Timepoint [26] 373275 0
T0 (baseline) to T2 (12 months)
Secondary outcome [27] 373276 0
Change in soluble tumor necrosis factor receptor type 1, via blood sample.
Timepoint [27] 373276 0
T0 (baseline) to T2 (12 months)

Eligibility
Key inclusion criteria
Adults ( > 18 years) with diagnosed mood disorder (BD I, BD II, BD NOS or MDD), confirmed with SCID-I.
Recently (within 3 months) discharged from Specialist Mental Health Services in Canterbury, Self- or clinician-reported cognitive impairment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Schizophrenia or schizoaffective disorder; severe alcohol or drug dependence; history of severe brain injury (loss of consciousness greater than 1 hour); previous course of cognitive remediation or electroconvulsive therapy in past 12 months; serious neurological or medical condition affecting cognitive function, pregnancy.

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
sequential randomisation list, stratified for diagnosis (bipolar versus MDD)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


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
This study has been powered based on cognitive outcomes demonstrated in a previous, preliminary study of Metacognitive Therapy for outpatients with major depressive disorder. The intervention produced positive effect size differences compared with a psychological therapy involving no cognitive intervention (CBT), of 0.6 on attention and executive functioning (Groves et al., 2015). For a similar effect size for the Global Cognitive Composite in the current study, 44 patients per group would be necessary for 80% power. We aim to recruit 50 participants per group, allowing for 12% drop-out in each group (n=6 in each group). All statistical tests will utilise a 2-tailed p-value of < 0.05 to indicate statistical significance.

The Global Cognitive Composite score will be created by averaging Z-scores across each cognitive domain. A change score from 6 to 12-month follow-up will then be calculated using the Global Cognitive Composite score from these time-points. Change scores on the Global Cognitive Composite will be compared between therapies (IPSRT-CR versus IPSRT alone) using t-tests.

Recruitment
Recruitment status
Not yet 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 outside Australia
Country [1] 21680 0
New Zealand
State/province [1] 21680 0
Canterbury

Funding & Sponsors
Funding source category [1] 303033 0
Government body
Name [1] 303033 0
Health Research Council of New Zealand (Sir Charles Hercus Health Research Fellowship)
Address [1] 303033 0
Physical Address: Level 3 - ProCARE Building, Grafton Mews, at 110 Stanley Street, Grafton, Auckland 1010, New Zealand
Postal Address: PO Box 5541, Wellesley Street, Auckland 1141, New Zealand
Country [1] 303033 0
New Zealand
Primary sponsor type
University
Name
Dr Katie Douglas
Address
Department of Psychological Medicine
University of Otago - Christchurch
PO Box 4345
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 303014 0
None
Name [1] 303014 0
Address [1] 303014 0
Country [1] 303014 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303587 0
Health and Disability Ethics Committees (New Zealand) - Northern B branch
Ethics committee address [1] 303587 0
Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington, 6011
New Zealand
Ethics committee country [1] 303587 0
New Zealand
Date submitted for ethics approval [1] 303587 0
09/04/2019
Approval date [1] 303587 0
16/05/2019
Ethics approval number [1] 303587 0
19/NTB/54

Summary
Brief summary
Mood disorders (major depressive disorder and bipolar disorder) seen in secondary care in New Zealand are highly recurrent, long-term conditions. Following short-term stabilisation of acute mood episodes, most patients continue to experience ongoing symptoms, relapses, and functional impairment.

A significant factor contributing to functional impairment, and to burden of symptoms and relapse, is cognitive impairment. Persisting cognitive impairment after recovery from a mood episode occurs in a high percentage of patients.

Our research has focused on examining psychological treatments which may promote full functional and symptomatic recovery in recurrent mood disorders. We have examined the effects on mood disturbance and cognitive function of adding a specific psychological treatment, Interpersonal and Social Rhythms Therapy (IPSRT), to usual treatment of mood disorders. IPSRT resulted in a reduction in symptom burden in this study, however, improvement in cognitive function was relatively limited.

A subsequent study added cognitive remediation (CR; a treatment specifically targeted at reducing cognitive impairment) to IPSRT in patients who have been discharged from SMHS. Our experience in this study suggests that CR commenced at the start of the stabilisation period is likely to be sub-optimal because of the level of mood symptoms which patients are experiencing at this stage. Research suggests that a group format for CR may be more efficient and produce more engagement from patients.

Thus, the proposed clinical trial will examine the effectiveness of group-based CR as an adjunct to IPSRT, in improving cognitive function (primary outcome), mood disturbance and general functioning, in patients with mood disorders. Biological measures of inflammatory markers and hormone levels in females will also be assessed over time.

Patients with a DSM-5 diagnosed mood disorder will be recruited at discharge from SMHS and will receive IPSRT to stabilise mood. After 6 months of IPSRT, patients will be randomised to additional group-based CR (IPSRT-CR) or no additional treatment (IPSRT alone). Follow-up assessments will occur at 18 months and 24 months.
Trial website
None.
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94166 0
Dr Katie Douglas
Address 94166 0
Department of Psychological Medicine
University of Otago - Christchurch
PO Box 4345
Christchurch 8140
Country 94166 0
New Zealand
Phone 94166 0
+64 3 3726700
Fax 94166 0
Email 94166 0
katie.douglas@otago.ac.nz
Contact person for public queries
Name 94167 0
Dr Katie Douglas
Address 94167 0
Department of Psychological Medicine
University of Otago - Christchurch
PO Box 4345
Christchurch 8140
Country 94167 0
New Zealand
Phone 94167 0
+64 3 3726700
Fax 94167 0
Email 94167 0
katie.douglas@otago.ac.nz
Contact person for scientific queries
Name 94168 0
Dr Katie Douglas
Address 94168 0
Department of Psychological Medicine
University of Otago - Christchurch
PO Box 4345
Christchurch 8140
Country 94168 0
New Zealand
Phone 94168 0
+64 3 3726700
Fax 94168 0
Email 94168 0
katie.douglas@otago.ac.nz

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