Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001328460
Ethics application status
Approved
Date submitted
5/08/2016
Date registered
23/09/2016
Date last updated
6/05/2021
Date data sharing statement initially provided
6/05/2021
Date results information initially provided
6/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Targeting Functional Recovery in Mood Disorders
Scientific title
A randomised controlled trial evaluating the addition of Cognitive Remediation to Interpersonal and Social Rhythms Therapy on cognitive functioning, everyday functioning, and mood morbidity in patients with severe mood disorders
Secondary ID [1] 289590 0
Nil Known
Universal Trial Number (UTN)
UTN: U111111781526
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mood disorders 299355 0
Major depressive disorder 299356 0
Bipolar disorder 299357 0
Condition category
Condition code
Mental Health 299340 299340 0 0
Depression
Mental Health 299341 299341 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Interpersonal and Social Rhythm Therapy combined with Cognitive Remediation.
IPSRT (Frank, 2005) is an integrative psychotherapy combining interpersonal psychotherapy (Klerman and Weissman, 1982) which targets interpersonal stressors such as interpersonal conflicts, role transitions and losses; with social rhythms therapy (aimed at establishing regularity in life patters such as sleeping, eating and social contact to stabilise circadian patterns). Both elements aim to stabilise functioning to minimise recurrence of mood episodes. IPSRT will be delivered on an individual basis in the clinic according to a manualised protocol. IPSRT will involve weekly sessions for 10-12 weeks followed by fortnightly for approximately 8 sessions, and then approximately 4 monthly sessions for the rest of the 1 year duration of treatment (total approximately 24 sessions). If there is deterioration in the patient’s mood, they may be seen more regularly and will be coded “crisis”. Care will be taken to minimise variation around the total number of sessions between groups. All sessions will be audio-taped and randomly selected and rated to ensure adherence to therapy protocols. All therapists will participate in regular and ongoing supervision.
Patients in the CR arm will be introduced by their therapists to a computerised cognitive remediation package (provided free of charge by Scientific Brain Training Professional (SBT-pro) - www.scientificbraintrainingpro.com). This will begin between weeks 7-9 (after allowing time for engagement with the therapist) and will continue at the 8 fortnightly sessions (12 CR sessions in total). Cognitive Remediation will be integrated into the IPSRT sessions. Patients will be asked to undertake three CR practice sessions per week between therapy sessions (length depending on clinical state) for the three months of the CR intervention. Therapists will provide on-line feedback once between face-to-face sessions. After 12 sessions, the package will continue to be available to patients for the rest of the intervention (i.e. until 12 months post baseline) should they wish to continue to practice. Therapist tasks completed during the therapy session will include:
a) reviewing performance and progress
b) discussing strategy on individual tasks and formulating a range of problem solving strategies
c) relating strategy to real-life situations (according to the manual of Bowie, Gupta and Holshausen)
d) selecting new tasks from the battery available.
Detailed information on patient adherence to prescribed CR practice sessions is available from the CR website, which gives information on practice sessions (dates, duration, tasks practiced, accuracy and speed).
Intervention code [1] 295196 0
Treatment: Other
Comparator / control treatment
Interpersonal and Social Rhythm Therapy combined with Cognitive Remediation.
IPSRT (Frank, 2005) is an integrative psychotherapy combining interpersonal psychotherapy (Klerman and Weissman, 1982) which targets interpersonal stressors such as interpersonal conflicts, role transitions and losses; with social rhythms therapy (aimed at establishing regularity in life patters such as sleeping, eating and social contact to stabilise circadian patterns). Both elements aim to stabilise functioning to minimise recurrence of mood episodes. IPSRT will be delivered on an individual basis in the clinic according to a manualised protocol. IPSRT will involve weekly sessions for 10-12 weeks followed by fortnightly for approximately 8 sessions, and then approximately 4 monthly sessions for the rest of the 1 year duration of treatment (total approximately 24 sessions). If there is deterioration in the patient’s mood, they may be seen more regularly and will be coded “crisis”. Care will be taken to minimise variation around the total number of sessions between groups. All sessions will be audio-taped and randomly selected and rated to ensure adherence to therapy protocols. All therapists will participate in regular and ongoing supervision.
Control group
Active

Outcomes
Primary outcome [1] 298814 0
Change in a composite cognitive score between baseline and 12 months The composite score will be calculated by computing z scores for each variable (change Baseline-Follow-up/standard deviation of the change). Scores will be adjusted so that a positive score reflects better performance for each variable. The z score for each variable will be added and divided by the number of variables to create a composite z score for change. The composite score is comprised of the following variables Groton Maze Learning Task - total errors, Rey Auditory-Verbal Learning Task - total words recalled lists 1-5 Rey Auditory-Verbal Learning Task - words recalled delayed recall Letter Fluency - total words, Category Fluency - total words Category Fluency Switching - total words Digit Span - total forwards plus backwards Timed Chase Test - time.
Timepoint [1] 298814 0
12 months
Secondary outcome [1] 325282 0
Change from baseline in composite cognitive measure comprising Groton Maze Learning Task, Rey Auditory-Verbal Learning Task, Rey Auditory-Verbal Learning Task, Letter Fluency, Category Fluency, Category Fluency Switching, Digit Span, Timed Chase Test, Change from baseline to 18 months
Timepoint [1] 325282 0
18 months
Secondary outcome [2] 325284 0
Functional Assessment Short test (FAST)
Post-randomisation change across all time points
Timepoint [2] 325284 0
Baseline, 6 months, 12 months, 18 months, 24 months
Secondary outcome [3] 326965 0
Longitudinal Interval Follow-Up Evaluation (LIFE25), Composite mean depression scores.
This will be supplemented by clinical notes if necessary - administered at baseline, 6, 12, 18 and 24 months by a rater blind to therapy and carried out by telephone
Post-randomisation change across all time points
Timepoint [3] 326965 0
Baseline, 6 months, 12 months, 18 months, 24 months
Secondary outcome [4] 326969 0
Longitudinal Interval Follow-Up Evaluation (LIFE25): Relapse rate
Post-randomisation change across all time points
Timepoint [4] 326969 0
Baseline, 6 months, 12 months, 18 months, 24 months
Secondary outcome [5] 326974 0
Social Adjustment Scale
Post-randomisation change across all time points

Timepoint [5] 326974 0
Baseline, 6 months, 12 months, 18 months,
Secondary outcome [6] 327245 0
Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA)
Post-randomisation change across all time points
Timepoint [6] 327245 0
Baseline, 6 months, 12 months, 18 months,
Secondary outcome [7] 327251 0
Groton Maze Learning Test
Post-randomisation change across all time points
Timepoint [7] 327251 0
Baseline, 12 months, 18 months,
Secondary outcome [8] 327271 0
Digit Span
Post-randomisation change across all time points
Timepoint [8] 327271 0
Baseline, 12 months, 18 months,
Secondary outcome [9] 327275 0
Category Fluency
Post-randomisation change across all time points
Timepoint [9] 327275 0
Baseline, 12 months, 18 months,
Secondary outcome [10] 327277 0
Category Fluency Switching
Post-randomisation change across all time points
Timepoint [10] 327277 0
Baseline, 12 months, 18 months,

Eligibility
Key inclusion criteria
1. 18 years or over
2. At point of discharge from Community Outpatient teams of Specialist Mental Health Services
3. Bipolar I, II or NOS or Major Depressive Disorder (can be in a current episode)
4 Subjective cognitive difficulties reported by the patient or judged by his/her referring clinician
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
IPSRT in the last 18 months
CR in the last 6 months
Primary diagnosis of severe substance use disorder
Diagnosis of schizophrenia or schizoaffective disorder
ECT in the last 6 months
History of severe brain injury (loss of consciousness > hour)
Engaged in other therapy concurrently
Diagnosis of neurodegenerative disease

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)
The randomisation sequence is generated ahead of the trial and is held in a secure filing cabinet in sealed envelopes by the independent staff member.
After the participants signs the consent form and complete the baseline assessment, the research assistant contacts the holder of the allocation who issues the next sealed envelope with the randomisation inside..


Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated in permuted blocks, stratified by bipolar/unipolar and site (Christchurch, Nelson, Wellington).
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
General linear models will be used to compare efficacy outcome measures between randomised groups. These models will include treatment group and stratum as fixed factors and as appropriate will include baseline measures as co-variates.
We have powered the study based on the cognitive outcomes demonstrated in our preliminary study of metacognitive therapy. This involved a cognitive intervention which produced positive effect size differences compared with a therapy involving no cognitive intervention, of 0.5 to 0.7 on attention and executive functioning. For a similar effect size of 0.5 for neuropsychological outcomes, 64 patients per group would also be necessary for 80% power. We aim to recruit 160 participants to allow up to 20% attrition (treatment drop-out or those who do not agree to take part in the second neuropsychological testing) to ensure a final group size in each arm of 64. All statistical tests will utilise a 2-tailed p-value of <0.05 to indicate statistical significance.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
There were modifications which appeared appropriate so the trial was stopped early to make way for a further trial
Date of first participant enrolment
Anticipated
7/11/2016
Actual
17/10/2016
Date of last participant enrolment
Anticipated
31/08/2020
Actual
5/08/2019
Date of last data collection
Anticipated
5/02/2021
Actual
5/02/2021
Sample size
Target
160
Accrual to date
Final
69
Recruitment outside Australia
Country [1] 8029 0
New Zealand
State/province [1] 8029 0
Canterbury, Nelson

Funding & Sponsors
Funding source category [1] 294068 0
University
Name [1] 294068 0
University of Otago
Country [1] 294068 0
New Zealand
Funding source category [2] 300196 0
University
Name [2] 300196 0
Canterbury Medical Research Foundation
Country [2] 300196 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Department of Psychological Medicine,
4 Oxford Terrace
PO Box 4345
Christchurch
8140
Country
New Zealand
Secondary sponsor category [1] 292899 0
None
Name [1] 292899 0
Address [1] 292899 0
Country [1] 292899 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295483 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 295483 0
Health and Disability Ethics Committees
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 295483 0
New Zealand
Date submitted for ethics approval [1] 295483 0
Approval date [1] 295483 0
14/06/2016
Ethics approval number [1] 295483 0
16/NTA/64

Summary
Brief summary
Aim
To compare a 12-month intervention involving Interpersonal and Social Rhythms Therapy combined with Cognitive Remediation (IPSRT-CR), with IPSRT alone, on cognitive functioning, everyday functioning, and mood morbidity in patients with a recurrent mood disorder.

Primary Hypothesis
IPSRT-CR, compared with IPSRT alone, will result in significantly improved cognitive functioning over the 12-month treatment period.
Secondary Hypotheses
a) IPSRT-CR will be associated with improved cognitive functioning at 18-month follow-up compared with IPSRT alone
b) IPSRT-CR will be superior to IPSRT alone in improving general functioning over the course of treatment and during the 12-month follow-up period
c) Overall mood related morbidity will be less during the treatment and in the 12-month follow-up period in patients randomised to the IPSRT-CR intervention

Sample
One hundred and sixty adults with mood disorder (bipolar disorder I or II, or Bipolar NOS or major depressive disorder (MDD)) will be recruited on discharge from SMHS in Canterbury, Nelson/Marlborough and Wellington.
Interventions
The 12-month IPSRT-CR intervention will involve IPSRT and Cognitive Remediation, the latter delivered by computer and supervised by therapists. The control intervention will be IPSRT alone (i.e., without the Cognitive Remediation component). Time spent with the therapist will be the same for each group.

Interpersonal and Social Rhythm Therapy
IPSRT will be delivered according to a manualised protocol. IPSRT will involve weekly sessions for 10-12 weeks followed by 8 fortnightly, and then 4 monthly sessions (total 24 sessions). If there is deterioration in the patient’s mood, they may be seen more regularly. All sessions will be audio-taped and randomly selected and rated to ensure adherence to therapy protocols. All therapists will participate in regular and ongoing supervision.

Cognitive Remediation
Patients will be introduced by their therapists to a computerised cognitive remediation package (provided free of charge by Scientific Brain Training Professional (SBT-pro) - www.scientificbraintrainingpro.com). This will begin between weeks 7-9 and will continue at the 8 fortnightly sessions (12 CR sessions in total). Patients will be asked to undertake three practice sessions per week between therapy sessions. Therapists will provide on-line feedback once between face-to-face sessions. After 12 sessions, the package will continue to be available to patients should they wish to continue to practice. Tasks completed during the therapy session will include:
a) reviewing performance and progress
b) discussing strategy on individual tasks and formulating a range of problem solving strategies
c) relating strategy to real-life situations
d) selecting new tasks from the battery available
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67110 0
Prof Richard Porter
Address 67110 0
Department of Psychological Medicine
University of Otago, Christchurch
PO Box 4345
4 Oxford Terrace
Christchurch
8140
Country 67110 0
New Zealand
Phone 67110 0
+6433720400
Fax 67110 0
+6433720407
Email 67110 0
[email protected]
Contact person for public queries
Name 67111 0
Ms Lynere Wilson
Address 67111 0
Department of Psychological Medicine
University of Otago, Christchurch
PO Box 4345
4 Oxford Terrace
Christchurch
8140
Country 67111 0
New Zealand
Phone 67111 0
+6433720400
Fax 67111 0
Email 67111 0
[email protected]
Contact person for scientific queries
Name 67112 0
Prof Richard Porter
Address 67112 0
Department of Psychological Medicine
University of Otago, Christchurch
PO Box 4345
4 Oxford Terrace
Christchurch
8140
Country 67112 0
New Zealand
Phone 67112 0
+6433720400
Fax 67112 0
+6433720407
Email 67112 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
This was not part of the protocol


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
SourceTitleYear of PublicationDOI
EmbaseA randomised controlled trial of psychotherapy and cognitive remediation to target cognition in mood disorders.2022https://dx.doi.org/10.1111/acps.13387
N.B. These documents automatically identified may not have been verified by the study sponsor.