Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000870358
Ethics application status
Approved
Date submitted
5/05/2017
Date registered
15/06/2017
Date last updated
17/04/2024
Date data sharing statement initially provided
10/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does Antipsychotic Dose Reduction in combination with Evidence-Based Intensive Recovery Treatment (EBIRT) Lead to Better Functional Recovery in First Episode Psychosis: A Randomised Controlled Trial
Scientific title
Does Antipsychotic Dose Reduction in combination with Evidence-Based Intensive Recovery Treatment (EBIRT) Lead to Better Functional Recovery in First Episode Psychosis: A Randomised Controlled Trial
Secondary ID [1] 291524 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Reduce
Linked study record

Health condition
Health condition(s) or problem(s) studied:
First Episode Psychosis 302611 0
Condition category
Condition code
Mental Health 302133 302133 0 0
Psychosis and personality disorders
Mental Health 302134 302134 0 0
Schizophrenia
Public Health 302135 302135 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Evidence-Based Intensive Recovery Treatment (EBIRT) combines two well-validated and manualised psychosocial interventions; Individual Placement and Support (IPS) for vocational recovery and Cognitive Behaviour Therapy (CBT) for Relapse Prevention. IPS is (a) focussed upon competitive employment, education or training as an outcome; and (b) focussed upon immediate job/education searching. EBIRT will be delivered in two phases; a 9-month intensive phase which entails two sessions of individual therapy per week for 9-months, followed by a 6-9 month (dependent on tenure remaining in service)- maintenance/monitoring phase in which individual therapy sessions will be delivered every 4-6 weeks. EBIRT will be provided by a therapist trained in CBT and is comprised of six or more modules of therapy delivered over the 9 month intensive period. Each CBT session will be for approximately 1 hour in length and will aimed to be delivered twice a week, but will be dependent on the participants availability. There is no minimum required session per week.. IPS will be delivered separately by a trained vocational support worker. The aim will be for IPS to be delivered weekly but this is flexible and will be dependent on the individuals vocational support requirements. The six phases of EBIRT intervention include: (1) initiation of vocational intervention (2) formulation and agenda setting; including vocational goal setting; (3) engagement and assessment for recovery and risk for relapse; (4) psychoeducation with a focus on relapse; (5) early warning signs and relapse planning – will also involve family members with participant’s consent; and, treatment and progress review (6). Additional optional modules may be drawn upon depending on case formulation and clinical determination in collaboration with the participant include: substance abuse, stress management, and co-morbid anxiety and depression at the investigator’s discretion. In tandem with EBIRT, participants will be randomly assigned following baseline assessment to either the DRS or AMTx treatment conditions.

Dose Reduction Strategy (DRS+) group: Participants who are randomised to this arm of the trial will be offered a gradual dose reduction of their antipsychotic medication. Medication will be tapered under close medical supervision over 3-months after allocation to the DRS group to avoid relapse due to abrupt discontinuation. The rate of tapering will be a 25% dose reduction (or as near to 25% as the medication allows) of the pre-reduction dose every month for 3 months, If clinically safe as determined by the Early Psychosis Prevention and Intervention Centre (EPPIC) treating team. If discontinuation criteria (psychotic relapse or exacerbation) is met at any time throughout the study, the minimum therapeutic dose will be continued or reinstated. As per routine guidelines, the young person’s treating doctor will review their treatment options with them at discharge from EPPIC, this will coincide with their end of treatment. The participant will then remain on the last dose for the remainder of EBIRT after the 3 months of DRS unless clinically indicated, in which case anti-psychotic medication can be reinstated. This will be done in consultation with the Principal Investigator, the Consultant Psychiatrist and the participants treating team.

Treatment fidelity will be ensured via the following procedures: (a) treatment manuals detailing treatment procedures; (b) ongoing weekly group supervision providing feedback with clinical supervisors; and (c) audio-taping of EBIRT therapy sessions for all participants, unless they have explicitly stated they do not wish to be record. These recordings will be independently rated using previously developed fidelity measures.
Intervention code [1] 297594 0
Treatment: Other
Intervention code [2] 298067 0
Behaviour
Comparator / control treatment
Antipsychotic Maintenance Treatment (AMTx) group: Participants will continue to receive medication as indicated, concordant with the Australian Clinical Practice Guidelines for FEP for the 15-18 month treatment phase of the study]. These guidelines recommend the use of the lowest effective dose of atypical antipsychotics. . As per routine guidelines, the young person’s treating doctor will review their treatment options with them at discharge from EPPIC, this will coincide with their end of treatment. The AMT group will also receive the same level/duration of EBIRT as the DRS Group
All trial participants will have access to all components of treatment at EPPIC, such as psychiatric care, case management, psychosocial program, acute inpatient care and outreach as clinically indicated.

40 healthy controls aged 15-25 years (inclusive), living in the EPPIC catchment, and have no history of mental illness, neurological condition or antipsychotic medication treatment will also be recruited. They will be scanned, cognitively assessed and have physical health indicators measured (except bloods) at the same four time points as the DRS+ and AMTx+ groups (baseline, 9-months, 15-months and 24 months). This will provide objective control data to determine whether there are physical health, brain volume and neural activation or cognition changes and if they are related to illness, medication or normal development.
Control group
Dose comparison

Outcomes
Primary outcome [1] 301566 0
Social and Occupational functioning assessed using the Social and Occupational Functioning Scale (SOFAS).
Timepoint [1] 301566 0
24 months
Secondary outcome [1] 333044 0
Physical health is a composite secondary outcome and will be measured by clinical blood analysis evaluating glucose, haemoglobin A1C, and lipid levels in the treatment groups only. Blood pressure, weight, height and waist circumference will also be recorded.
Timepoint [1] 333044 0
24-months.
Secondary outcome [2] 334818 0
Brain volumes/activity is a composite secondary outcome- Brain volume will be quantified in both treatment groups and healthy controls by high-resolution magnetic resonance imaging (MRI). In addition to structural MRI imaging, functional resting state will also be performed.
Timepoint [2] 334818 0
24 Months
Secondary outcome [3] 334823 0
Remission and relapse rates of positive symptoms is a composite secondary outcome and will be assessed using the Brief Psychiatric Rating Scale (exBPRS) in treatment groups only. Remission of negative symptoms will be assessed using the Scale for Assessment of Negative Symptoms (SANS).
Timepoint [3] 334823 0
24 Months
Secondary outcome [4] 334827 0
Cognitive functioning will assessed with neurocognitive tests (including the Brief Assessment of Cognition in Schizophrenia (BACS) will be used to assess neuropsychological functioning in all groups.
Timepoint [4] 334827 0
24 months

Eligibility
Key inclusion criteria
A participant will be considered eligible for inclusion in this study if all of the following criteria apply:

1. Current client of EPPIC
2. A confirmed diagnosis of first episode of a DSM-5 psychotic disorder or mood disorder with psychotic features as determined by the Structured Clinical Interview for DSM-5 Axis I Disorders, patient version (SCID-RV);
3. Aged 15-25 years (inclusive).
4. greater than or equal to 3 months of remission on positive symptoms of psychosis in the first year of antipsychotic treatment at EPPIC (a score of greater than or equal to 3 (mild) on the hallucinations, unusual thought disorder, conceptual disorganisation, and suspiciousness subscale items of the Brief Psychiatric Rating Scale (BPRS) for the past two weeks and a score greater than or equal to 3 on the hallucinations, unusual thought content, conceptual disorganisation, and suspiciousness subscales of the BRPS for the past 3 months based on a systematic clinical file review and collateral information collected from the participant’s treating team in EPPIC as needed).
5. Low suicidality defined as a score of 4 or below on the BPRS sustained for the past 1-month period from baseline.
6. The young person is willing for their carer to be informed about the study and will have at least weekly contact with their carer.
7. Ability to provide written informed consent.
• Where participants are under 18 years of age, consent will also be obtained from the participant’s parent or legal guardian. The parent or legal guardian and participant will both be required to sign a consent form.

Healthy controls will be aged 15-25 years (inclusive), who are able to attend appointments in Parkville, and have no self-reported history of mental illness, antipsychotic medication treatment, or neurological disorder.
Minimum age
15 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
FEP Exclusion Criteria
Participants who meet any of the following criteria will not be eligible for participation in this study:
1. A documented history of an intellectual disability or IQ <70
2. Inability to converse in or read English
3. Women who are currently pregnant or breastfeeding
4. Neurological disorder


Health Controls Exclusion Criteria:
Healthy controls will have no self-reported history of mental illness (including no history of a psychotic disorder), anti psychotic medication treatment or neurological disorder.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/07/2017
Actual
20/06/2017
Date of last participant enrolment
Anticipated
Actual
4/03/2020
Date of last data collection
Anticipated
4/03/2022
Actual
30/06/2022
Sample size
Target
180
Accrual to date
Final
44
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 296012 0
Government body
Name [1] 296012 0
National Health and Medical Research Council (NHMRC)
Country [1] 296012 0
Australia
Primary sponsor type
Other
Name
Orygen, the National Centre of Excellence in Youth Mental Health
Address
35 Poplar Road, Parkville, VIC 3052
Country
Australia
Secondary sponsor category [1] 294900 0
None
Name [1] 294900 0
Address [1] 294900 0
Country [1] 294900 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297273 0
Melbourne Health Ethics Committee
Ethics committee address [1] 297273 0
Ethics committee country [1] 297273 0
Australia
Date submitted for ethics approval [1] 297273 0
Approval date [1] 297273 0
02/02/2017
Ethics approval number [1] 297273 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73542 0
Prof Eoin Killackey
Address 73542 0
Orygen, 35 Poplar Road, Parkville, VIC 3052
Country 73542 0
Australia
Phone 73542 0
+61 3 93422800
Fax 73542 0
Email 73542 0
[email protected]
Contact person for public queries
Name 73543 0
Alexandra Stainton
Address 73543 0
Orygen, 35 Poplar Road, Parkville, VIC 3052
Country 73543 0
Australia
Phone 73543 0
+61448121435
Fax 73543 0
Email 73543 0
alexandra,[email protected]
Contact person for scientific queries
Name 73544 0
Eoin Killackey
Address 73544 0
Orygen, 35 Poplar Road, Parkville, VIC 3052
Country 73544 0
Australia
Phone 73544 0
+61 3 93422800
Fax 73544 0
Email 73544 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All available data, de-identified.
When will data be available (start and end dates)?
Data are available immediately and for an indefinite time
Available to whom?
Data will potentially be available to researchers from not-for profit organisations, commercial organisations or other based in any location. All data requests will be considered by the data custodian and the primary sponsor on a case-by-case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted. For further information, see Orygen data management policy.
Available for what types of analyses?
To any type of analyses. Assessed on a case-by-case basis.
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health). Search for the ANZCTR number in the catalogue to find datasets associated with this trial.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1834Study protocol    372621-(Uploaded-10-04-2019-09-14-40)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseDiscontinuation of antipsychotic medication-time to rethink trial design.2020https://dx.doi.org/10.1016/S2215-0366%2820%2930340-0
Dimensions AIPanel sampling in health research2020https://doi.org/10.1016/s2215-0366(20)30358-8
N.B. These documents automatically identified may not have been verified by the study sponsor.