Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000608460
Ethics application status
Approved
Date submitted
26/11/2007
Date registered
28/11/2007
Date last updated
2/12/2021
Date data sharing statement initially provided
2/12/2021
Date results information initially provided
2/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised placebo controlled trial of intensive psychosocial treatment plus or minus anti-psychotic medication for first episode psychosis with low-risk of self-harm or aggression. The STAGES Study: Staged Treatment and Acceptability Guidelines in Early Psychosis
Scientific title
A randomised placebo controlled trial of intensive psychosocial treatment plus or minus anti-psychotic medication for first episode psychosis with low-risk of self-harm or aggression to evaluate the impact on functioning and symptomatology. The STAGES Study: Staged Treatment and Acceptability Guidelines in Early Psychosis
Secondary ID [1] 280394 0
Nil
Universal Trial Number (UTN)
Trial acronym
STAGES study of first episode psychosis
Linked study record

Health condition
Health condition(s) or problem(s) studied:
First episode psychosis 2576 0
Condition category
Condition code
Mental Health 2686 2686 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intensive psychosocial intervention minus antipsychotic medication. Participants randomised to this intervention will be administered placebo tablets. The psychosocial intervention consists of four modules: intensive case management (engagement, problem solving, advocacy and support); close monitoring and crisis response; cognitive-behaviour therapy for symptoms; family support and education. The intensive psychosocial intervention will consist of twice-weekly contact with the treating team during the first 2 months of the study, and weekly contact after the first 2 months. In total, the treatment will be provided for 6 months. Placebo medication will be titrated in 1mg increments at the discretion of the treating clinician over a four-week period, until a maximum maintenance dose of 6mg/day is reached, if required. Dose will be held at 2mg/day if adequate response is observed within 4 weeks. The medication will be packaged to allow flexible dosing.
Intervention code [1] 2312 0
Treatment: Other
Comparator / control treatment
Intensive psychosocial intervention plus antipsychotic medication. This consists of four modules: intensive case management (engagement, problem solving, advocacy and support); close monitoring and crisis response; cognitive-behaviour therapy for symptoms; family support and education. The intensive psychosocial intervention will consist of twice-weekly contact with the treating team during the first 2 months of the study and weekly contact after the first 2 months. In total, the treatment will be provided for 6 months. The antipsychotic medication will be risperidone. Trial medication will be titrated in 1mg increments at the discretion of the treating clinician over a four-week period, until a maximum maintenance dose of 6mg/day is reached, if required. Dose will be held at 2mg/day if adequate response is observed within 4 weeks. The medication will be packaged to allow flexible dosing.
Control group
Active

Outcomes
Primary outcome [1] 3589 0
Social and occupational functioning, as rated on the Social and Occupational Functioning Assessment Scale (SOFAS).
Timepoint [1] 3589 0
6, 12, 24 months
Secondary outcome [1] 6012 0
Psychiatric symptomatology, including positive psychotic symptoms, negative psychotic symptoms, and mood and anxiety symptoms, as measured by the Brief Psychiatric Rating Scale (BPRS).
Timepoint [1] 6012 0
6, 12, 24 months

Eligibility
Key inclusion criteria
• Ability to give informed consent (Capacity to give informed consent will be assessed by an Orygen Youth Health doctor in cases where an intellectual disability is suspected)
• Adequate comprehension of English to enable study assessments to be conducted
• Low suicidality (as defined by a score of < 5 on the exBPRS Suicidality subscale, i.e., no more than occasional suicidal thoughts with no plan or intent)
• Low aggressiveness (as defined by a score of < 5 on the exBPRS Hostility scale, i.e., may have been angry or yelled on several occasions but has not threatened people or thrown objects)
• Currently living in stable accommodation, in regular contact with people who support the young person's participation in the study.
Minimum age
15 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- more than 7 days treatment with neuroleptic medication for the current psychotic episode
- A lifetime maximum dose of antipsychotic medication greater than an equivalent to 1750mg of chlorpromazine
- duration of untreated psychosis for longer than 6 months
- current pregnancy
- previous treatment with lithium or anticonvulsant medication for manic episode

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)
A psychiatrist, case manager and research assistant will determine if the subject is eligible for inclusion in the trial. Allocation will be concealed by contacting the holder of the allocation schedule who is "off-site".
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A stratified randomisation design will be used to allocate subjects to either one of the treatment groups. It has been established that duration of untreated psychosis and gender are associated with functional outcome, the key outcome measure in this study. Hence, we will be using characteristics as stratifying factors in the randomisation, since any chance imbalances on these prognostic variables may bias the analysis. Duration of untreated psychosis will be included as a three-level factor; < 1 month; 1 month to < 3 months, 3 months to 6 months. Along with gender, this will result in six separate randomisation lists from which subjects will be drawn. Subjects will be allocated to either one of the treatment groups using randomly permuted blocks within each stratum, to ensure that subject allocation to the treatment groups is approximately equal.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/11/2007
Actual
7/04/2008
Date of last participant enrolment
Anticipated
Actual
31/12/2018
Date of last data collection
Anticipated
4/11/2018
Actual
31/07/2019
Sample size
Target
95
Accrual to date
Final
118
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 498 0
3052

Funding & Sponsors
Funding source category [1] 2822 0
Government body
Name [1] 2822 0
NHMRC project grant
Country [1] 2822 0
Australia
Primary sponsor type
Other
Name
Orygen
Address
35 Poplar Road (Locked Bag 10)
Parkville
Victoria 3052
Country
Australia
Secondary sponsor category [1] 2549 0
None
Name [1] 2549 0
Address [1] 2549 0
Country [1] 2549 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4758 0
Melbourne Health, Office for Research
Ethics committee address [1] 4758 0
Royal Melbourne Hospital
Parkville
Victoria 3052
Ethics committee country [1] 4758 0
Australia
Date submitted for ethics approval [1] 4758 0
Approval date [1] 4758 0
17/07/2007
Ethics approval number [1] 4758 0
2007.016

Summary
Brief summary
Background Over the last decade, there has been a significant shift in psychiatric services towards a greater focus on early intervention for psychotic illnesses. This has raised the question of what the most appropriate form of treatment is for people (very) early in the course of a first psychotic episode. It is also possible that due to the efforts of early detection programs, the composition of first episode psychosis (FEP) cohorts may have changed towards including those who may have a more benign course of psychotic symptoms and thus may respond to more benign treatments. Aims The purpose of this project is to investigate whether a sub-group of young people can recover from FEP with intensive psychosocial intervention but without taking antipsychotic medication. Although we know that antipsychotic medication is usually helpful in assisting recovery from psychosis, medication may not be essential for effective treatment in all cases. Furthermore, there is also evidence that psychological treatment is helpful and may be sufficient and more acceptable to young people who are experiencing FEP. Design Participants will be young people, aged 15 - 25 receiving treatment from the Early Psychosis Prevention and Intervention Centre (EPPIC) of ORYGEN Youth Health. Approximately 95 young people will be randomised to two treatment groups: 1. Medication (risperidone) plus intensive psychosocial treatment (MIPT) 2. Placebo plus intensive psychosocial treatment (PIPT) The trial will be of 6 months duration. Intensive contact with participants will be maintained by case managers and psychiatrists throughout this time. Clinical, neuropsychological and neuroimaging measures will be taken at baseline and at various follow-up points (3, 6, 12, 24 months). Outcomes The primary outcome of interest is functional and symptomatic outcome (at 6, 12 and 24 months) in each treatment group. Specifically, it is of interest whether participants in the PIPT group achieve similar levels of functional and symptomatic improvement compared to the MIPT group at short- and long-term follow-up. Another outcome of interest is the proportion of the PIPT group who are not placed on antipsychotic medication during the 6-month period. These participants will have achieved satisfactory remission without antipsychotic medication. This sub-group will be compared on functioning and symptom scales to those randomised to the medication group and to those for whom antipsychotic medication was commenced due to worsening mental state and/or risk. Characteristics of this group will be analysed to determine the sub-group of FEP patients who may achieve remission from symptoms without antipsychotic medication. A PhD project has been added that will recruit a healthy comparison group to examine changes in physical health and neuropsychological functioning over time in the study age group.
Trial website
Trial related presentations / publications
Francey, S.M., O’Donoghue, B., Nelson, B., Graham, J., Baldwin, L., Fornito, A., Allott, K., Alvarez-Jimenez, M., Harrigan, S., Yuen, H.K. & McGorry, P.D. (2018, February). Antipsychotic medication in first-episode psychosis: An RCT to assess the risk-benefit ratio. Paper presented at the World Psychiatric Association Thematic Congress, Melbourne, Australia.
Public notes

Contacts
Principal investigator
Name 28208 0
Prof Patrick McGorry
Address 28208 0
Orygen, The National Centre of Excellence in Youth Mental Health
Locked Bag 10 (35 Poplar Road)
Parkville Victoria 3052
Country 28208 0
Australia
Phone 28208 0
+61 3 9966 9100
Fax 28208 0
Email 28208 0
[email protected]
Contact person for public queries
Name 11365 0
Shona Francey
Address 11365 0
Orygen, Parkville, Victoria, 3052
Country 11365 0
Australia
Phone 11365 0
+61 3 9966 9226
Fax 11365 0
Email 11365 0
[email protected]
Contact person for scientific queries
Name 2293 0
Shona Francey
Address 2293 0
35 Poplar Road
Parkville
Victoria 3052
Country 2293 0
Australia
Phone 2293 0
+61 3 9966 9226
Fax 2293 0
Email 2293 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 study commenced in 2007, when data sharing was less common, and participants were not asked to give consent to data sharing. Thus it is not considered ethical to share individual participant data when informed consent has not been obtained.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14318Informed consent form  [email protected]
14319Ethical approval  [email protected]



Results publications and other study-related documents

Documents added manually

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseShould people with psychosis be supported in choosing cognitive therapy as an alternative to antipsychotic medication: A commentary on current evidence.2019https://dx.doi.org/10.1016/j.schres.2018.03.010
EmbaseStaged treatment and acceptability guidelines in early psychosis study (STAGES): A randomized placebo controlled trial of intensive psychosocial treatment plus or minus antipsychotic medication for first-episode psychosis with low-risk of self-harm or aggression. Study protocol and baseline characteristics of participants.2019https://dx.doi.org/10.1111/eip.12716
EmbasePsychological interventions for psychosis in adolescents.2020https://dx.doi.org/10.1002/14651858.CD009533.pub2
EmbaseFunctional Connectivity in Antipsychotic-Treated and Antipsychotic-Naive Patients with First-Episode Psychosis and Low Risk of Self-harm or Aggression: A Secondary Analysis of a Randomized Clinical Trial.2021https://dx.doi.org/10.1001/jamapsychiatry.2021.1422
EmbaseGradients of striatal function in antipsychotic-free first-episode psychosis and schizotypy.2023https://dx.doi.org/10.1038/s41398-023-02417-2
EmbaseIsolating the impact of antipsychotic medication on metabolic health: Secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naive first-episode psychosis (the STAGES study).2023https://dx.doi.org/10.1111/eip.13353
N.B. These documents automatically identified may not have been verified by the study sponsor.