ANZCTR - Registration

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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 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]

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

Condition category

Condition code

Mental Health

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]

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]

Social and occupational functioning, as rated on the Social and Occupational Functioning Assessment Scale (SOFAS).

Timepoint [1]

6, 12, 24 months

Secondary outcome [1]

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]

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?

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

Accrual to date

Final

118

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3052

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC project grant

Address [1]

National Health and Medical Research Council
GPO Box 1421 (Level 1, 16 Marcus Clarke Street)
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other

Name

Orygen

Address

35 Poplar Road (Locked Bag 10)
Parkville
Victoria 3052

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health, Office for Research

Ethics committee address [1]

Royal Melbourne Hospital
Parkville
Victoria 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

17/07/2007

Ethics approval number [1]

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

Prof Patrick McGorry

Address

Orygen, The National Centre of Excellence in Youth Mental Health
Locked Bag 10 (35 Poplar Road)
Parkville Victoria 3052

Country

Australia

Phone

+61 3 9966 9100

Fax

pat.mcgorry@orygen.org.au

Contact person for public queries

Name

Shona Francey

Address

Orygen, Parkville, Victoria, 3052

Country

Australia

Phone

+61 3 9966 9226

Fax

shona.francey@orygen.org.au

Contact person for scientific queries

Name

Shona Francey

Address

35 Poplar Road
Parkville
Victoria 3052

Country

Australia

Phone

+61 3 9966 9226

Fax

shona.francey@orygen.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Citation	Link	Email	Other Details	Attachment
14318	Informed consent form			shona.francey@orygen.org.au
14319	Ethical approval			shona.francey@orygen.org.au

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Should people with psychosis be supported in choosing cognitive therapy as an alternative to antipsychotic medication: A commentary on current evidence.	2019	https://dx.doi.org/10.1016/j.schres.2018.03.010
Embase	Staged 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.	2019	https://dx.doi.org/10.1111/eip.12716
Embase	Psychological interventions for psychosis in adolescents.	2020	https://dx.doi.org/10.1002/14651858.CD009533.pub2
Embase	Functional 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.	2021	https://dx.doi.org/10.1001/jamapsychiatry.2021.1422
Embase	Gradients of striatal function in antipsychotic-free first-episode psychosis and schizotypy.	2023	https://dx.doi.org/10.1038/s41398-023-02417-2
Embase	Isolating 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).	2023	https://dx.doi.org/10.1111/eip.13353

N.B. These documents automatically identified may not have been verified by the study sponsor.

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