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Trial registered on ANZCTR


Registration number
ACTRN12615000635561
Ethics application status
Approved
Date submitted
27/01/2015
Date registered
18/06/2015
Date last updated
16/11/2023
Date data sharing statement initially provided
16/11/2023
Date results provided
16/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Canakinumab Add-on Treatment in Schizophrenia (CATS)
Scientific title
The effect of canakinumab adjunctive treatment on symptoms and cognition in people with schizophrenia displaying elevated peripheral inflammatory markers
Secondary ID [1] 286056 0
Nil known
Universal Trial Number (UTN)
U1111-1166-6037
Trial acronym
CATS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
schizophrenia 294036 0
schizoaffective disorder 295318 0
Condition category
Condition code
Mental Health 294338 294338 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Canakinumab 180 mg subcutaneous injection will be administered once and lasts for up to 8 weeks as an adjunctive treatment to each participant's usual antipsychotic treatment by one of our study physicians who will be blind to treatment condition.
Intervention code [1] 291044 0
Treatment: Drugs
Comparator / control treatment
placebo, sodium chloride for injection 0.9% subcutaneous injection administered once
Control group
Placebo

Outcomes
Primary outcome [1] 294140 0
Positive and Negative Syndrome Scale Score Total Score
Timepoint [1] 294140 0
1 week, 4 weeks and 8 weeks and 4 months.
Primary outcome [2] 295349 0
Positive and Negative Syndrome Scale Score Positive Symptoms Score
Timepoint [2] 295349 0
1 week, 4 weeks and 8 weeks and 4 months.
Primary outcome [3] 295350 0
Positive and Negative Syndrome Scale Score Negative Symptoms Score
Timepoint [3] 295350 0
4 weeks and 8 weeks
Secondary outcome [1] 312599 0
Controlled Oral Word Association Test verbal (letter) fluency test
Timepoint [1] 312599 0
1 week, 4 weeks and 8 weeks and 4 months.
Secondary outcome [2] 315398 0
Controlled Oral Word Association Test verbal (category) fluency test
Timepoint [2] 315398 0
1 week, 4 weeks and 8 weeks and 4 months.

Eligibility
Key inclusion criteria
diagnosis of schizophrenia or schizoaffective disorder
between 18 and 55 years of age
have been receiving antipsychotic medication for at least 1 year
display elevated neutrophil to lymphocyte ratio greater than 2 or
an elevated IL-1beta ELISA assay
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
concurrent DSM-V axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder
display a neutrophil to lymphocyte ratio less than 2 or
display normal IL-1beta ELISA levels
history of current substance abuse or dependence (within the past 3 years)
head injuries with loss of consciousness
seizures
central nervous system infection
untreated diabetes or hypertension
mental retardation
learning disorder
history of pervasive developmental disorder
present systemic infections
history of recurrent infections
have been recently administered live vaccines
neutropenia (defined by neutrophil count)
positive pregnancy blood test
lactating
intends to become pregnant
refuses to use contraception or remain abstinent till 1 month after the study
history of causing harm to self or others
receiving tumor necrosis factor inhibitors
receiving clozapine
hypersensitivity or contraindications to canakinumab

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 randomization table was constructed by an independent statistician who supplied the randomization table to the Prince of Wales Hospital (POWH) Pharmacy Clinical trials Unit which is offsite to Neuroscience Research Australia. The POWH Pharmacy Clinical Trials Unit will maintain the double blind nature of the trial and assign a patient number and distribute the injection in a blinded manner to the nurse physician administering the injection. Upon disbursement of the (active or placebo) treatment, the Pharmacy will reconstitute the injection or placebo and provide the tape concealed and numbered vial to the investigators for injection.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomization has been performed using STATA 13.1
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
At present, there have been no studies of canakinumab in people with schizophrenia, thus a direct power analysis in relation to the effects of canakinumab on symptoms reduction and cognitive enhancement in schizophrenia is not available. However, we can use the effect sizes from studies of anti-inflammatory drugs (e.g., cyclooxygenase-2, COX-2, inhibitors) as an estimate of the effect size of canakinumab treatment on symptoms of schizophrenia. There are two published studies (Akhondzadeh S., et al. 2007, Schizophr Res 90:179-185; Muller N., et al. 2010, Schizophr Res 121:118-124) using COX-2 inhibitors to treat symptoms of schizophrenia that have reported effects on the total PANSS score and provide the relevant information (means and standard deviations) from which effect sizes can be calculated. The mean effect size on PANSS total scores from these two COX-2 inhibitor studies in schizophrenia was 1.07. Thus, we have determined that 30 individuals (15 per group) are necessary and sufficient to detect significant effects of canakinumab treatment on PANSS total scores based on our sample size analysis that shows 13.7 participants per group (27.4 total sample size) for a two-tailed significance test with an a level set at .05, d of 2.80, and an effect size of 1.07 for PANSS total score (Akhondzadeh S., et al. 2007; Muller N., et al. 2010) will be required to attain a power value of .80.

In determining the extent to which canakinumab improves psychotic symptoms and cognition, separate ANOVAs or ANCOVAs will be used for PANSS positive symptom score, PANSS negative symptom score, PANSS total score, and COWAT verbal (letter) fluency score to compare conditions (canakinumab versus placebo and/or baseline) with respect to treatment effects. The level of significance for this study will be set at p < .05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
29/06/2015
Actual
25/06/2015
Date of last participant enrolment
Anticipated
31/05/2017
Actual
27/06/2017
Date of last data collection
Anticipated
29/09/2017
Actual
27/09/2017
Sample size
Target
30
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7845 0
Lyell McEwin Hospital - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 290643 0
Charities/Societies/Foundations
Name [1] 290643 0
Stanley Medical Research Institute
Country [1] 290643 0
United States of America
Funding source category [2] 296198 0
Charities/Societies/Foundations
Name [2] 296198 0
Brain and Behavior Research Foundation
Country [2] 296198 0
United States of America
Funding source category [3] 296199 0
University
Name [3] 296199 0
Brain Sciences UNSW
Country [3] 296199 0
Australia
Primary sponsor type
Other
Name
Neuroscience Research Australia
Address
Barker Street
Randwick, New South Wales 2031 Australia
Country
Australia
Secondary sponsor category [1] 289336 0
University
Name [1] 289336 0
University of New South Wales
Address [1] 289336 0
Kensington, New South Wales 2052
Country [1] 289336 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292275 0
New South Wales Health South Eastern Sydney Local Health District HREC
Ethics committee address [1] 292275 0
Ethics committee country [1] 292275 0
Australia
Date submitted for ethics approval [1] 292275 0
Approval date [1] 292275 0
08/01/2015
Ethics approval number [1] 292275 0
14/072 (HREC/14/POWH/386
Ethics committee name [2] 297440 0
Northern Adelaide Local Health Network
Ethics committee address [2] 297440 0
Ethics committee country [2] 297440 0
Australia
Date submitted for ethics approval [2] 297440 0
Approval date [2] 297440 0
25/11/2016
Ethics approval number [2] 297440 0
14/POWH/386 and SSA/16/NALHN/71

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

Contacts
Principal investigator
Name 54418 0
Dr Thomas Weickert
Address 54418 0
Neuroscience Research Australia
Barker Street
Randwick, NSW 2031 Australia
Country 54418 0
Australia
Phone 54418 0
+61 2 9399 1730
Fax 54418 0
+61 2 9399 1034
Email 54418 0
t.weickert@neura.edu.au
Contact person for public queries
Name 54419 0
Thomas Weickert
Address 54419 0
Neuroscience Research Australia
barker Street
Randwick, NSW 2031 Australia
Country 54419 0
Australia
Phone 54419 0
+61 2 9399 1730
Fax 54419 0
+61 2 9399 1034
Email 54419 0
t.weickert@neura.edu.au
Contact person for scientific queries
Name 54420 0
Thomas Weickert
Address 54420 0
Neuroscience Research Australia
Barker Street
Randwick, NSW 2031 Australia
Country 54420 0
Australia
Phone 54420 0
+61 2 9399 1730
Fax 54420 0
+61 2 9399 1034
Email 54420 0
t.weickert@neura.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
EmbaseAdjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial.2024https://dx.doi.org/10.1016/j.bbi.2023.10.012
N.B. These documents automatically identified may not have been verified by the study sponsor.