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Trial registered on ANZCTR


Registration number
ACTRN12608000461392
Ethics application status
Approved
Date submitted
29/08/2008
Date registered
16/09/2008
Date last updated
20/08/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical Trial of a Selective Estrogen Receptor Modulator (raloxifene) in Schizophrenia
Scientific title
Clinical Trial of a Selective Estrogen Receptor Modulator (raloxifene) in the treatment of cognitive deficits and psychotic symptoms of patients with schizophrenia
Secondary ID [1] 698 0
Nil
Universal Trial Number (UTN)
Trial acronym
CASSI study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cognitive deficits in patients with schizophrenia 3623 0
psychotic symptoms in patients with schizophrenia 3624 0
Condition category
Condition code
Mental Health 3784 3784 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
raloxifene at a daily oral intake dose of 120 mg/day. A thirteen week double-blind, cross-over design will be used in which patients will receive either raloxifene or placebo as an adjunctive treatment to their previously stabilized antipsychotic medication. Following treatment in the first 6-week phase, patients will then enter a one week wash-out before entering the second 6-week phase consisting of the alternate treatment (raloxifene or placebo). Thus, in total, participants will be treated with raloxifene for a period of 6 weeks.
Intervention code [1] 3334 0
Treatment: Drugs
Comparator / control treatment
placebo (lactose) pill administered orally.
Control group
Placebo

Outcomes
Primary outcome [1] 4678 0
Verbal Fluency Controlled Oral Word Association Test
Timepoint [1] 4678 0
baseline, week 6, week 13
Primary outcome [2] 4679 0
verbal immediate and delayed story recall Wechlser Memory Scale III
Timepoint [2] 4679 0
baseline, week 6, week 13
Primary outcome [3] 4680 0
working memory Letter-Number Sequencing Wechsler Adult Intelligence Scale III
Timepoint [3] 4680 0
baseline, week 6, week 13
Secondary outcome [1] 7898 0
positive and negative symptoms assessed using Positive and Negative Symptom Scale (PANSS) scores
Timepoint [1] 7898 0
baseline, week 6, week 13

Eligibility
Key inclusion criteria
Male and female patients with schizophrenia between the ages of 18 and 45 who have been receiving any antipsychotic medication for at least one year can participate.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any patients with a psychiatric diagnosis other than schizophrenia or a history of substance dependence (within past 5 years), head injuries with loss of consciousness, seizures, central nervous system infection, diabetes, hypertension, lactose intolerance, superficial thrombophlebitis (pain and inflammation in a vein just under the skin), thromboembolic disease (blood clotting disease), congestive heart failure, or who have had reactions to raloxifene will be excluded.

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)
Participants were enrolled and allocated a participant number obtained from Prince of Wales Hospital Pharmacy which controlled the randomization schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e., computerised sequence generation).
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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
ANOVA, t-tests, cluster analyses. The number of participants was determined on the basis of a power analysis. The number of participants would be large enough to detect an effect of treatment alone, however, the larger sample size was required to detect an effect of treatment on the basis of ESR1 genotype and diagnosis which would reduce the numbers in each of the groups.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 1446 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 1121 0
2031
Recruitment postcode(s) [2] 1122 0
2035

Funding & Sponsors
Funding source category [1] 3799 0
University
Name [1] 3799 0
University of New South Wales
Address [1] 3799 0
Barker Street
Randwick NSW 2031
Country [1] 3799 0
Australia
Funding source category [2] 3800 0
Charities/Societies/Foundations
Name [2] 3800 0
Schizophrenia Research Institute
Address [2] 3800 0
384 Victoria Street
Darlinghurst NSW 2010
Country [2] 3800 0
Australia
Funding source category [3] 287804 0
Government body
Name [3] 287804 0
National Health and Medical Research Council
Address [3] 287804 0
16 Marcus Clarke Street
Canberra, ACT2601
Country [3] 287804 0
Australia
Funding source category [4] 287805 0
Government body
Name [4] 287805 0
New South Wales Ministry of Health
Address [4] 287805 0
Locked Mail Bag 961
North Sydney, NSW 2059
Country [4] 287805 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
Sydney, NSW 2052
Country
Australia
Secondary sponsor category [1] 3409 0
University
Name [1] 3409 0
University of New South Wales
Address [1] 3409 0
Barker Street
Randwick NSW 2031
Country [1] 3409 0
Australia
Secondary sponsor category [2] 3410 0
Other
Name [2] 3410 0
Prince of Wales Medical Research Institute
Address [2] 3410 0
Barker and Easy Streets
Randwick NSW 2031
Country [2] 3410 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5857 0
University of New South Wales Human Research Ethics Committee [HREC]
Ethics committee address [1] 5857 0
Barker Street
Randwick NSW 2031
Ethics committee country [1] 5857 0
Australia
Date submitted for ethics approval [1] 5857 0
10/05/2007
Approval date [1] 5857 0
09/08/2007
Ethics approval number [1] 5857 0
UNSW HREC 07121
Ethics committee name [2] 5858 0
South East Sydney Illawarra Area Health Service Human Research Ethics Committee [HREC]
Ethics committee address [2] 5858 0
Avoca Street
Randwick NSW 2031
Ethics committee country [2] 5858 0
Australia
Date submitted for ethics approval [2] 5858 0
30/10/2007
Approval date [2] 5858 0
23/07/2008
Ethics approval number [2] 5858 0
SESIAHS HREC 07/259
Ethics committee name [3] 289754 0
Adelaide Health Service
Ethics committee address [3] 289754 0
11 Hindmarsh Square, Adelaide, SA 5000
Ethics committee country [3] 289754 0
Australia
Date submitted for ethics approval [3] 289754 0
07/07/2011
Approval date [3] 289754 0
15/09/2011
Ethics approval number [3] 289754 0
2010188

Summary
Brief summary
The objectives of this study are to determine the extent to which 1) a hormone intervention therapy will reduce psychotic symptoms and improve cognitive function in patients with schizophrenia, 2) genetic changes in the oestrogen receptor alpha gene can be used to predict cognitive improvement in patients with schizophrenia, and 3) hormone intervention therapy will modify brain activation as assessed by functional Magnetic Resonance Imaging in patients with schizophrenia. Our hypotheses are: 1) adjunctive administration of a selective estrogen receptor modulator (SERM) will improve clinical symptoms and estrogen-sensitive cognitive deficits exhibited by patients with schizophrenia, 2) common variation in the oestrogen receptor alpha gene will predict the degree of cognitive improvement with SERM treatment in patients with schizophrenia, 3) adjunctive SERM treatment will modify dysfunctional brain activity during a cognitive test in patients with schizophrenia, and 4) that the altered SERM related dorsolateral prefrontal activity will be related to specific oestrogen receptor alpha genotypes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28885 0
Dr Thomas Weickert
Address 28885 0
Neuroscience Research Australia
Barker Street
Randwick, NSW 2031
Country 28885 0
Australia
Phone 28885 0
02 9399 1730
Fax 28885 0
02 9399 1034
Email 28885 0
t.weickert@unsw.edu.au
Contact person for public queries
Name 12042 0
Dr Thomas Weickert
Address 12042 0
Neuroscience Research Australia
Barker Street
Randwick, NSW 2031
Country 12042 0
Australia
Phone 12042 0
02 9399 1730
Fax 12042 0
02 9399 1034
Email 12042 0
t.weickert@unsw.edu.au
Contact person for scientific queries
Name 2970 0
Dr Thomas Weickert
Address 2970 0
Neuroscience Research Australia
Barker Street
Randwick, NSW 2031
Country 2970 0
Australia
Phone 2970 0
02 9399 1730
Fax 2970 0
02 9399 1034
Email 2970 0
t.weickert@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary