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Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?

Primary Purpose

Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Status
Unknown status
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Raloxifene Hydrochloride
Placebo
Sponsored by
The Alfred
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Mental Illness, SERM, Raloxifene

Eligibility Criteria

18 Years - 45 Years (Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Physically well
  • DSM-IV diagnosis of schizophrenia, schizoaffective or schizophreniform
  • 18- 45 years
  • Able to give informed consent
  • PANSS total score > 60 (1 - 7 scale) and a score of 4 (moderate) or more on two or more of the following PANSS items: delusions, hallucinatory behaviour, conceptual disorganization or suspiciousness

Exclusion Criteria:

  • Patients with known abnormalities in the hypothalamo-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event.
  • Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; presence of illness causing immobilization.
  • Patients whose psychotic illness is directly related to illicit substance use or who have a history of substance abuse or dependence during the last six months, or consumption of more than 30gm of alcohol (three standard drinks) per day
  • Smoking more than 20 cigarettes per day.
  • Use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including tibolone or use of phytoestrogen supplements as powder or tablet.

Sites / Locations

  • Alfred HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Raloxifene Hydrochloride 120mg oral per day

Placebo tablet - one per day

Arm Description

120mg raloxifene plus antipsychotic drug

Lactose pill plus antipsychotic medication

Outcomes

Primary Outcome Measures

Change from Baseline to 12 week follow up in PANSS-positive and negative syndrome scale
Positive and Negative Symptom Schedule (PANSS): The PANSS will be performed at baseline and at weeks 2,4,6,8,10 and 12. The PANSS consists of a Positive Scale (7 positive symptom constructs), a Negative Scale (7 negative symptom constructs) and a General Psychopathology Scale (16 symptom constructs). For each patient, the scale will be administered by the same trained rater. The PANSS provides a well standardised method of evaluating and monitoring psychotic symptoms. The rater is trained and recertified against an internationally recognised "gold standard".

Secondary Outcome Measures

Montgomery Asberg Depression Rating Scale (MADRS):
Montgomery Asberg Depression Rating Scale (MADRS): The MADRS will be performed at baseline, then at weeks 2,4,6,8,10 and 12. Many patients with schizophrenia have co-existing depression, hence monitoring of depression is important.
MATRICS Consensus Cognitive Battery
MATRICS Consensus Cognitive Battery (MCCB): The MATRICS test battery will be conducted at baseline and at study completion to quantify changes in cognitive functioning. This standardized battery assess the key separable cognitive deficits in schizophrenia and has a high test-retest reliability. The MATRICS comprises 7 Domains of which we will be assessing speed of processing, working memory, verbal learning, visual learning and reasoning and problem solving.
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
A neuropsychological test battery will be conducted at baseline and study completion to quantify changes in cognitive functioning. The RBANS comprises 12 subtests that are used to calculate five index scores (Immediate Memory; Visuospatial/Constructional; Language; Attention and Delayed Memory) and a total score. There are alternate forms to be used at each time point to avoid practice effects. The inclusion of the RBANS will allow direct comparisons in cognitive functioning with our other estrogen trials.

Full Information

First Posted
November 16, 2011
Last Updated
January 6, 2020
Sponsor
The Alfred
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1. Study Identification

Unique Protocol Identification Number
NCT01481883
Brief Title
Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?
Official Title
A Randomised Controlled Trial of Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 2012 (undefined)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Alfred

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of this project is to investigate the effect of Raloxifene 120mg in men with schizophrenia. This trial will adopt a 12 week randomised controlled model. Hypotheses 1: That the men receiving adjunctive selective estrogen receptor modulators (SERM) will have a significantly greater reduction in psychosis symptoms over the course of the study than men receiving adjunctive placebo. Hypotheses 2: That the men receiving adjunctive SERM will have a significantly greater improvement in cognitive function than men receiving adjunctive placebo
Detailed Description
With the recent advent of selective estrogen receptor modulators (SERMS), such as raloxifene hydrochloride, there is the potential to harness the positive estrogenic effect on central nervous system (CNS) neurotransmitter systems. While the CNS effects of raloxifene have not been fully studied, its actions are mediated through binding to estrogen receptors and can thereby regulate gene expression that is ligand, tissue or gene specific. By inference then, raloxifene would be expected to impact on dopamine and serotonin pathways in a similar fashion to unconjugated estrogen. This study aims to examine the impact of adjunctive SERM (120mg oral Raloxifene daily) treatment on the psychopathology and cognition of men with schizophrenia and related disorders

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
Keywords
Schizophrenia, Mental Illness, SERM, Raloxifene

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Raloxifene Hydrochloride 120mg oral per day
Arm Type
Experimental
Arm Description
120mg raloxifene plus antipsychotic drug
Arm Title
Placebo tablet - one per day
Arm Type
Placebo Comparator
Arm Description
Lactose pill plus antipsychotic medication
Intervention Type
Drug
Intervention Name(s)
Raloxifene Hydrochloride
Other Intervention Name(s)
Evista, Raloxifene
Intervention Description
120mg daily - 1 capsule daily for 12 week trial
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Lactose
Intervention Description
1 capsule daily for 12 week trial
Primary Outcome Measure Information:
Title
Change from Baseline to 12 week follow up in PANSS-positive and negative syndrome scale
Description
Positive and Negative Symptom Schedule (PANSS): The PANSS will be performed at baseline and at weeks 2,4,6,8,10 and 12. The PANSS consists of a Positive Scale (7 positive symptom constructs), a Negative Scale (7 negative symptom constructs) and a General Psychopathology Scale (16 symptom constructs). For each patient, the scale will be administered by the same trained rater. The PANSS provides a well standardised method of evaluating and monitoring psychotic symptoms. The rater is trained and recertified against an internationally recognised "gold standard".
Time Frame
baseline, week2, week4, week 6, week 8, week 10, week 12
Secondary Outcome Measure Information:
Title
Montgomery Asberg Depression Rating Scale (MADRS):
Description
Montgomery Asberg Depression Rating Scale (MADRS): The MADRS will be performed at baseline, then at weeks 2,4,6,8,10 and 12. Many patients with schizophrenia have co-existing depression, hence monitoring of depression is important.
Time Frame
baseline, week2, week4, week 6, week 8, week 10, week 12
Title
MATRICS Consensus Cognitive Battery
Description
MATRICS Consensus Cognitive Battery (MCCB): The MATRICS test battery will be conducted at baseline and at study completion to quantify changes in cognitive functioning. This standardized battery assess the key separable cognitive deficits in schizophrenia and has a high test-retest reliability. The MATRICS comprises 7 Domains of which we will be assessing speed of processing, working memory, verbal learning, visual learning and reasoning and problem solving.
Time Frame
Baseline, week 12
Title
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Description
A neuropsychological test battery will be conducted at baseline and study completion to quantify changes in cognitive functioning. The RBANS comprises 12 subtests that are used to calculate five index scores (Immediate Memory; Visuospatial/Constructional; Language; Attention and Delayed Memory) and a total score. There are alternate forms to be used at each time point to avoid practice effects. The inclusion of the RBANS will allow direct comparisons in cognitive functioning with our other estrogen trials.
Time Frame
Baseline, week 12

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Physically well DSM-IV diagnosis of schizophrenia, schizoaffective or schizophreniform 18- 45 years Able to give informed consent PANSS total score > 60 (1 - 7 scale) and a score of 4 (moderate) or more on two or more of the following PANSS items: delusions, hallucinatory behaviour, conceptual disorganization or suspiciousness Exclusion Criteria: Patients with known abnormalities in the hypothalamo-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event. Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; presence of illness causing immobilization. Patients whose psychotic illness is directly related to illicit substance use or who have a history of substance abuse or dependence during the last six months, or consumption of more than 30gm of alcohol (three standard drinks) per day Smoking more than 20 cigarettes per day. Use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including tibolone or use of phytoestrogen supplements as powder or tablet.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emmy Gavrilidis, BaAppSci
Phone
+61 3 9076 6913
Ext
66913
Email
emmy.gavrilidis@monash.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jayashri Kulkarni, Phd,FRANZCP
Organizational Affiliation
Monash Alfred Psychiatry Research Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jaysahri Kulkarni, Phd, FRANZCP
Phone
+61 3 9076 6924
Ext
66924
Email
j.kulkarni@alfred.org.au
First Name & Middle Initial & Last Name & Degree
Anthony De Castella, M App Sci
Phone
+61 3 90766564
Ext
66564
Email
anthony.decastella@med.monash.edu.au

12. IPD Sharing Statement

Citations:
PubMed Identifier
21062669
Citation
Kulkarni J, de Castella A, Headey B, Marston N, Sinclair K, Lee S, Gurvich C, Fitzgerald PB, Burger H. Estrogens and men with schizophrenia: is there a case for adjunctive therapy? Schizophr Res. 2011 Feb;125(2-3):278-83. doi: 10.1016/j.schres.2010.10.009. Epub 2010 Nov 9.
Results Reference
background
Links:
URL
http://www.maprc.org.au/home
Description
Centre website

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Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?

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