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

Study Overview
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Brief Summary
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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
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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

Official Title
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A Randomised Controlled Trial of Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?

Conditions
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Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Intervention / Treatment
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* Drug: Raloxifene Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raloxifene Hydrochloride 120mg oral per day<br>120mg raloxifene plus antipsychotic drug | Drug: Raloxifene Hydrochloride<br>* 120mg daily - 1 capsule daily for 12 week trial<br>* Other names: Raloxifene;|
| Placebo Comparator: Placebo tablet - one per day<br>Lactose pill plus antipsychotic medication | Drug: Placebo<br>* 1 capsule daily for 12 week trial<br>* Other names: Lactose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline, week2, week4, week 6, week 8, week 10, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline, week2, week4, week 6, week 8, week 10, week 12 | 
| 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. | Baseline, week 12 | 
| 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. | Baseline, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Mental Illness, SERM, Raloxifene