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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01481883
Recruitment Status : Recruiting
First Posted : November 30, 2011
Last Update Posted : January 9, 2020
Information provided by (Responsible Party):
Jayashri Kulkarni, Professor, The Alfred

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

Condition or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Schizophreniform Disorder Drug: Raloxifene Hydrochloride Drug: Placebo Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Controlled Trial of Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?
Study Start Date : January 2012
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: Raloxifene Hydrochloride 120mg oral per day
120mg raloxifene plus antipsychotic drug
Drug: Raloxifene Hydrochloride
120mg daily - 1 capsule daily for 12 week trial
Other Names:
  • Evista
  • Raloxifene

Placebo Comparator: Placebo tablet - one per day
Lactose pill plus antipsychotic medication
Drug: Placebo
1 capsule daily for 12 week trial
Other Name: Lactose

Primary Outcome Measures :
  1. Change from Baseline to 12 week follow up in PANSS-positive and negative syndrome scale [ Time Frame: baseline, week2, week4, week 6, week 8, week 10, week 12 ]
    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 :
  1. Montgomery Asberg Depression Rating Scale (MADRS): [ Time Frame: baseline, week2, week4, week 6, week 8, week 10, week 12 ]
    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.

  2. MATRICS Consensus Cognitive Battery [ Time Frame: Baseline, week 12 ]
    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.

  3. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline, week 12 ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01481883

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Contact: Emmy Gavrilidis, BaAppSci +61 3 9076 6913 ext 66913

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Australia, Victoria
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Jaysahri Kulkarni, Phd, FRANZCP    +61 3 9076 6924 ext 66924   
Contact: Anthony De Castella, M App Sci    +61 3 90766564 ext 66564   
Sponsors and Collaborators
The Alfred
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Principal Investigator: Jayashri Kulkarni, Phd,FRANZCP Monash Alfred Psychiatry Research Centre
Additional Information:
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Responsible Party: Jayashri Kulkarni, Professor, Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?, The Alfred Identifier: NCT01481883    
Other Study ID Numbers: 486/11
First Posted: November 30, 2011    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: January 2020
Keywords provided by Jayashri Kulkarni, Professor, The Alfred:
Mental Illness
Additional relevant MeSH terms:
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Psychotic Disorders
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Raloxifene Hydrochloride
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents