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

The Alfred

Status and phase: Completed; Phase 4

Conditions: Schizophreniform Disorder; Schizophrenia; Schizoaffective Disorder

Treatments: Drug: Placebo; Drug: Raloxifene Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT01481883

486/11

Details and patient eligibility

About

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

Full 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

Enrollment: 13 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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13 participants in 2 patient groups, including a placebo group

Raloxifene Hydrochloride 120mg oral per day

Experimental group

Description:

120mg raloxifene plus antipsychotic drug

Treatment:

Drug: Raloxifene Hydrochloride

Placebo tablet - one per day

Placebo Comparator group

Description:

Lactose pill plus antipsychotic medication

Treatment:

Drug: Placebo