Clinical trial NCT01481883: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Keywords: Schizophrenia
Mental Illness
SERM
Raloxifene
Lead sponsor: The Alfred
Sponsor class: OTHER
First posted: 2011-11-30
Enrollment: 13
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Change from Baseline to 12 week follow up in PANSS-positive and negative syndrome scale
timeFrame: baseline, week2, week4, week 6, week 8, week 10, week 12
Secondary outcomes:
measure: Montgomery Asberg Depression Rating Scale (MADRS):
timeFrame: baseline, week2, week4, week 6, week 8, week 10, week 12
measure: MATRICS Consensus Cognitive Battery
timeFrame: Baseline, week 12
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
timeFrame: Baseline, week 12
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
Study officials:
affiliation: Monash Alfred Psychiatry Research Centre
name: Jayashri Kulkarni, Phd,FRANZCP
role: PRINCIPAL_INVESTIGATOR
References:
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.