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

This study is currently recruiting participants.
Verified January 2014 by The Alfred
Sponsor:
Information provided by (Responsible Party):
Jayashri Kulkarni, Professor, The Alfred
ClinicalTrials.gov Identifier:
NCT01481883
First received: November 16, 2011
Last updated: March 21, 2014
Last verified: January 2014

November 16, 2011
March 21, 2014
January 2012
February 2015   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
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".
Change from Baseline to 4 week follow up in PANSS-positive and negative syndrome scale [ Time Frame: baseline, week2, week 4 ] [ Designated as safety issue: No ]
Positive and Negative Symptom Schedule (PANSS): The PANSS will be performed at baseline and at weeks 2 and 4. 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".
Complete list of historical versions of study NCT01481883 on ClinicalTrials.gov Archive Site
  • Montgomery Asberg Depression Rating Scale (MADRS): [ Time Frame: baseline, week2, week4, week 6, week 8, week 10, week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, week 12 ] [ Designated as safety issue: No ]
    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.
  • Montgomery Asberg Depression Rating Scale (MADRS): [ Time Frame: Baseline, week 2, week 4 ] [ Designated as safety issue: No ]
    Montgomery Asberg Depression Rating Scale (MADRS): The MADRS will be performed at baseline, then at weeks 2 and 4. Many patients with schizophrenia have co-existing depression, hence monitoring of depression is important.
  • MATRICS Consensus Cognitive Battery [ Time Frame: Baseline, week 4 ] [ Designated as safety issue: No ]
    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 standardised battery assess the key seperable 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.
Not Provided
Not Provided
 
Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?
A Randomised Controlled Trial of Selective Estrogen Receptor Modulators (SERMs) - A Potential Treatment for Psychotic Symptoms of Schizophrenia in Men?

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

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

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Schizoaffective Disorder
  • Schizophreniform Disorder
  • Drug: Raloxifene Hydrochloride
    120mg daily - 1 capsule daily for 12 week trial
    Other Names:
    • Evista
    • Raloxifene
  • Drug: Placebo
    1 capsule daily for 12 week trial
    Other Names:
    • Placebo
    • Lactose
  • Experimental: Raloxifene Hydrochloride 120mg oral per day
    120mg raloxifene plus antipsychotic drug
    Intervention: Drug: Raloxifene Hydrochloride
  • Placebo Comparator: Placebo tablet - one per day
    Lactose pill plus antipsychotic medication
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
180
June 2015
February 2015   (final data collection date for primary outcome measure)

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.
Male
18 Years to 45 Years
No
Contact: Emmy Gavrilidis, BaAppSci +61 3 9076 6913 ext 66913 emmy.gavrilidis@monash.edu
Australia
 
NCT01481883
486/11
Yes
Jayashri Kulkarni, Professor, The Alfred
The Alfred
Not Provided
Principal Investigator: Jayashri Kulkarni, Phd,FRANZCP Monash Alfred Psychiatry Research Centre
The Alfred
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP