Selective Estrogen Receptor Modulators - A Potential Treatment for Psychotic Symptoms of Schizophrenia (SERM)
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|ClinicalTrials.gov Identifier: NCT00361543|
Recruitment Status : Completed
First Posted : August 8, 2006
Last Update Posted : January 30, 2015
The aim of the project is to investigate the use of Raloxifene (a new form of estrogen) in the treatment of women with schizophrenia and schizoaffective disorder. Raloxifene is a Selective Estrogen Receptor Modulator (SERM), which means that it can affect the central nervous system (CNS) effects of estrogen (eg. improving emotional symptoms, memory, information processing and concentration), without adversely affecting reproductive tissue/organs such as breast, uterus and ovaries. The investigators are conducting a double-blind, placebo controlled, three month study comparing the psychotic symptom response of women with schizophrenia in both groups. One group will receive standard antipsychotic medication plus 120mg Raloxifene, while the second group will receive standard antipsychotic medication plus oral placebo.
Hypothesis 1: That the women receiving adjunctive Raloxifene would have a quicker recovery from psychotic symptoms, as measured on the rating scales, compared with the women receiving adjunctive placebo.
Hypothesis 2: That the Raloxifene group would have better cognitive improvement than the placebo group.
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia Schizoaffective Disorder Schizophreniform Disorder||Drug: Raloxifene hydrochloride Other: Lactose Capsules||Phase 4|
Estrogen is hypothesised to be protective for women against early onset of severe symptoms of schizophrenia (Hafner, 1991; Seeman, 1992). This 'estrogen hypothesis' was derived from epidemiological, clinical and animal studies. Following the results of such studies, the investigators conducted a study (Kulkarni et al 1996) in which a group of premenopausal women with schizophrenia were given 0.02mg oral estradiol as an adjunct to antipsychotic drug treatment for eight weeks, and compared their progress with a similar group who received antipsychotic drugs only. The group receiving estrogen made a significantly more rapid recovery from acute psychotic symptoms and also reported improvement in their general health status. Subsequently, the investigators conducted a four week double-blind, placebo-controlled study, using 100mcg estradiol skin patches. The investigators found that the 12 premenopausal women who received the estradiol adjunct had a significantly lower total PANSS and BPRS score than 12 women who received placebo patches plus antipsychotic medication.
The major potential risks in using estrogen as a longer term adjunctive treatment in premenopausal women with schizophrenia appear to be the potential harmful effects of estrogen itself in its action on breast and uterine tissue. Our studies were brief for this reason, in that the investigators used estrogen without progesterone over an eight week or four week period.
With the recent advent of Selective Estrogen Receptor Modulators, in particular Raloxifene Hydrochloride, there is the potential to harness the positive estrogenic effect on CNS neurotransmitter systems without affecting breast or uterine tissue. 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 conjugated estrogen. A study (Nickleisen et al 1999) on the effect of Raloxifene on cognition in healthy, postmenopausal women found a slight increase in verbal memory performance after one month of high dose treatment, while no other differences were found after 12 months of treatment. There are no studies in women with cognitive impairment where a treatment effect would be more likely to be apparent. Similarly, there are no clinical studies to date investigating the effect of Raloxifene on psychotic symptoms. To this end, the investigators are putting forward an investigator initiated clinical trial proposal to investigate the effect of adjunctive Raloxifene on psychotic symptoms in women with schizophrenia. This is, therefore, a study to follow our Pilot Study in the same area, but with an increase of Raloxifene from 60mg to 120mg daily.
The aim of this project is to study the effect of Raloxifene as an adjunct to antipsychotic medication in women with schizophrenia as a means to developing a novel, safe adjunctive treatment for women with schizophrenia to improve their quality of life.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||54 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Selective Estrogen Receptor Modulators - A Potential Treatment for Psychotic Symptoms of Schizophrenia?|
|Study Start Date :||August 2006|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||December 2014|
U.S. FDA Resources
Active Comparator: 1
Drug: Raloxifene hydrochloride
120 mg per capsule (1 tablet daily)
Placebo Comparator: 2
Other: Lactose Capsules
1 tablet daily for 12 weeks
- PANSS score at trial completion (12 weeks) [ Time Frame: baseline, week 2,4,6,8,10,12 ]
- MADRS score at trial completion (12 weeks) [ Time Frame: baseline, week 2,4,6,8,10,12 ]
- Cognitive Test scores at trial completion (12weeks) [ Time Frame: baseline and week 12 ]
- Adverse Symptom Checklist score at trial completion (12 weeks) [ Time Frame: baseline, week 2,4,6,8,10,12 ]
- Hormone level change over study duration (12 weeks) [ Time Frame: baseline, weeks 4, 8, 12 ]
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 ClinicalTrials.gov identifier (NCT number): NCT00361543
|Monash Alfred Psychiatry Research Centre|
|Melbourne, Victoria, Australia, 3004|
|Principal Investigator:||Jayashri Kulkarni, MBBS, MPM, FRANZCP, PhD||Bayside Health, Alfred Hospital|