- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00206557
The Use of Selective Estrogen Receptor Modulators in the Treatment of Schizophrenia- a Pilot Study
Study Overview
Status
Intervention / Treatment
Detailed Description
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, we 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 8 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, we have conducted a 4 week double blind, placebo controlled study using 100 microgram estradiol skin patch. We found that the 12 pre-menopausal 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. (Kulkarni et al 2000).
The major potential risks in using estrogen as a longer-term adjunctive treatment in pre-menopausal 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 we used estrogen without progesterone over an 8 week or 4 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, we are putting forward an investigator initiated clinical trial proposal to investigate the effect of adjunctive raloxifene on psychotic symptoms in women with schizophrenia.
The aim of this project is to study the effect of raloxifene as an adjunct to antipsychotic medication in postmenopausal women with schizophrenia as a means of developing a novel, safe adjunctive treatment for women with schizophrenia to improve their quality of life.
Study Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
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Victoria
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Melbourne, Victoria, Australia, 3181
- Alfred Psychiatry Research Centre, Alfred Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Female aged over 45 years
- Current diagnosis of DSM-IV Schizophrenia, Schizoaffective or Schizophreniform Disorder
- Symptom rating greater than 60 on the PANSS at baseline/screening
- Patient able to give informed consent
- Patient post menopausal (confirmed by hormone assay and Greene Climacteric Scale plus Menstrual Cycle Questionnaire)
Exclusion Criteria:
- Clinically significant concomitant medical or neurological condition or history of venous thromboembolic event
- High suicide/aggression Risk in the opinion of the investigator.
- If patient's psychotic illness is directly related to illicit substance abuse or has a history of substance abuse or dependence in the past 6 months
- Smoking more than 20 cigarettes per day
- Use of any form of hormones or hormone therapy
- Illness causing immobilisation
- Undiagnosed postmenopausal vaginal bleeding
- Consumption of more than 30gm of alcohol (3 standard drinks)per day.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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PANSS score at trial completion (12 weeks)
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Secondary Outcome Measures
Outcome Measure |
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MADRS score at trial completion (12 weeks)
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Cognitive Test scores at trial completion (12 weeks)
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Adverse Symptom Checklist score at trial completion (12 weeks)
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Hormone level change over study period (12 weeks)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jayashri Kulkarni, MBBS, MPM, FRANZCP, PHD, Bayside Health; Alfred Hospital
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Disease
- Psychotic Disorders
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Estrogens
- Hormone Antagonists
- Bone Density Conservation Agents
- Estrogen Antagonists
- Selective Estrogen Receptor Modulators
- Estrogen Receptor Modulators
- Estradiol
- Raloxifene Hydrochloride
Other Study ID Numbers
- APRC 146/02
- 03T-422
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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