SchizophreniaPhase 2NCT00206557
The Use of Selective Estrogen Receptor Modulators in the Treatment of Schizophrenia- a Pilot Study
A Phase 2 study testing Raloxifene and Estradiol/dyhydroprogestrone in people with Schizophrenia and Schizoaffective Disorder, run by The Alfred at 1 site in Australia.
Trial summary
The aim of the project is to investigate the use of raloxifene (a new form of estrogen) as a treatment for schizophrenia in postmenopausal women. Raloxifene is a selective estrogen receptor modulator (SERM) which means that it can affect the central nervous system effects of estrogen (eg: improving emotional symptoms… Read more about this study
- Who is it for?
- Ages 45 to 70 years, women only
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
- What is being tested?
- Raloxifene and Estradiol/dyhydroprogestrone
- How many people
- 60 participants
- Where
- 1 siteAustralia
- Study dates
- Oct 2002to Apr 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Alfred Psychiatry Research Centre, Alfred Hospital
Melbourne, Victoria, 3181
About this study
The aim of the project is to investigate the use of raloxifene (a new form of estrogen) as a treatment for schizophrenia in postmenopausal women. Raloxifene is a selective estrogen receptor modulator (SERM) which means that it can affect the central nervous system effects of estrogen (eg: improving emotional symptoms, memory, information processing and concentration), without adversely affecting reproductive tissue / organs such as breast, uterus and ovaries.We are conducting a double blind placebo controlled 3 month duration study comparing the psychotic symptom response between three groups of postmenopausal women with schizophrenia. One group will receive standard antipsychotic medication plus 60mg Raloxifene, the second group receives standard antipsychotic medication plus Hormone Therapy(estradiol 2mg oral per day + dyhydroprogesterone 10mg oral per day) and the third group receives standard antipsychotic medication plus oral placebo. Hypothesis 1: That the women receiving adjunctive raloxifene or HT 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 other two groups.
Read the 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.
- Being tested
- Raloxifene, Estradiol/dyhydroprogestrone
- Keywords
- Schizophrenia, Mental Illness, Hormone Therapy, Post-menopausal, SERM, Raloxifene
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaloxifeneDrug
Estradiol/dyhydroprogestroneDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
PANSS score at trial completion (12 weeks)
Secondary outcomes (4)
MADRS score at trial completion (12 weeks)
Cognitive Test scores at trial completion (12 weeks)
Adverse Symptom Checklist score at trial completion (12 weeks)
Hormone level change over study period (12 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startOct 2002
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 60 participants
Sponsor and investigators
- Lead sponsor
- The Alfred
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Investigators
- Jayashri Kulkarni, MBBS, MPM, FRANZCP, PHD, Principal investigator, Bayside Health; Alfred Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00206557
- Sponsor's protocol ID
- APRC 146/02
- Other IDs
- 03T-422
- Status last verified
- Apr 2007
- First submitted
- 13 Sep 2005
- Last updated
- 23 Apr 2007
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Selective Estrogen Receptor Modulators in the Treatment of Schizophrenia- a Pilot Study
- ClinicalTrials.gov ID
- NCT00206557
- Acronym / sponsor ID
- APRC 146/02
- Keywords
- Schizophrenia, Mental Illness, Hormone Therapy, Post-menopausal, SERM, Raloxifene
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants
- Lead sponsor
- The AlfredUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- Oct 2002
- Study completion
- Apr 2007 (actual)
- First posted
- 21 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the project is to investigate the use of raloxifene (a new form of estrogen) as a treatment for schizophrenia in postmenopausal women. Raloxifene is a selective estrogen receptor modulator (SERM) which means that it can affect the central nervous system effects of estrogen (eg: improving emotional symptoms, memory, information processing and concentration), without adversely affecting reproductive tissue / organs such as breast, uterus and ovaries.We are conducting a double blind placebo controlled 3 month duration study comparing the psychotic symptom response between three groups of postmenopausal women with schizophrenia. One group will receive standard antipsychotic medication plus 60mg Raloxifene, the second group receives standard antipsychotic medication plus Hormone Therapy(estradiol 2mg oral per day + dyhydroprogesterone 10mg oral per day) and the third group receives standard antipsychotic medication plus oral placebo. Hypothesis 1: That the women receiving adjunctive raloxifene or HT 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 other two groups.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 45 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Raloxifene | Drug | – |
| Estradiol/dyhydroprogestrone | Drug | – |
Primary outcome
PANSS score at trial completion (12 weeks)
4 secondary outcomes
MADRS score at trial completion (12 weeks)
Cognitive Test scores at trial completion (12 weeks)
Adverse Symptom Checklist score at trial completion (12 weeks)
Hormone level change over study period (12 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2007.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jayashri Kulkarni, MBBS, MPM, FRANZCP, PHD principal investigator
Bayside Health; Alfred Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Raloxifene and Estradiol/dyhydroprogestrone in people with Schizophrenia and Schizoaffective Disorder, run by The Alfred at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PANSS score at trial completion (12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2007.