search
Back to results

Bazedoxifene -Treatment for Women With Schizophrenia

Primary Purpose

Schizophrenia, Schizophreniform Disorders, Schizo Affective Disorder

Status
Recruiting
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Bazedoxifene Acetate
Placebo
Sponsored by
The Alfred
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Physically well.
  • A current DSM-V diagnosis of schizophrenia or related disorder.
  • 18- 65 years
  • Able to give informed consent.
  • PANSS total score between 40 and 90 and a score of 4 (moderate) or more on two or more of the following PANSS items: delusions, hallucinatory behaviour, conceptual disorganization or suspiciousness.
  • Documented normal PAP smear and pelvic examination in the preceding two years.
  • Stable psychotropic medication for previous 4 weeks
  • Normal breast ultrasound
  • IQ > 70 (as determined by the WAIS IV subtests)
  • English language proficiency (in order to provide informed consent and complete cognitive test battery)

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 a history of severe traumatic brain injury or significant neurological or unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; presence of illness causing immobilisation.
  • Patients whose psychotic illness is directly related to illicit substance use or who have a history of substance dependence during the last six months (with the exclusion of caffeine and/or nicotine dependence).
  • Women aged 40 or over who have not had a normal mammogram in the last 24 months
  • Use of any form of estrogen, progestin or androgen as hormonal therapy in preceding 4 weeks including the pill.
  • Pregnant (HCG will be measured at screening)
  • Breastfeeding
  • Planned changes to psychotropic medication or psychotherapy regimen.

Sites / Locations

  • Monash Alfred Psychiatry Research CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Oral Bazedoxifene

Placebo

Arm Description

Oral Bazedoxifene dosed at 40 mg daily

Identically packaged placebo capsule daily

Outcomes

Primary Outcome Measures

Schizophrenia symptoms
Symptoms of schizophrenia as measured on the Positive and Negative Symptom Scale (PANSS). Subscales: Positive, Negative, General Psychopathology. Positive scale: 7 Items, (minimum score = 7, maximum score = 49). Negative scale: 7 Items, (minimum score = 7, maximum score = 49). General Psychopathology scale:16 Items, (minimum score = 16, maximum score = 112). PANSS Total score (summed from subscales): minimum = 30, maximum = 210 For all items, higher values indicate increased symptom severity.

Secondary Outcome Measures

Cognition
The neuropsychological battery will include subtests from the following batteries: MATRICS Consensus Cognitive Battery (MCCB) comprises 7 domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving and social cognition. The Repeatable Battery for Neuropsychological Status (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. A verbal fluency task (Controlled Oral Word Association Task; COWAT), visual attention task (Trails A and B) and measures of premorbid intellect (Test of Premorbid Functioning; TOPF) will also be included. Eye tracking will be an optional extra and will be recorded using The EyeLink (SR Research Ltd). Participants will fixate and/or shift their gaze in response to a number of stimuli, appearing on the screen, as requested by the assessor.

Full Information

First Posted
June 26, 2019
Last Updated
January 6, 2020
Sponsor
The Alfred
Collaborators
Monash University, Monash Health
search

1. Study Identification

Unique Protocol Identification Number
NCT04113993
Brief Title
Bazedoxifene -Treatment for Women With Schizophrenia
Official Title
Bazedoxifene - A New Selective Estrogen Receptor Modulator Treatment for Women With Schizophrenia: a Double-blind, Randomized, Placebo Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Recruiting
Study Start Date
October 7, 2019 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Alfred
Collaborators
Monash University, Monash Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
To study the effect of adjunctive bazedoxifene - a selective estrogen receptor modulator (SERM) in a double blind, placebo-controlled adjunctive study in the treatment of women with schizophrenia. All patients receive standardized antipsychotic medication.
Detailed Description
Despite advances in the treatment of schizophrenia, pharmacotherapy remains sub- optimal, and the prognosis for many patients is poor. We have pioneered work showing that estradiol has a positive role in the treatment of psychosis symptoms and cognitive deficits seen in people with schizophrenia. However, with the longer-term work from studies such as the Women's Health Initiative (1), it has become clear that long-term use of estradiol with progesterone may have associated increased risks of breast and other cancers. Hence, we began working with the Selective Estrogen Receptor Modulator - raloxifene, which appears to be safer for longer term use with respect to the development of breast and other cancers. Building on our and others work, raloxifene used as an adjunctive treatment in schizophrenia appears to produce inconsistent and varying responses in different sub-populations; gender, menopausal status, age, drug dose and delivery mode. We now propose to conduct a double-blind, randomized, placebo controlled trial of a third generation SERM - bazedoxifene - which is 4 times more selective for the alpha than the beta oestrogen receptor subtype. Bazedoxifene appears to be safer with respect to long term use than older SERMs, has additional actions on the glucocorticoid receptor, and together this different pharmacology speculatively has greater potential than other SERMs to impact favorably on both psychosis symptoms and cognition in men and women with schizophrenia. This study will test 160 women to determine if bazedoxifene, as an adjunctive hormone modulator, is effective for positive and cognitive symptoms of schizophrenia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizophreniform Disorders, Schizo Affective Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
This randomized, double-blind, placebo-controlled, 12-week trial will be conducted at two sites- the lead site is the Monash Alfred Psychiatry research Centre in Melbourne (Investigator - Prof Jayashri KULKARNI) , and a second site in Melbourne - The Monash Medical Centre (Investigator - Prof Suresh Sundram). The trial will follow the parallel comparison design consisting of two arms over 12 weeks (treatment x time). Participants will be screened to ensure inclusion / exclusion criteria are met.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants will be randomised to receive either activie treatment or identically packaged placebo
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oral Bazedoxifene
Arm Type
Experimental
Arm Description
Oral Bazedoxifene dosed at 40 mg daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Identically packaged placebo capsule daily
Intervention Type
Drug
Intervention Name(s)
Bazedoxifene Acetate
Intervention Description
Oral Bazedoxifene dosed at 40 mg daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Identically packaged placebo capsule daily
Primary Outcome Measure Information:
Title
Schizophrenia symptoms
Description
Symptoms of schizophrenia as measured on the Positive and Negative Symptom Scale (PANSS). Subscales: Positive, Negative, General Psychopathology. Positive scale: 7 Items, (minimum score = 7, maximum score = 49). Negative scale: 7 Items, (minimum score = 7, maximum score = 49). General Psychopathology scale:16 Items, (minimum score = 16, maximum score = 112). PANSS Total score (summed from subscales): minimum = 30, maximum = 210 For all items, higher values indicate increased symptom severity.
Time Frame
12 Weeks
Secondary Outcome Measure Information:
Title
Cognition
Description
The neuropsychological battery will include subtests from the following batteries: MATRICS Consensus Cognitive Battery (MCCB) comprises 7 domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving and social cognition. The Repeatable Battery for Neuropsychological Status (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. A verbal fluency task (Controlled Oral Word Association Task; COWAT), visual attention task (Trails A and B) and measures of premorbid intellect (Test of Premorbid Functioning; TOPF) will also be included. Eye tracking will be an optional extra and will be recorded using The EyeLink (SR Research Ltd). Participants will fixate and/or shift their gaze in response to a number of stimuli, appearing on the screen, as requested by the assessor.
Time Frame
12 Weeks

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Women
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Physically well. A current DSM-V diagnosis of schizophrenia or related disorder. 18- 65 years Able to give informed consent. PANSS total score between 40 and 90 and a score of 4 (moderate) or more on two or more of the following PANSS items: delusions, hallucinatory behaviour, conceptual disorganization or suspiciousness. Documented normal PAP smear and pelvic examination in the preceding two years. Stable psychotropic medication for previous 4 weeks Normal breast ultrasound IQ > 70 (as determined by the WAIS IV subtests) English language proficiency (in order to provide informed consent and complete cognitive test battery) 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 a history of severe traumatic brain injury or significant neurological or unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; presence of illness causing immobilisation. Patients whose psychotic illness is directly related to illicit substance use or who have a history of substance dependence during the last six months (with the exclusion of caffeine and/or nicotine dependence). Women aged 40 or over who have not had a normal mammogram in the last 24 months Use of any form of estrogen, progestin or androgen as hormonal therapy in preceding 4 weeks including the pill. Pregnant (HCG will be measured at screening) Breastfeeding Planned changes to psychotropic medication or psychotherapy regimen.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anthony de Castella, Applied Scince
Phone
+61 390766564
Email
Anthony.decastella@monash.edu
First Name & Middle Initial & Last Name or Official Title & Degree
MAPrc
Phone
+61 390766564
Email
maprc@monash.edu
Facility Information:
Facility Name
Monash Alfred Psychiatry Research Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jayashri Kulkarni, MBBS,MPM,FRANZCP,PhD
Phone
+61 3 9076 6924
Email
j.kulkarni@alfred.org.au
First Name & Middle Initial & Last Name & Degree
Anthony deCastella, Dip App Sci, BA, MA
Phone
+61 3 9076 6554
Ext
66554
Email
anthony.decastella@monash.edu
First Name & Middle Initial & Last Name & Degree
Jayashri Kulkarni, MBBS,MPM,FRANZCP,PhD
First Name & Middle Initial & Last Name & Degree
Anthony deCastella, Dip AppSci,BA,MA
First Name & Middle Initial & Last Name & Degree
Emorfia Gavrilidis, BAppSci
First Name & Middle Initial & Last Name & Degree
Caroline Gurvich, DPsych FCCN MAPS
First Name & Middle Initial & Last Name & Degree
Natalie Thomas, PhD
First Name & Middle Initial & Last Name & Degree
Abdul Hudaib, MBBS

12. IPD Sharing Statement

Learn more about this trial

Bazedoxifene -Treatment for Women With Schizophrenia

We'll reach out to this number within 24 hrs