Bazedoxifene -Treatment for Women With Schizophrenia

Bazedoxifene - A New Selective Estrogen Receptor Modulator Treatment for Women With Schizophrenia: a Double-blind, Randomized, Placebo Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizo Affective Disorder; Schizophreniform Disorders
• Intervention / Treatment: Drug: Bazedoxifene Acetate; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anthony de Castella, Applied Scince; Phone Number: +61 390766564; Email: Anthony.decastella@monash.edu
• Study Contact Backup: Name: MAPrc; Phone Number: +61 390766564; Email: maprc@monash.edu

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Monash Alfred Psychiatry Research Centre
      • Contact: Anthony deCastella, Dip App Sci, BA, MA; Phone Number: 66554 +61 3 9076 6554; Email: anthony.decastella@monash.edu
      • Sub-Investigator: Anthony deCastella, Dip AppSci,BA,MA
      • Contact: Jayashri Kulkarni, MBBS,MPM,FRANZCP,PhD; Phone Number: +61 3 9076 6924; Email: j.kulkarni@alfred.org.au
      • Principal Investigator: Jayashri Kulkarni, MBBS,MPM,FRANZCP,PhD
      • Sub-Investigator: Emorfia Gavrilidis, BAppSci
      • Sub-Investigator: Caroline Gurvich, DPsych FCCN MAPS
      • Sub-Investigator: Natalie Thomas, PhD
      • Sub-Investigator: Abdul Hudaib, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Bazedoxifene; Oral Bazedoxifene dosed at 40 mg daily	Drug: Bazedoxifene Acetate; Oral Bazedoxifene dosed at 40 mg daily for 12 weeks
Placebo Comparator: Placebo; Identically packaged placebo capsule daily	Drug: Placebo; Identically packaged placebo capsule daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 Weeks

Collaborators and Investigators

• Sponsor: The Alfred
• Collaborators: Monash University; Monash Health

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 26, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 3, 2019

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mood Disorders; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bazedoxifene
• Other Study ID Numbers: HREC Reference 47262

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No