Bazedoxifene -Treatment for Women With Schizophrenia

Sponsor

The Alfred (Other)

Overall Status

Recruiting

CT.gov ID

NCT04113993

Collaborator

Monash University (Other), Monash Health (Other)

160

Enrollment

Location

Arms

50.8

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizophreniform Disorders Schizo Affective Disorder	Drug: Bazedoxifene Acetate Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Participants will be randomised to receive either activie treatment or identically packaged placebo

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 7, 2019

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Schizophrenia symptoms [12 Weeks]
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 [12 Weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria	Australia	3004

Sponsors and Collaborators

The Alfred
Monash University
Monash Health

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jayashri Kulkarni, Professor, Director of Monash Alfred Psychiatry research centre, The Alfred

ClinicalTrials.gov Identifier:

NCT04113993

Other Study ID Numbers:

HREC Reference 47262

First Posted:

Oct 3, 2019

Last Update Posted:

Jan 9, 2020

Last Verified:

Jan 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 9, 2020