Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001015932
Ethics application status
Approved
Date submitted
18/06/2020
Date registered
7/10/2020
Date last updated
25/04/2024
Date data sharing statement initially provided
7/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Double-Blind Randomised Investigation of Bazedoxifene and Conjugated Estrogen for Depression in Menopausal Women
Scientific title
Double-Blind Randomised Investigation of Bazedoxifene and Conjugated Estrogen for Depression in Menopausal Women
Secondary ID [1] 301560 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 317924 0
Menopause 317925 0
Condition category
Condition code
Mental Health 315960 315960 0 0
Depression
Mental Health 315962 315962 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To compare, in a twelve-week double-blind randomised controlled trial, the psychological and physical outcomes of women experiencing a first-onset, relapse or persistent depressive symptoms that commenced during the peri-menopause in four groups: i) women taking Bazedoxifene and conjugated estrogen (20mg/0.30mg oral/day) in adjunct to standard antidepressant treatment, ii) women taking placebo in adjunct to standard antidepressant treatment, iii) women taking Bazedoxifene and conjugated estrogen (20mg/0.30mg oral/day), iv) women taking placebo alone (i.e. women not using any psychotropic / hormone treatment).
20mg Bazedoxifene (Conbriza) / 0.30 mg Conjugated Estrogen (Premarin)
Dose: 0.30 mg Conjugated Estrogen and 20mg Bazedoxifene daily for 12 weeks.
Duration: 12 weeks.
Mode: Modified release Tablet
Adherence: Medication adherence will be assessed fortnightly. Empty bottles will be collected by the study coordinator and questions include detailing any missed tablets, and questioning how many bottles/pills are leftover - responses are recorded.
Intervention code [1] 317859 0
Treatment: Drugs
Comparator / control treatment
Placebo lactose capsugels.
Control group
Placebo

Outcomes
Primary outcome [1] 324175 0
MONTGOMERY-ASBERG DEPRESSION RATING SCALE (MADRS)
Timepoint [1] 324175 0
Mean change from Baseline to Week 12 after intervention commencement
Secondary outcome [1] 383914 0
MENQOL-I (The Menopause-specific Quality of Life (MENQOL) Questionnaire)
Timepoint [1] 383914 0
Comparing Baseline to Week 12 after intervention commencement
Secondary outcome [2] 383915 0
SF36 (Medical outcomes study - 36 Item Short form Survey)
A 36 item self-report measure that assesses: physical health and bodily pain; vitality, social functioning; role limitations due to emotional problems; and mental health
Timepoint [2] 383915 0
Comparing Baseline to Week 12 after intervention commencement
Secondary outcome [3] 383916 0
SSS (Sabbatsberg Self-Rating Scale)
Sabbatsberg Sexual Self Rating Scale (SSS) is a 21 item self-report questionnaire covering seven domains: sexual interest, arousal, satisfaction with sexual life, experience of sexual pleasure, fantasy, orgasmic capacity, and sexual relevancy
Timepoint [3] 383916 0
Comparing Baseline to Week 12 after intervention commencement.
Secondary outcome [4] 383917 0
Eye-Movement Tracking data
An emotional Antisaccade task will be included to explore attentional control over emotions. Eye movements will be recorded using The EyeLink II (SR Research Ltd). This system consists of three miniature cameras mounted on a padded headband. Two eye cameras allow binocular eye tracking. An optical head-tracking camera integrated into the headband allows accurate tracking of the subject’s point of gaze without the need for a bite bar. Participants will be seated in a dark room, facing a computer screen. They are requested by the assessor to fixate and/or shifting their gaze in response to a number of stimuli, appearing on the screen. Three 2-5 minute tasks of increasing levels of cognitive demand will be included. The first two tasks will involve a green target cross and include a prosaccade task (involve visually guided reflexive saccades) and an Antisaccade task (where participants are required to look in the mirror location of a presented target). The third task will be an emotional Antisaccade task, which will be identical to the previous Antisaccade task; however in place of the green target cross will be emotive pictures.
Timepoint [4] 383917 0
Comparing Baseline to Week 12 after intervention commencement
Secondary outcome [5] 383918 0
Biological Factor Measurement of blood RNA expression levels (exploratory aim). 40 ml of blood will be collected at bl, 6, 12. Whole blood will be collected using a PAXgene Blood RNA Tube intended for immediate stabalisation of intracellular RNA, and stored frozen at -80C until analysis
Timepoint [5] 383918 0
Repeated measure analysis will be performed at timepoints BL, 6, and 12, comparing intervention and placebo groups over time.
Secondary outcome [6] 386149 0
Biological Factor Measurement of blood serum (exploratory aim). 40 ml of blood will be collected at bl, 6, 12. Whole lood will be collected, processed and serum will be stored frozen at -80C until analysis
Timepoint [6] 386149 0
Repeated measure analysis will be performed at timepoints BL, 6, and 12, comparing intervention and placebo groups over time.
Secondary outcome [7] 386150 0
Biological Factor Measurement of blood plasma (exploratory aim). 40 ml of blood will be collected at bl, 6, 12. Whole blood will be collected, processed and plasma will be stored frozen at -80C until analysis
Timepoint [7] 386150 0
Repeated measure analysis will be performed at timepoints BL, 6, and 12, comparing intervention and placebo groups over time.
Secondary outcome [8] 386151 0
Biological Factor Measurement of saliva (exploratory aim). Saliva samples will be collected at bl, 6, 12. Saliva will be stored frozen at -80C until analysis
Timepoint [8] 386151 0
Repeated measure analysis will be performed at timepoints BL, 6, and 12, comparing intervention and placebo groups over time.

Eligibility
Key inclusion criteria
Females who are currently physically well

Current DSM-IV diagnosis of depression disorder

Able to give informed consent

Menopausal as determined by standardized classification guidelines for female reproductive ageing were proposed at the Stages of Reproductive (STRAW).

First-onset or relapse of depression during menopause

Currently taking either an SSRI or SNRI, or no psychotropic medication at all

Evidence of a normal mammogram in the preceding 24 months.

Documented normal Pap smear and pelvic examination in the preceding two years.

English language proficiency (in order to provide informed consent and complete cognitive test battery)
Minimum age
40 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key 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, breast pathology, undiagnosed vaginal bleeding or abnormal Pap smear results.
• Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; or the presence of illness causing immobilisation.
• Patients experiencing severe melancholia, neurovegetative symptoms or current suicidality necessitating acute hospitalisation or intensive psychiatric treatment.
• 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).
• Patients with psychotic symptoms or past history of severe mental illness including schizophrenia, and bipolar disorder.
• Women aged 40 or over who have not had a normal mammogram in the last 24 months
• Current use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including Bazedoxifene or use of phytoestrogen supplements as powder or tablet
• Pregnancy / Lactation
• Smoking cigarettes, >4 standard drinks of ETOH per day, illicit drug dependence.
• Planned changes to psychotropic medication or psychotherapy regimen.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Blinding and medication dispensing are independently performed for this trial by The Alfred Clinical Trials Pharmacy. When the medication is dispensed by The Alfred Clinical Trials Pharmacy, they provide the study coordinator with a sealed, opaque blinding envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Each patient will be allocated an identification number and randomly assigned to a treatment regimen according to a computer-generated pseudo-random code. 1:1 block randomisation will be used to ensure balanced participant numbers in both arms
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Using multilevel modelling with an expected effect size of 0.3, five time points and intra-class correlation of 00.25, the total sample size would be 138 (69 in each group) to reach a power of 79.5%.

Analysis will be conducted on participants who complete 1) at least one post-baseline treatment visit (intention to treat) and 2) per protocol to provide a measure of the reliability of the primary analysis. We will estimate the average change in MADRS scores over 12 weeks in each treatment arm. The primary efficacy measure is the change in MADRS scores from baseline to end of treatment. Secondary analysis of MENQOL-I, SF36, SSS data, eye-tracking results, and biological factor measurements comparing baseline to 12 weeks will be done. To further explore the extent to which non-treatment factors (e.g., sleep, vasomotor symptoms) and circulating hormone fluctuations are associated with changes in mood; hierarchical linear regression will be conducted with change from baseline to week 12 in MADRS scores as the dependent variable, and baseline hormone, PSQI, SSS and MENQOL-I levels as possible predictors. We will do a subgroup analysis of those treated with an SSRI versus SNRI. Analyses for trials conducted by our centre, including the proposed trial, draw strongly on the expertise of staff from the Department of Epidemiology and Preventive Medicine at The Alfred

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/10/2020
Actual
15/12/2020
Date of last participant enrolment
Anticipated
30/04/2025
Actual
Date of last data collection
Anticipated
30/07/2025
Actual
Sample size
Target
90
Accrual to date
38
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16928 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 30586 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 305994 0
University
Name [1] 305994 0
Monash University
Country [1] 305994 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Wellington Rd, Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 306452 0
None
Name [1] 306452 0
Address [1] 306452 0
Country [1] 306452 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306230 0
The Alfred Ethics Committee
Ethics committee address [1] 306230 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 306230 0
Australia
Date submitted for ethics approval [1] 306230 0
03/09/2019
Approval date [1] 306230 0
13/11/2019
Ethics approval number [1] 306230 0

Summary
Brief summary
The purpose of this study is to investigate the use of the medication combination Bazedoxifene and conjugated estrogen, a hormone replacement therapy, in the treatment of depression with a first onset or relapse during the peri-menopausal phase that is still persisting.
The study will employ a 12-week, double-blind, randomised, two-arm parallel-group design. Participants will be randomised to one of two groups: (1) Daily oral Bazedoxifene and conjugated estrogen (20mg/0.30mg), (2) Placebo (sugar pill).
The aim is to compare, in a twelve-week double-blind randomised controlled trial, the psychological and physical outcomes of women experiencing a first-onset, relapse or persistent depressive symptoms that commenced during the peri-menopause in four groups: i) women taking Bazedoxifene and conjugated estrogen (20mg/0.30mg oral/day) in adjunct to standard antidepressant treatment, ii) women taking placebo in adjunct to standard antidepressant treatment, iii) women taking Bazedoxifene and conjugated estrogen (20mg/0.30mg oral/day), iv) women taking placebo alone (i.e. women not using any psychotropic / hormone treatment).
It is hypothesized that women receiving Bazedoxifene plus conjugated estrogen alone, and Bazedoxifene plus conjugated estrogen in adjunct to standard antidepressant medication will have the same as or significantly greater improvement in depressive symptoms compared with women receiving placebo in adjunct to standard SSRI and women not using any psychotropic/hormone treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103178 0
Prof Jayashri Kulkarni
Address 103178 0
Monash Alfred Psychiatry research centre
Level 4, 607 St Kilda Road, Melbourne, VIC 3004
Country 103178 0
Australia
Phone 103178 0
+61 03 9076 6564
Fax 103178 0
Email 103178 0
Jayashri.Kulkarni@monash.edu
Contact person for public queries
Name 103179 0
Emorfia Gavrilidis
Address 103179 0
Monash Alfred Psychiatry research centre
Level 4, 607 St Kilda Road, Melbourne, VIC 3004
Country 103179 0
Australia
Phone 103179 0
+61 03 9076 6564
Fax 103179 0
Email 103179 0
emmy.gavrilidis@monash.edu
Contact person for scientific queries
Name 103180 0
Caroline Gurvich
Address 103180 0
Monash Alfred Psychiatry research centre
Level 4, 607 St Kilda Road, Melbourne, VIC 3004
Country 103180 0
Australia
Phone 103180 0
+61 03 9076 6564
Fax 103180 0
Email 103180 0
Caroline.Gurvich@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.