Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001317381
Ethics application status
Approved
Date submitted
10/08/2017
Date registered
13/09/2017
Date last updated
17/04/2024
Date data sharing statement initially provided
18/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Estrogen for the treatment of Borderline Personality Disorder
Scientific title
A Randomised Placebo Controlled Trial of Estradiol for the Treatment of Women with Borderline Personality Disorder
Secondary ID [1] 292628 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Borderline Personality Disorder 304345 0
Condition category
Condition code
Mental Health 303678 303678 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Female participants, aged 18-43, will be randomised to receive transdermal estradiol 1.5mg daily gel or placebo gel, as an adjunct to treatment as usual, for 12 weeks (84 days). Participants will be asked about adherence that will be completed at every study visit.
Intervention code [1] 298854 0
Treatment: Drugs
Comparator / control treatment
Placebo Group/ gel
Control group
Placebo

Outcomes
Primary outcome [1] 303043 0
The Primary Outcome will be the mean change over time in the Borderline Personality Disorder Severity Index (BPDSI-IV) from baseline (Visit 1) over the 84 day treatment period.
Timepoint [1] 303043 0
Baseline and Day 84
Primary outcome [2] 303258 0
Proportion of participants in each group achieving clinical improvement defined by a decrease of equal to or more than 11.7 points on the Borderline Personality Disorder Severity Index (BPDSI-IV).
Timepoint [2] 303258 0
Baseline, Day 84.
Secondary outcome [1] 337760 0
To measure potential change in emotional regulation assessed by 'The Difficulties in Emotion Regulation Scale' ; a 36 item scale that assesses ways that emotions are experienced, approached and processed.
Timepoint [1] 337760 0
Baseline, 84 days.
Secondary outcome [2] 338125 0
To measure potential change in cognitive and affective empathy, assessed by The Multifaceted Empathy Test (MET).
Timepoint [2] 338125 0
Baseline, Day 84
Secondary outcome [3] 338455 0
To measure potential change in Dissociative Experience Scales (DES), a 28-question self-reported assessment for multi-modulatory experiences of dissociation.
Timepoint [3] 338455 0
Day 0, Day 84.

Eligibility
Key inclusion criteria
– Age 18-43 years
– Female
– Primary diagnosis of BPD, assessed by the Diagnostic Interview for Borderline Patients (DIB-R)
– Be willing to use appropriate barrier contraceptive precaution for the duration of the study
Minimum age
18 Years
Maximum age
43 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Known history of breast, endometrial or ovarian cancer
Women aged 40 or over who have not had a normal mammogram in the last 24 months
Abnormal pap smear in the last 24 months
Contraindications to estradiol
Current pregnancy or trying to become pregnant,
History of blood clots (e.g. deep vein thrombosis, pulmonary embolism)
Previous arterial thromboembolic disease (e.g. stroke)
Acute, high risk of suicide such that inpatient admission is required, as determined by PI Kulkarni (psychiatrist) based on her expert clinical assessment.
Taking more than 5 psychotropic medications
Taking OCP that do not have 20, 30 or 35mcg estradiol component
New/ planned changes to psychotropic medication/psychotherapy plans
Consistent, severe substance abuse in last 3 months
Smoking more than 20 cigarettes per day


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)
The Alfred Clinical Trials Pharmacy will perform trial randomisation, allocate and dispense treatment. Study participants and research staff will remain blind to the intervention. A designated senior staff member who is not involved in the conduct of the study will facilitate unblinding due to any adverse event. Participants will receive notification of their results after the study is completed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants who pass screening will be assigned by a computer generated 2:1 block randomisation to be allocated to one of the study arms
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
The Alfred Clinical Trials Pharmacy will perform trial randomisation, allocate and dispense treatment. Study participants and research staff will remain blind to the intervention. A designated senior staff member who is not involved in the conduct of the study will facilitate unblinding due to any adverse event. Participants will receive notification of their results after the study is completed.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The longitudinal main outcomes will be analysed using generalised estimating equations in an intention to treat manner (SPSS statistical software).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
13/01/2020
Actual
11/11/2022
Date of last participant enrolment
Anticipated
30/04/2025
Actual
Date of last data collection
Anticipated
31/07/2024
Actual
Sample size
Target
72
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8755 0
Monash Alfred Psychiatry Research Centre - Melbourne
Recruitment hospital [2] 8756 0
The Alfred - Prahran
Recruitment postcode(s) [1] 16875 0
3004 - Melbourne
Recruitment postcode(s) [2] 16876 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 297259 0
Other
Name [1] 297259 0
Monash Alfred Psychiatry Research Centre
Country [1] 297259 0
Australia
Primary sponsor type
Hospital
Name
Alfred Hospital
Address
Commercial Rd
Melbourne Victoria, 3004
Country
Australia
Secondary sponsor category [1] 296231 0
University
Name [1] 296231 0
Monash University
Address [1] 296231 0
Wellington Road, Clayton Victoria 3800
Country [1] 296231 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298376 0
Alfred Human Research and Ethics Committee
Ethics committee address [1] 298376 0
Old Baker Building, Level 1,
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 298376 0
Australia
Date submitted for ethics approval [1] 298376 0
26/09/2017
Approval date [1] 298376 0
10/01/2019
Ethics approval number [1] 298376 0

Summary
Brief summary
Overview & Rationale: Borderline Personality Disorder (BPD) is a serious and highly prevalent (5.9%) psychiatric disorder. BPD sufferers experience severe emotional instability, social and occupational dysfunction, and engage in chronic self-mutilation and suicidal behaviours, with associated high levels of mortality, morbidity, and health service use. BPD patients are a complex group that are challenging to treat. Current psychological treatments are expensive and difficult for BPD patients to access, and there is currently no clearly designated pharmacotherapy. Underpinned by psychosocial causes, the pathogenesis of BPD is only now beginning to be understood. Childhood trauma is reported in most patients (>80%) and is linked to abnormalities in the development of the hypothalamus-pituitary-adrenal stress axis and, consequently, abnormalities in the hypothalamus-pituitary-gonadal axis. Both neuroendocrine axes have been reported as abnormal in BPD, indicating the neuroendocrine system as a potential therapeutic target for BPD symptoms. Significantly, cyclical fluctuations in ovarian hormones affect emotional and cognitive behaviours relevant to BPD.
We propose to conduct a 12-week, double blind, placebo controlled two arm trial of i.) transdermal estradiol gel 2 pumps (1 pump =1.25mg gel = 0.75mg estradiol, total = 1.5mg daily estradiol) vs ii.) placebo inactive gel 2 pumps daily (in addition to treatment as usual), in a total of 72 women with BPD/CPTSD (48 for the estradiol arm and 24 for the placebo arm) over 12 weeks.
Primary Aim: To determine whether estradiol is effective in treating symptoms of BPD/CPTSD.
Secondary Aims: To determine if estradiol has effect on specific BPD/CPTSD symptom domains including: a) social - emotional regulation; b) cognition, including memory, decision making and executive functioning; c) concomitant mood and quality of life; and d) biological markers
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76878 0
Prof Jayashri Kulkarni
Address 76878 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
Country 76878 0
Australia
Phone 76878 0
+61 3 9076 6564
Fax 76878 0
Email 76878 0
jayashri.kulkarni@monash.edu
Contact person for public queries
Name 76879 0
Ms Emorfia Gavrilidis
Address 76879 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
Country 76879 0
Australia
Phone 76879 0
+61 3 90766564
Fax 76879 0
Email 76879 0
emmy.gavrilidis@monash.edu
Contact person for scientific queries
Name 76880 0
Prof Jayashri Kulkarni
Address 76880 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
Country 76880 0
Australia
Phone 76880 0
+61 3 9076 6564
Fax 76880 0
Email 76880 0
jayashri.kulkarni@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.