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Trial registered on ANZCTR


Registration number
ACTRN12617001317381p
Ethics application status
Not yet submitted
Date submitted
10/08/2017
Date registered
13/09/2017
Date last updated
13/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Estrogen vs Progesterone for the treatment of Borderline Personality Disorder
Scientific title
A Randomised Placebo Controlled Trial of Estradiol vs Progesterone 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 100mcg twice weekly patch or 100mg micronized oral progesterone daily or placebo, as an adjunct to treatment as usual, for 12 weeks (84 days). Participants will be asked about adherence and a patch count will be completed at every visit after baseline.
Intervention code [1] 298854 0
Treatment: Drugs
Comparator / control treatment
Placebo Group/ patch
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 (day 0), 14 days, 28 days, 42 days, 56 days, 70 days, 84 days.
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] 338454 0
To measure potential change iin the Assessment of Quality of Life (AQoL) scores.
Timepoint [3] 338454 0
Day 0, Day 84.
Secondary outcome [4] 338455 0
To measure potential change in Dissociative Experience Scales (DES), a 28-question self-reported assessment for multi-modulatory experiences of dissociation.
Timepoint [4] 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
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
– Known, suspected or history of breast, endometrial or ovarian cancer, or
known or suspected estrogen-dependent neoplasia
– Current pregnancy, lactation or use of hormone therapies for
contraception or other purposes
– Chronic inflammatory or autoimmune disease (e.g. arthritis, lupus)
– Unexplained vaginal bleeding
– Peri/ post menopause (either naturally or through surgical intervention)
– Liver dysfunction or disease
– History of blood clots (e.g. deep vein thrombosis, pulmonary embolism)
– Previous arterial thromboembolic disease (e.g. stroke)
– Lifetime diagnosis of schizophrenia, schizoaffective disorder,
substance-induced psychotic disorder, major depression with psychosis,
bipolar I disorder (DSM-5) as measured by SCID-5.
– Risk of suicide such that inpatient admission is required, as determined
by PI Kulkarni (psychiatrist) based on the presence of suicidal behaviour (ZAN-BPD self-mutilation/suicidality subscale) and clinical assessment.
– Taking more than 4 psychotropic medications
– New/ planned changes to psychotropic medication/psychotherapy plans
– Substance abuse or dependence in last 3 months
– Smoking more than 20 cigarettes per day
– Recent (less than or equal to 3 months) traumatic life events measured by the Holmes-Rahe
Life Stress Inventory

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 drug encapsulation, perform 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 1:1:1 block randomisation to be allocated to one of the three 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 drug encapsulation, perform 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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
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
Address [1] 297259 0
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
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
Not yet submitted
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
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 three arm trial of i.) 100mcg estradiol patch vs ii) 100mg micronized progesterone vs iii.) placebo (in addition to treatment as usual), in a total of 60 women with BPD (20 per arm).
Primary Aim: To determine if the addition of estradiol or progesterone will lead to a significant improvement in clinical symptoms of BPD, as defined by The Borderline Personality Disorder Severity Index (BPDSI-IV), when compared to placebo.
Primary Hypothesis: The addition of estradiol and/or progesterone will lead to a significant improvement in clinical symptoms of BPD, defined as a decrease of more than or equal to 11.7 points on the Borderline Personality Disorder Severity Index (BPDSI-IV), compared to placebo.
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
Dr Natalie Thomas
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
natalie.thomas@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

No data has been provided for results reporting
Summary results
Not applicable