Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000897662
Ethics application status
Approved
Date submitted
1/08/2023
Date registered
21/08/2023
Date last updated
28/04/2024
Date data sharing statement initially provided
21/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Estradiol for the treatment of anorexia nervosa
Scientific title
A double-blinded randomised placebo-controlled trial of estradiol: investigating the effect on disordered eating symptoms of women with anorexia nervosa
Secondary ID [1] 310265 0
none
Universal Trial Number (UTN)
Trial acronym
E-TAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
anorexia nervosa 330945 0
Condition category
Condition code
Mental Health 327755 327755 0 0
Eating disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Description of intervention(s) / exposure: Estradiol transdermal patch (estradot)
The dose administered: 50mcg per patch.
The mode of administration: patches will be replaced twice weekly (every 3-4 days)
The duration of administration: 12 weeks
Intervention code [1] 326642 0
Treatment: Drugs
Comparator / control treatment
Placebo - opsite flexifix adhesive roll
Control group
Placebo

Outcomes
Primary outcome [1] 335553 0
The Change in Eating Disorder Symptoms scale (CHEDS)
CHEDS assesses change in eating disorder symptoms during treatment.
Timepoint [1] 335553 0
Baseline vs. 12 weeks post-commencement of treatment (Visit 5)
Secondary outcome [1] 424935 0
Change in Body Mass Index (height determined by stadiometer, and weight determined using balance scales)
Timepoint [1] 424935 0
Baseline vs 12 weeks post-commencement of treatment (Visit 5)

Eligibility
Key inclusion criteria
1. Diagnosis of AN (restrictive or binge-eating/purging subtype), in accordance with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5).
2. 16 years or older in age.
3. Baseline body mass index (BMI) above 14
4. No initiation of therapies targeting AN within the 4 weeks prior to screening. This includes pharmacological and psychological therapies.
5. No increase or initiation of medications with appetite suppressing and/or weight loss effects within the 4 weeks prior to screening.
6. Demonstrated capacity to give informed consent
7. Participants who are engaged with an existing clinical treatment team for their AN at the time of enrolment and over the course of trial participation. For this purpose, engagement is defined as maintaining clinical contact, on average, at least every 4 weeks.
8. Consent for the research team to communicate with the participant’s clinical treatment team regarding a) their progress through the trial and b) communicate clinical deterioration and risks to allow facilitation of appropriate management, where clinically indicated.
Minimum age
16 Years
Maximum age
60 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to provide informed consent.
2. Hospitalisation within the 2 months prior to screening for the purpose of weight restoration or treatment of other medical instability that has a causal link to AN.
3. Physical parameters meeting Criteria for Medical Ward Admission as per the Alfred Health Eating Disorder – Inpatient Access and Treatment Pathways Guideline, namely:
a. High refeeding risk;
b. Vital signs as follows:
i. Systolic BP < 80 mmHg;
ii. Postural BP drop > 20 mmHg systolic, > 10 mmHg diastolic
iii. Heart rate < 40 or > 110;
iv. Temperature < 35.5oC
c. Blood tests within the preceding 7 days showing:
i. Blood glucose <3.0 mmol/L
ii. Serum sodium <130 mmol/L
iii. Serum magnesium <0.6 mmol/L
iv. Serum potassium <3.0 mmol/L
v. Serum phosphate <0.7 mmol/L
vi. Glomerular filtration rate < 60 ml/min (Cockroft-Gault)
vii. Albumin <27 g/L
viii. Liver enzymes ALT > 3 x upper limit of normal
ix. Neutrophils <1.0x109/L
d. GCS <15
4. Known history of breast, endometrial or ovarian cancer (individual, mother, or maternal grandmother)
5. Women aged 40 or over who have not had a normal mammogram in the last 24 months
6. Abnormal pap smear in the last 24 months
7. History of blood clots (e.g., deep vein thrombosis, pulmonary embolism)
8. Previous arterial thromboembolic disease (e.g., stroke)
9. Diagnosed with Type I diabetes, hyperthyroidism, Crohn’s disease or other conditions that reduce weight
10. Taking greater than or equal to 3 psychotropics
11. Other clinically significant cardiac, respiratory, renal, or endocrine conditions, or evidence of medical instability, at the discretion of the investigator
12. Concomitant neurological disorder or a history of a seizure disorder
13. Any contraindication to estrogen
14. Participants who are pregnant or lactating
15. Current substance use meeting DSM-5 criteria for severe substance use disorder
16. Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder, or delusional disorder as assessed by the SCID-5 at the time of screening.
17. Use of any investigational procedure (e.g., clinical trial) within 30 days prior to randomisation. In case of exposure to an investigational medicinal product, investigator must ensure that it is adequately washed out prior to randomisation (at least 30 days or 5 half-lives of the investigational medicinal product, whatever is longer).

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)
- sealed opaque envelopes
- allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/10/2023
Actual
18/04/2024
Date of last participant enrolment
Anticipated
19/09/2026
Actual
Date of last data collection
Anticipated
19/12/2026
Actual
Sample size
Target
50
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 25302 0
Monash Alfred Psychiatry Research Centre - Melbourne
Recruitment postcode(s) [1] 40975 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 314472 0
University
Name [1] 314472 0
Monash University
Country [1] 314472 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Wellington Rd, Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 316425 0
None
Name [1] 316425 0
Address [1] 316425 0
Country [1] 316425 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313523 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 313523 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 313523 0
Australia
Date submitted for ethics approval [1] 313523 0
24/07/2023
Approval date [1] 313523 0
09/01/2024
Ethics approval number [1] 313523 0

Summary
Brief summary
Anorexia nervosa (AN) is a serious psychiatric condition with high morbidity and mortality, for which existing treatment paradigms demonstrate suboptimal therapeutic efficacy and duration of treatment effect. Convergent lines of evidence point to the use of estradiol as a pharmacological treatment option for AN. Through restoring hormonal imbalances, estradiol can address many domains of AN including mood and cognition, bone density, and appetite regulation. The proposed study aims to investigate whether estradiol is more effective in reducing symptoms of AN than placebo. Previous studies in bone health have found significant bone mineral density improvements at 100mcg/day and 40mcg/day, however, no study to date has investigated the use of estradiol to address mood and cognition. Based on our clinical work, we propose to use 50mcg transdermal estradiol patch.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128438 0
Prof Jayashri Kulkarni
Address 128438 0
Monash Alfred Psychiatry Research Centre
Level 4 607 St Kilda Road
Melbourne 3004 VIC
Country 128438 0
Australia
Phone 128438 0
+61390766924
Fax 128438 0
Email 128438 0
jayashri.kulkarni@monash.edu
Contact person for public queries
Name 128439 0
Dr Eveline Mu
Address 128439 0
Monash Alfred Psychiatry Research Centre
Level 4 607 St Kilda Road
Melbourne 3004 VIC
Country 128439 0
Australia
Phone 128439 0
+61390766589
Fax 128439 0
Email 128439 0
eveline.mu@monash.edu
Contact person for scientific queries
Name 128440 0
Dr Eveline Mu
Address 128440 0
Monash Alfred Psychiatry Research Centre
Level 4 607 St Kilda Road
Melbourne 3004 VIC
Country 128440 0
Australia
Phone 128440 0
+61390766589
Fax 128440 0
Email 128440 0
eveline.mu@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual data (de-identified) for the primary and secondary outcomes
When will data be available (start and end dates)?
Available for 5 years after publication
Available to whom?
Upon email request to Principal Investigator
Available for what types of analyses?
Any
How or where can data be obtained?
Via email (jayashri.kulkarni@monash.edu) request to the Principal Investigator


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.