None listed
Conditions
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.
Interventions
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
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
16 Years to 60 Years
Healthy volunteers
No
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.
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).
Outcome results
None listed