Transdermal Estrogen in Women With Anorexia Nervosa

Study Overview
=================
Brief Summary
-----------------
Randomized, placebo-controlled study investigating the use of physiologic, transdermal estrogen for low bone mass in adult women with anorexia nervosa.

Detailed Description
-----------------
Anorexia nervosa is a prevalent psychiatric with a lifetime prevalence of up to 2.2%. Among the many medical co-morbidities associated with anorexia nervosa, the most common is significant bone loss, which can persist despite weight recovery. Nearly 90% of women with anorexia nervosa have osteopenia and this low bone mass is associated with an increased fracture risk. Nearly 30% of women with anorexia nervosa report a history of a fracture and a prospective study demonstrated a 7-fold increased risk of fracture in women with anorexia nervosa compared to age-matched controls. Because anorexia nervosa is a chronic disease that can persist despite psychiatric and nutritional counseling, the bone loss and increased fracture risk can persist and lead to lifelong morbidity. Therefore, finding a treatment for bone loss associated with anorexia nervosa is of critical importance. This 18-month randomized, placebo-controlled study will investigate in women (ages 20 to 45 years old) with anorexia nervosa whether treatment with transdermal estrogen replacement will increase bone mineral density (BMD).

Official Title
-----------------
Transdermal Estrogen for the Treatment of Bone Loss in Women With Anorexia Nervosa

Conditions
-----------------
Anorexia Nervosa

Intervention / Treatment
-----------------
* Drug: Transdermal estrogen
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female 19-45 years of age DSM-5 psychiatric criteria for anorexia nervosa <85% of ideal body weight as defined by the 1983 Metropolitan Life Insurance Height and Weight Tables Amenorrhea T-score of < -1.0 at spine or hip Exclusion Criteria: Diseases known to affect bone metabolism, including untreated thyroid dysfunction, vitamin D deficiency, Cushing's syndrome, diabetes mellitus or renal insufficiency (eGFR < 60) Personal history of venous or arterial clot History of stroke or myocardial infarction History of hypercoagulable disorder Personal history or history of a first-degree relative with breast cancer History of hereditary angioedema Any medication known to affect bone metabolism, including systemic glucocorticoids within three months of the baseline visit, depot medroxyprogesterone within 6 months of the baseline visit, oral bisphosphonates within one year of the baseline visit or IV bisphosphonates within three years of the baseline visit Bone fracture within the prior 12 months Serum potassium < 3.0 meq/L, serum ALT > 3 times the upper limit of normal or Hemoglobin < 10 g/dL Fasting serum triglyceride level > 150 mg/dL Pregnant or breastfeeding (or desiring pregnancy within the next 18 months) Active substance abuse Elevated PTH level 25-OH vitamin D level < 20 ng/mL Low phosphorus level

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transdermal estrogen/progesterone<br>Transdermal estradiol (0.045mg)/levonorgestrel (0.015mg) patch applied weekly for 18 months | Drug: Transdermal estrogen<br>* Transdermal estradiol (0.045mg)/levonorgestrel (0.015mg) weekly patch<br>|
| Placebo Comparator: Placebo<br>Placebo patch applied weekly for 18 months | Drug: Placebos<br>* Placebo weekly patch<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bone mineral density at 18 months | Change in lumbar spine bone mineral density at 18 months | Baseline, 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bone mineral density at hip at 18 months | Change in total hip bone mineral density at 18 months | Baseline, 18 months | 
| Change in bone mineral density at femoral neck at 18 months | Change in femoral neck bone mineral density at 18 months | Baseline, 18 months | 
| Change in parameters of bone microarchitecture at 18 months | Change in microarchitectural parameters as measured by high-resolution peripheral quantitative CT at 18 months | Baseline, 18 months | 
| Change in estimated bone strength at 18 months | Change in estimated bone strength as assessed by finite element analysis at 18 months | Baseline, 18 months | 
| Change in vertebral fractures at 18 months | Change in vertebral fractures as assessed by vertebral fracture assessment at 18 months | Baseline, 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bone mineral density, Estrogen