Evaluation of Estradiol Transdermal Patch in Adolescent Females with Anorexia Nervosa: An Open-Label Pilot Study

The primary objective of this study is to evaluate the **efficacy** and feasibility of **estrogen replacement therapy** (ERT) on psychological and physiological symptoms in adolescent girls with **anorexia nervosa**. This pilot study aims to determine whether ERT can lead to an improvement in anorectic symptoms, which could potentially justify a subsequent full-scale randomized placebo-controlled trial. The clinical relevance of this study lies in its potential to introduce a new treatment option for anorexia nervosa, utilizing a drug that is already available on the market for other indications. The successful implementation of ERT in clinical practice could enhance treatment strategies for patients with anorexia nervosa.

The clinical trial focuses on evaluating the efficacy and feasibility of estrogen replacement therapy in girls diagnosed with **anorexia nervosa**. The study population comprises exclusively female participants, specifically targeting an age range that corresponds to adolescents. The trial does not include male subjects, and the participants are not considered a vulnerable population. The selection criteria for the trial include patients with anorexia nervosa, as well as those with anorexia accompanied by anxiety and depression. The sponsor has not provided information regarding the total number of participants involved in the study. Lifestyle considerations such as diet, physical activity, or habits have not been specified in the available data. The trial aims to assess the potential benefits of estrogen replacement therapy on both psychological and physiological symptoms associated with anorexia nervosa.

The clinical trial is designed to evaluate the **efficacy** and feasibility of **estrogen replacement therapy** in adolescent females diagnosed with **anorexia nervosa**. This is a Phase 4, open-label pilot study, which will serve as a precursor to a potential full-scale randomized placebo-controlled trial, contingent upon the outcomes of this initial investigation. The trial is set to commence recruitment on April 4, 2022, and is anticipated to conclude by April 4, 2025. The investigational product, Estradot 50 micrograms/24 hours transdermal patch, containing the active substance **estradiol**, will be administered via cutaneous use.

Participants will be involved in the study for a maximum treatment period of 13 weeks. The study will include several key visits: an initial screening visit to confirm eligibility based on the inclusion criteria, which require participants to have anorexia nervosa, potentially with concomitant anxiety and depression. Follow-up visits will be scheduled to monitor the primary endpoints, which include anxiety levels measured by STAI-C and specific symptoms of anorexia assessed by the EDE-Q. Secondary endpoints will evaluate cortisol, ghrelin, T3, T4 levels, weight gain, cognitive performance, and Beck Youth Inventory scores. The end-of-study visit will assess the overall treatment efficacy and safety.

Participants may be withdrawn from the study if they experience adverse effects that compromise their safety or if they fail to adhere to the study protocol. The trial's exploratory nature aims to provide insights into the potential integration of estrogen replacement therapy into clinical practice for treating anorexia nervosa, leveraging a drug already approved for other indications. The study's findings will inform the feasibility of conducting a larger-scale trial to further validate the therapeutic approach.

The clinical trial involves the administration of **Estradiol** as the experimental medication. The pharmaceutical form of the medication is a **transdermal patch**, specifically marketed under the name "Estradot 50 mikrog/24 timer depotplaster." The active substance, **Estradiol**, is of chemical origin and is also known by synonyms such as **Estradiol Anhydrous**, **Oestradiol**, **Oestradiol-17-Beta**, and **17Beta-Estradiol**. The transdermal patch is designed for **cutaneous use**, delivering a maximum daily dose of 50 micrograms. The total maximum dose over the treatment period is 4550 micrograms. The treatment duration is set for a maximum period of 13 weeks. The patch is applied to the skin, allowing for the gradual release of the medication into the bloodstream.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the **Estradiol** transdermal patch. Participant compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol. The study aims to evaluate the efficacy and feasibility of estrogen replacement therapy in treating adolescent anorexia nervosa, with the potential for future implementation in clinical practice if successful.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoints include the measurement of anxiety levels using the State-Trait Anxiety Inventory for Children (STAI-C) and specific symptoms of anorexia nervosa using the Eating Disorder Examination Questionnaire (EDE-Q). These tools are validated scales that provide quantitative data on psychological symptoms associated with anorexia nervosa.

Secondary endpoints will involve the assessment of various physiological and cognitive parameters. These include the measurement of **cortisol**, **ghrelin**, **T3**, and **T4** levels, which are biomarkers relevant to the physiological state of patients with anorexia nervosa. Additionally, weight gain will be monitored as an indicator of physical health improvement. Cognitive performance will be evaluated using the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test II (CVLT II), while psychological well-being will be further assessed using the Beck Youth Inventory scores.

The collection and analysis of these efficacy parameters will be conducted at specified timepoints throughout the trial, although the exact schedule is not detailed in the provided data. The trial is designed as a Phase 4 therapeutic exploratory study, testing the efficacy and feasibility of estrogen replacement therapy in adolescent girls with anorexia nervosa. The study aims to provide insights into the potential benefits of this treatment approach, with the possibility of advancing to a full-scale randomized placebo-controlled trial if the pilot study demonstrates positive outcomes.