The Role of Estrogen in the Neurobiology of Eating Disorders: A Study of Cognitive Flexibility and Reward in Eating Disorders

1R01MH116205

This is a randomized, double blind, placebo-controlled study of the effects of transdermal estradiol versus placebo on cognitive flexibility, reward processing, and eating disorder pathology in hypoestrogenemic female adolescents and young adults (ages 14-35 years) with an eating disorder characterized by extreme dietary restriction and/or excessive exercise. Subjects will be randomized 1:1 to 12 weeks of transdermal estradiol with cyclic progesterone or placebo patches and cyclic placebo pills. Study visits include a screening visit to determine eligibility and visits at baseline, 8 weeks, and 12 weeks. Study procedures comprise behavioral, neuroimaging, and endocrine assessments.

2019-06-13

2025-09-30

2025-12-31

Recruiting

Early phase I

120

Inclusion criteria: * Female * 14-35 years * Bone age ≥13.5 years (applicable only for participants \<16 years) * Clinically significant eating disorder characterized by restriction and/or excessive exercise and high drive for thinness * Hypoestrogenemia: Oligo-amenorrhea defined as lack of menses for ≥3 months within a 6-month period of oligomenorrhea (cycle length ≥5 weeks) or absence of menses at \>15 years if premenarchal or low estradiol levels evaluated by the study physician * Low or normal weight defined by a body mass index that is \<85th percentile for 14-18 year olds and a body mass index \<25 kg/m2 for adults Exclusion criteria: * Suicidal ideation where outpatient treatment is determined unsafe by study clinician * Other causes of oligo-amenorrhea, unless a study clinician determines that missed menstrual periods are more likely a consequence of restrictive eating * Medications that contain estrogen ± progesterone within the past 3 months * Levonorgestrel-releasing intrauterine device if subject is unable to provide two to three weekly blood samples for estradiol of if estradiol levels are determined to be too high by study doctor * Neurological or psychiatric disorders that may impact neural circuitry of interest * Lifetime history of seizure disorder or electroconvulsive therapy * Pregnancy/breastfeeding * Gastrointestinal tract surgery * Contraindications to estrogen use * Any other significant illness or condition that the investigator determines could interfere with study participation or safety or put the subject at any unnecessary risk

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 120, 'type': 'ESTIMATED'}}

2024-05-31