[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT03740204":3,"trial-entities:NCT03740204":120,"trial-summary:NCT03740204":124},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":21,"study_type":31,"primary_purpose":32,"phases":33,"enrollment_info":35,"interventions":38,"primary_outcomes":49,"secondary_outcomes":62,"sex":73,"minimum_age":74,"maximum_age":75,"healthy_volunteers":76,"eligibility_criteria":77,"std_ages":97,"locations":100,"central_contacts":109,"overall_officials":110,"references":114,"see_also_links":119},"NCT03740204","1R01MH116205","The Role of Estrogen in the Neurobiology of Eating Disorders","The Role of Estrogen in the Neurobiology of Eating Disorders: A Study of Cognitive Flexibility and Reward in Eating Disorders","ACTIVE_NOT_RECRUITING","2026-12-31","2026-05","2026-05-29","2019-06-13","Massachusetts General Hospital","OTHER",true,"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\u002For 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.",null,[19,20],"Eating Disorders","Hypoestrogenemia",[22,23,24,25,26,19,27,28,29,20,30],"Adolescent","Amenorrhea","Anorexia Nervosa","Cognitive Flexibility","Dietary Restriction","Estrogen","Excessive Exercise","Females","Reward","INTERVENTIONAL","TREATMENT",[34],"PHASE2",{"count":36,"type":37},120,"ACTUAL",[39,45],{"type":40,"name":41,"description":42,"armGroupLabels":43},"DRUG","17-β estradiol transdermal patches with cyclic progesterone","17-β estradiol transdermal patches (100 mcg 17-β estradiol\u002Fday) with cyclic progesterone (200 mg micronized progesterone daily for 12 days every month)",[44],"17-β estradiol with cyclic progesterone",{"type":40,"name":46,"description":46,"armGroupLabels":47},"Placebo patch and pill",[48],"Placebo",[50,53,55,57,60],{"measure":51,"timeFrame":52},"Change in inhibition-switching performance on the Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWIT) with 17-β estradiol versus placebo","Baseline to 8 weeks",{"measure":54,"timeFrame":52},"Change in Temporal Experience of Pleasure Scale (TEPS) Consummatory Pleasure score (Range: 8-48; direction: Higher values indicate more pronounced consummatory pleasure\u002Fbetter outcome) with 17-β estradiol versus placebo",{"measure":56,"timeFrame":52},"Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo",{"measure":58,"timeFrame":59},"Change in Eating Disorder Inventory-3 (EDI-3) Body Dissatisfaction score (Range: 0-36; direction: Higher values indicate more pronounced body dissatisfaction\u002Fworse outcome) with 17-β estradiol versus placebo","Baseline to 12 weeks",{"measure":61,"timeFrame":59},"Change in EDI-3 Drive for Thinness score (Range: 0-28; direction: Higher values indicate more pronounced drive for thinness\u002Fworse outcome) with 17-β estradiol versus placebo",[63,65,67,69,71],{"measure":64,"timeFrame":52},"Change in functional magnetic resonance imaging (fMRI) activation of the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) during a task switching paradigm with 17-β estradiol versus placebo",{"measure":66,"timeFrame":52},"Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-β estradiol versus placebo",{"measure":68,"timeFrame":52},"Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-β estradiol versus placebo",{"measure":70,"timeFrame":59},"Change in the Eating Disorder Examination (EDE) Dietary Restraint subscale (Range: 0-6; direction: Higher values indicate more pronounced dietary restraint\u002Fworse outcome) with 17-β estradiol versus placebo",{"measure":72,"timeFrame":59},"Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo","FEMALE","14 Years","35 Years",false,{"inclusion":78,"exclusion":85,"raw_text":96},[79,80,81,82,83,84],"Female","14-35 years","Bone age ≥13.5 years (applicable only for participants \\\u003C16 years)","Clinically significant eating disorder characterized by restriction and\u002For 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 \\\u003C85th percentile for 14-18 year olds and a body mass index \\\u003C25 kg\u002Fm2 for adults",[86,87,88,89,90,91,92,93,94,95],"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\u002Fbreastfeeding","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","Inclusion criteria:\n\n* Female\n* 14-35 years\n* Bone age ≥13.5 years (applicable only for participants \\\u003C16 years)\n* Clinically significant eating disorder characterized by restriction and\u002For excessive exercise and high drive for thinness\n* 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\n* Low or normal weight defined by a body mass index that is \\\u003C85th percentile for 14-18 year olds and a body mass index \\\u003C25 kg\u002Fm2 for adults\n\nExclusion criteria:\n\n* Suicidal ideation where outpatient treatment is determined unsafe by study clinician\n* Other causes of oligo-amenorrhea, unless a study clinician determines that missed menstrual periods are more likely a consequence of restrictive eating\n* Medications that contain estrogen ± progesterone within the past 3 months\n* 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\n* Neurological or psychiatric disorders that may impact neural circuitry of interest\n* Lifetime history of seizure disorder or electroconvulsive therapy\n* Pregnancy\u002Fbreastfeeding\n* Gastrointestinal tract surgery\n* Contraindications to estrogen use\n* 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",[98,99],"CHILD","ADULT",[101],{"facility":13,"city":102,"state":103,"zip":104,"country":105,"geoPoint":106},"Boston","Massachusetts","02114","United States",{"lat":107,"lon":108},42.35843,-71.05977,[],[111],{"name":112,"affiliation":13,"role":113},"Madhusmita Misra, M.D., M.P.H.","PRINCIPAL_INVESTIGATOR",[115],{"pmid":116,"type":117,"citation":118},"40294815","DERIVED","Breithaupt L, Slattery M, Lauze M, Petterway F, Lindman L, Cravitz M, Naticchia S, Seenivasa S, Powers M, Javaras KN, Alperovitz DJ, Halperin J, Dechant E, Thomas JJ, Lawson EA, Lee H, Pizzagalli DA, Romer AL, Kumar P, Plessow F, Misra M, Eddy KT. Study protocol for a randomized, placebo-controlled, double-masked mechanistic clinical trial of transdermal estrogen replacement in hypoestrogenic eating disorders to explore the role of estrogen on cognitive flexibility and reward processing. Contemp Clin Trials. 2025 Jul;154:107924. doi: 10.1016\u002Fj.cct.2025.107924. Epub 2025 Apr 26.",[],{"nct_id":4,"conditions":121,"biomarkers":123},[24,122],"Eating Disorder",[],{"nct_id":4,"found":76,"summary":17,"prompt_version":17}]