Clinical trial NCT03740204: The Role of Estrogen in the Neurobiology of Eating Disorders
Official title: The Role of Estrogen in the Neurobiology of Eating Disorders: A Study of Cognitive Flexibility and Reward in Eating Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Eating Disorders
Hypoestrogenemia
Keywords: Adolescent
Amenorrhea
Anorexia Nervosa
Cognitive Flexibility
Dietary Restriction
Eating Disorders
Estrogen
Excessive Exercise
Females
Hypoestrogenemia
Reward
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2018-11-14
Enrollment: 120
Sex: FEMALE
Minimum age (years): 14
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline to 8 weeks
measure: Change in Temporal Experience of Pleasure Scale (TEPS) Consummatory Pleasure score (Range: 8-48; direction: Higher values indicate more pronounced consummatory pleasure/better outcome) with 17-β estradiol versus placebo
timeFrame: Baseline to 8 weeks
measure: Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo
timeFrame: Baseline to 8 weeks
measure: Change in Eating Disorder Inventory-3 (EDI-3) Body Dissatisfaction score (Range: 0-36; direction: Higher values indicate more pronounced body dissatisfaction/worse outcome) with 17-β estradiol versus placebo
timeFrame: Baseline to 12 weeks
measure: Change in EDI-3 Drive for Thinness score (Range: 0-28; direction: Higher values indicate more pronounced drive for thinness/worse outcome) with 17-β estradiol versus placebo
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: 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
timeFrame: Baseline to 8 weeks
measure: Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-β estradiol versus placebo
timeFrame: Baseline to 8 weeks
measure: Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-β estradiol versus placebo
timeFrame: Baseline to 8 weeks
measure: Change in the Eating Disorder Examination (EDE) Dietary Restraint subscale (Range: 0-6; direction: Higher values indicate more pronounced dietary restraint/worse outcome) with 17-β estradiol versus placebo
timeFrame: Baseline to 12 weeks
measure: Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Madhusmita Misra, M.D., M.P.H.
role: PRINCIPAL_INVESTIGATOR
References: