The Role of Estrogen in the Neurobiology of Eating Disorders

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03740204

Collaborator

(none)

120

Enrollment

Location

Arms

51.6

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Eating Disorders Hypoestrogenemia	Drug: 17-β estradiol transdermal patches with cyclic progesterone Drug: Placebo patch and pill	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 13, 2019

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 17-β estradiol with cyclic progesterone	Drug: 17-β estradiol transdermal patches with cyclic progesterone 17-β estradiol transdermal patches (100 mcg 17-β estradiol/day) with cyclic progesterone (200 mg micronized progesterone daily for 12 days every month)
Placebo Comparator: Placebo	Drug: Placebo patch and pill Placebo patch and pill

Arm

Intervention/Treatment

Experimental: 17-β estradiol with cyclic progesterone

Drug: 17-β estradiol transdermal patches with cyclic progesterone

17-β estradiol transdermal patches (100 mcg 17-β estradiol/day) with cyclic progesterone (200 mg micronized progesterone daily for 12 days every month)

Placebo Comparator: Placebo

Drug: Placebo patch and pill

Placebo patch and pill

Outcome Measures

Primary Outcome Measures

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]
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 [Baseline to 8 weeks]
Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo [Baseline to 8 weeks]
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 [Baseline to 12 weeks]
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 [Baseline to 12 weeks]

Secondary Outcome Measures

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 [Baseline to 8 weeks]
Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-β estradiol versus placebo [Baseline to 8 weeks]
Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-β estradiol versus placebo [Baseline to 8 weeks]
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 [Baseline to 12 weeks]
Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo [Baseline to 12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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
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
Peanut allergy
Neurological or psychiatric disorders that may impact neural circuitry of interest
Lifetime history of seizure disorder or electroconvulsive therapy
Pregnancy/breastfeeding
Contraindications to MRI
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