The Role of Estrogen in the Neurobiology of Eating Disorders

NCT03740204 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 1R01MH116205
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Eating Disorders; Hypoestrogenemia

Keywords

Adolescent; Amenorrhea; Anorexia Nervosa; Cognitive Flexibility; Dietary Restriction; Eating Disorders; Estrogen; Excessive Exercise; Females; Hypoestrogenemia; Reward

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (5)

• 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

Study Arms (2)

17-β estradiol with cyclic progesterone

EXPERIMENTAL

Drug: 17-β estradiol transdermal patches with cyclic progesterone

Placebo

PLACEBO COMPARATOR

Drug: Placebo patch and pill

Interventions

17-β estradiol transdermal patches with cyclic progesterone DRUG

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

17-β estradiol with cyclic progesterone

Placebo patch and pill DRUG

Placebo patch and pill

Placebo

Eligibility Criteria

• Age: 14 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Female
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Feeding and Eating Disorders; Amenorrhea; Anorexia Nervosa

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Menstruation Disturbances; Pathologic Processes

Study Officials

• Madhusmita Misra, M.D., M.P.H.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madhusmita Misra, M.D., M.P.H.

CONTACT

617-726-5790; abp6bd@uvahealth.edu

Kamryn Eddy, Ph.D.

CONTACT

617-724-1744; keddy@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Chief, Pediatric Endocrinology

Study Record Dates

• First Submitted: November 5, 2018
• First Posted: November 14, 2018
• Study Start: June 13, 2019
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

US (1)