The Role of Estrogen in the Neurobiology of Eating Disorders

Eating Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03740204
• Other study ID #: 1R01MH116205
• Status: Recruiting
• Phase: Phase 2
• Start date: June 13, 2019
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Massachusetts General Hospital
• Contact: Madhusmita Misra, M.D., M.P.H.
• Phone: 617-726-5790
• Email: mmisra[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Eating Disorders
• Feeding and Eating Disorders
• Hypoestrogenemia

Intervention

Drug:
• 17-ß estradiol transdermal patches with cyclic progesterone
17-ß estradiol transdermal patches (100 mcg 17-ß estradiol/day) with cyclic progesterone (200 mg micronized progesterone daily for 12 days every month)
• Placebo patch and pill
Placebo patch and pill

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in inhibition-switching performance on the Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWIT) with 17-ß estradiol versus placebo		Baseline to 8 weeks
Primary	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-ß estradiol versus placebo		Baseline to 8 weeks
Primary	Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-ß estradiol versus placebo		Baseline to 8 weeks
Primary	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-ß estradiol versus placebo		Baseline to 12 weeks
Primary	Change in EDI-3 Drive for Thinness score (Range: 0-28; direction: Higher values indicate more pronounced drive for thinness/worse outcome) with 17-ß estradiol versus placebo		Baseline to 12 weeks
Secondary	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-ß estradiol versus placebo		Baseline to 8 weeks
Secondary	Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-ß estradiol versus placebo		Baseline to 8 weeks
Secondary	Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-ß estradiol versus placebo		Baseline to 8 weeks
Secondary	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-ß estradiol versus placebo		Baseline to 12 weeks
Secondary	Change in caloric intake by 4-day food diary with 17-ß estradiol versus placebo		Baseline to 12 weeks