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The Role of Estrogen in the Neurobiology of Eating Disorders

Primary Purpose

Eating Disorders, Hypoestrogenemia

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

17-β estradiol transdermal patches with cyclic progesterone

Placebo patch and pill

About this trial

This is an interventional treatment trial for Eating Disorders focused on measuring Adolescent, Amenorrhea, Anorexia Nervosa, Cognitive Flexibility, Dietary Restriction, Eating Disorders, Estrogen, Excessive Exercise, Females, Hypoestrogenemia, Reward

Eligibility Criteria

14 Years - 35 Years (Child, Adult)FemaleDoes not accept 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

Sites / Locations

Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

17-β estradiol with cyclic progesterone

Placebo

Arm Description

Outcomes

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

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

Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo

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

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

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

Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-β estradiol versus placebo

Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-β estradiol versus placebo

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

Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo

Full Information

NCT ID

NCT03740204

First Posted

November 5, 2018

Last Updated

June 2, 2023

Sponsor

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03740204

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 13, 2019 (Actual)

Primary Completion Date

September 30, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Eating Disorders, Hypoestrogenemia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

17-β estradiol with cyclic progesterone

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

17-β estradiol transdermal patches with cyclic progesterone

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo patch and pill

Intervention Description

Placebo patch and pill

Primary Outcome Measure Information:

Title

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

Time Frame

Baseline to 8 weeks

Title

Time Frame

Baseline to 8 weeks

Title

Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo

Time Frame

Baseline to 8 weeks

Title

Time Frame

Baseline to 12 weeks

Title

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

Time Frame

Baseline to 12 weeks

Secondary Outcome Measure Information:

Title

Time Frame

Baseline to 8 weeks

Title

Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-β estradiol versus placebo

Time Frame

Baseline to 8 weeks

Title

Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-β estradiol versus placebo

Time Frame

Baseline to 8 weeks

Title

Time Frame

Baseline to 12 weeks

Title

Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo

Time Frame

Baseline to 12 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

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

Phone

617-726-5790

mmisra@mgh.harvard.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Franziska Plessow, Ph.D.

Phone

617-726-3870

fplessow@mgh.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

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

Phone

617-726-5790

mmisra@mgh.harvard.edu

First Name & Middle Initial & Last Name & Degree

Franziska Plessow, Ph.D.

Phone

617-726-3870

fplessow@mgh.harvard.edu

12. IPD Sharing Statement

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The Role of Estrogen in the Neurobiology of Eating Disorders

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