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The Role of Estrogen in the Neurobiology of Eating Disorders

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ClinicalTrials.gov Identifier: NCT03740204
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Madhusmita Misra, Massachusetts General Hospital

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 16-26) 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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 13, 2019
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eating Disorders

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




Primary Outcome Measures :
  1. 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 ]
  2. 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 [ Time Frame: Baseline to 8 weeks ]
  3. Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo [ Time Frame: Baseline to 8 weeks ]
  4. Change in Eating Disorder Inventory-2 (EDI-2) Body Dissatisfaction score (Range: 0-36; direction: Higher values indicate more pronounced body dissatisfaction/worse outcome) with 17-β estradiol versus placebo [ Time Frame: Baseline to 12 weeks ]
  5. Change in EDI-2 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 Measures :
  1. 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 [ Time Frame: Baseline to 8 weeks ]
  2. 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 ]
  3. 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 ]
  4. 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 [ Time Frame: Baseline to 12 weeks ]
  5. Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo [ Time Frame: Baseline to 12 weeks ]


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Ages Eligible for Study:   16 Years to 26 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Female
  • 16-26 years
  • Right-handed
  • Clinically significant eating disorder characterized by restriction and/or excessive exercise and high drive for thinness
  • Hypoestrogenemia: Oligoamenorrhea 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 weight that is <85th percentile for 16-18 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
  • DSM-5 eating disorders characterized by bingeing or purging
  • Other causes of oligo-amenorrhea
  • Medications that contain estrogen ± progesterone within the past 3 months
  • Neurological or psychiatric disorders that may impact neural circuitry of interest
  • Lifetime history of seizure disorder or electro-convulsive therapy
  • Pregnancy/breastfeeding
  • Contraindications to MRI
  • Gastrointestinal tract surgery
  • Contraindications to estrogen use
  • Psychotropic medications causing hyperprolactinemia
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03740204


Contacts
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Contact: Madhusmita Misra, M.D., M.P.H. 617-726-5790 mmisra@mgh.harvard.edu
Contact: Franziska Plessow, Ph.D. 617-726-0784 fplessow@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Madhusmita Misra, M.D., M.P.H.    617-726-5790    mmisra@mgh.harvard.edu   
Contact: Franziska Plessow, Ph.D.    617-726-0784    fplessow@mgh.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Madhusmita Misra, M.D., M.P.H. Massachusetts General Hospital

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Responsible Party: Madhusmita Misra, Division Chief, Pediatric Endocrinology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03740204     History of Changes
Other Study ID Numbers: 1R01MH116205 ( U.S. NIH Grant/Contract )
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Madhusmita Misra, Massachusetts General Hospital:
Adolescent
Amenorrhea
Anorexia Nervosa
Cognitive Flexibility
Dietary Restriction
Eating Disorders
Estrogen
Excessive Exercise
Females
Hypoestrogenemia
Reward

Additional relevant MeSH terms:
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Disease
Feeding and Eating Disorders
Pathologic Processes
Mental Disorders
Estradiol
Polyestradiol phosphate
Estrogens
Progesterone
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins