Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
10 participants
INTERVENTIONAL
2020-02-24
2022-04-04
Brief Summary
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Detailed Description
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The objective of this study is to examine the direct and mechanistic role of E2 and P4 on binge eating in women with bulimia nervosa (BN; n = 15). The experimental design parallels an established design developed to determine the hormonal triggers of premenstrual dysphoric disorder and depression: temporarily stopping the menstrual cycle using a Gonadotropin-releasing hormone (GnRH) agonist (Lupron) and addback E2 and P4 independently in a double-blind crossover design. The overarching hypothesis is that BN represents a hormone-sensitive phenotype, and this sensitivity is modulated by E2's effects on aspects of the reward response such that reward-motivated behaviors increase in the context of low E2. This line of research will provide direction for future research addressing neuroendocrine, neurobiological, and brain activity and function in BN. To date, there are no medications that have been developed specifically for the treatment of individuals with BN.
Our specific aims are to:
Aim 1: Quantify the direct effect of E2 and P4 on binge eating in women with BN.
Aim 2: Determine the effect of E2 on reward response in women with BN.
Aim 3: Examine the association between reward response and binge eating before and after E2 addback.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
BASIC_SCIENCE
DOUBLE
Study Groups
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Sequence A: estradiol followed by progesterone
Participants are randomly assigned to treatment Sequence A: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence A will receive estradiol addback first, followed by progesterone.
Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks.
Estradiol
During estradiol administration, 2mg of estradiol is given twice daily via oral capsule.
Micronized progesterone
During progesterone administration, 200mg of progesterone is given twice daily via oral capsule.
Leuprolide Acetate
Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months.
Placebo Oral Capsule
Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication.
Sequence B: progesterone followed by estradiol
Participants are randomly assigned to treatment Sequence B: after achieving hormone suppression using Lupron, participants begin the addback period and take study medications for 8 weeks. During the 8 week period, participants will take placebo or estradiol or progesterone. Participants will not know when or for how long they are on active medication (i.e., estradiol or progesterone) or inactive (i.e., placebo) medication. When active medication is administered, participants randomized to treatment sequence B will receive progesterone first followed by estradiol.
Estradiol and progesterone are never given simultaneously. Participants are on active medication for a total of 4 weeks.
Estradiol
During estradiol administration, 2mg of estradiol is given twice daily via oral capsule.
Micronized progesterone
During progesterone administration, 200mg of progesterone is given twice daily via oral capsule.
Leuprolide Acetate
Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months.
Placebo Oral Capsule
Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication.
Interventions
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Estradiol
During estradiol administration, 2mg of estradiol is given twice daily via oral capsule.
Micronized progesterone
During progesterone administration, 200mg of progesterone is given twice daily via oral capsule.
Leuprolide Acetate
Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months.
Placebo Oral Capsule
Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* A regular menstrual cycle for at least three months
* \< 35 BMI \> 18.5
* Free of medication or medical condition that impacts ovarian hormones or is contraindicated for use with study interventions (including birth control pills)
* Speaks English
Exclusion Criteria
* peanut allergy
* bipolar or psychotic disorder;
* current substance use disorder or frequent binge drinking behavior;
* frequent diuretic or laxative use, ipecac use;
* currently smoking \> 10 cigarettes daily;
* history of a suicide attempt or current suicidal ideation;
* endometriosis;
* abnormal genital/vaginal bleeding;
* undiagnosed enlargement of the ovaries;
* liver disease;
* breast cancer;
* personal history of blood clots (a history of blood clots in the legs or lungs; DVT); pregnancy related blood clots
* history of seizures or epilepsy;
* porphyria;
* diabetes mellitus;
* malignant melanoma;
* gallbladder or pancreatic disease;
* heart or kidney disease;
* cerebrovascular disease (stroke);
* history of osteoporosis or osteopenia;
* recurrent migraine with aura;
* first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol;
* Refusal to use non-hormonal contraception throughout study;
* Pregnant women will be excluded from participation (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods), and women who become pregnant (although unlikely because of the hormone manipulation) will be withdrawn;
* Any condition or symptoms considered by the study team to detrimentally impact subject safety.
18 Years
42 Years
FEMALE
No
Sponsors
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National Institute of Mental Health (NIMH)
NIH
University of North Carolina, Chapel Hill
OTHER
Responsible Party
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Principal Investigators
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Jessica Baker, PhD
Role: PRINCIPAL_INVESTIGATOR
University of North Carolina, Chapel Hill
Locations
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University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Countries
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References
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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19-2343
Identifier Type: -
Identifier Source: org_study_id
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