CompletedNCT04225221Updated Jul 26, 2022Results posted

Neurobiology of Bulimia Nervosa

A Phase 2 interventional study of Estradiol and Micronized progesterone in Bulimia Nervosa, sponsored by University of North Carolina, Chapel Hill. Completed at 1 site in United States. Open to female participants aged 18 Years to 42 Years. Per ClinicalTrials.gov, last updated 2022-07-26.

Sponsored by University of North Carolina, Chapel Hill · Phase 2, Interventional, and Basic science

Phase: Phase 2
Study type: Interventional
Enrollment: 10
Allocation: Randomized
Ages: 18 Years to 42 Years
Sex: Female

Study summary

This pilot study experimentally manipulates ovarian hormones to examine the direct impact of estrogen (E2) and progesterone (P4) on binge eating symptom burden and the behavioral reward response in women with bulimia nervosa (n=15). This is completed by taking medications that change ovarian hormone levels. This line of research could lead to the development of pharmacological interventions developed to target specific areas of the brain, brain receptors, or pathways identified to be involved in the mechanism underlying ovarian hormone change and binge eating.

Read the detailed description

Eating disorders (EDs) affect 15 million women in the United States and have one of the highest mortality rates of any mental illness. Despite this, the underlying neurobiology remains poorly understood. EDs predominantly occur in women, and the frequency of certain symptoms change in a predictable pattern over the menstrual cycle; specifically, symptom changes appear to be triggered by normal fluctuations in the ovarian hormones estradiol (E2) and progesterone (P4).

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 studied

Bulimia Nervosa

Browse trials for

Keywords

bulimia nervosa
binge eating
eating disorder
estrogen

In context

Bulimia Nervosa

166 studies on the registry are indexed under Bulimia Nervosa; 38 are open to participants now.

This study's enrollment of 10 is below the median of 60 across 117 interventional studies indexed under Bulimia Nervosa.

Browse Bulimia Nervosa studies →

Lead sponsor

University of North Carolina, Chapel Hill is the lead sponsor of 1,366 studies on the registry; 133 are open to participants now.

Of its 158 completed or terminated interventional studies of FDA-regulated products, 139 (88%) have results posted.

Browse University of North Carolina, Chapel Hill studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 42 Years
Sexes eligible: Female
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Participants will be women aged 18-42 with a current DSM-5 bulimia nervosa (BN) diagnosis who meet the below criteria. Only participants capable of giving informed consent and understanding the risks associated with the study will be enrolled.

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

Exclusion Criteria

Patients will not be permitted to enter this protocol if they have any of the following:

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.

Study design

Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Investigator)
Enrollment: 10 participants (actual)

Study arms

Experimental
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.
Drug: Estradiol · Drug: Micronized progesterone · Drug: Leuprolide Acetate · Drug: Placebo Oral Capsule
Experimental
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.
Drug: Estradiol · Drug: Micronized progesterone · Drug: Leuprolide Acetate · Drug: Placebo Oral Capsule

Interventions

DrugEstradiol
During estradiol administration, 2mg of estradiol is given twice daily via oral capsule.
Also known as: E2, Estrace
DrugMicronized progesterone
During progesterone administration, 200mg of progesterone is given twice daily via oral capsule.
Also known as: P4, Prometrium
DrugLeuprolide Acetate
Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months.
Also known as: Lupron Depot
DrugPlacebo 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.
Also known as: Sugar pill

What researchers measure

Primary outcomes

Change in Binge Eating Sum Score
Binge eating will be measured using the 8-item binge eating subscale of the Eating Pathology Symptoms Inventory (EPSI), which measures features of binge eating (e.g., consumption of large quantities of food, mindless eating) on a 5-point Likert scale from "never" to "very often." The EPSI scale is designed to assess behavior over the past 28 days; however, to be sensitive to the timeframe of the present study, the instructions will be modified to ask participants to consider the past week. Items are summed for a scale score ranging from 0-32. Higher scores indicate more frequent experiences with binge eating behavior. Change is defined by an average change score.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention)
Change in Weekly Average Binge-eating Frequency
Binge eating frequency is based on a daily diary of self-reported binge eating frequency. Scores can range from 0 to infinity as they represent a self-reported frequency. Subjects self-report the number of binge eating episodes they had each day. Higher numbers indicate more frequent binge eating episodes. Average weekly frequency will be determined based on daily reported binge eating frequency. Change is defined by an average change score.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention)
Change in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation
Sensitivity to Punishment/Sensitivity to Reward Questionnaire will be used to measure reward sensitivity during estradiol intervention. The reward sensitivity subscale will be used, which is rated on a true/false scale with scores ranging 0-24. Higher scores indicate more sensitivity to reward. Change is defined by an average change score.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Change in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation
Time (ms) between stimulus and response will be measured during the Monetary Incentive Delay (MID) task during the win trials during the estradiol intervention. During the MID task, participants need to select the correct response during "win" and "lose" conditions by pressing a button. Higher scores indicate a longer response time to the win trials. Change is defined by an average change score.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Change in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation
During the estradiol intervention, participants will be asked to make a series of hypothetical choices between small, sooner (impulsive) vs. larger, later (self controlled) hypothetical monetary outcomes. k is a hyperbolic function with larger k values indicating more valuation of a larger delayed reward and smaller values indicating preference for more immediate, smaller rewards (more impulsivity). Change is defined as the average change in k.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Change in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation
This measures assesses individual disposition toward avoidance of activities during the estradiol intervention. The Behavioural Inhibition subscale of the Behavioural Inhibition Scale/Behavioral Activation Scale (BIS/BAS) assesses behavioural inhibition (BI) using participant self-reports. The minimum score on the BIS subscale is 7, maximum 28. Greater scores indicate greater behavioural inhibition. Change is defined by an average change score
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Change in Behavioral Activation Score During Estradiol Manipulation
This measures assesses individual disposition toward engaging in activities during the estradiol intervention. Two BIS/BAS behavioural activation (BA) subscales will be used. The BA subscales used are Fun Seeking and Drive. Each subscale is summed to get the respective subscale scores. The minimum score on BA Fun Seeking and BA Drive are minimum 4 and maximum 16. Higher scores indicate greater behavioral activation. Change is defined by an average change score.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Change in Behavioral Activation Reward Responsiveness With Estradiol Manipulation
This measures assesses individual disposition toward avoiding and engaging in activities during estradiol intervention. The BIS/BAS reward responsiveness subscale will be used. The minimum score on the BA Reward Responsiveness subscale is 5, maximum 20. Higher scores indicate greater reward responsiveness. Change is defined by an average change score.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Change in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task
Behavioral response inhibition will be examined during a go/no-go computerized task during the estradiol intervention. Inhibitory control is defined by the response accuracy of the go no/go trials. Percent of errors is calculated as the number of "go" responses on a "no/go" trial" divided by the total number of "no/go" trials." Fewer errors ("go" response on a "no/go" trial) indicates better inhibitory control. Change is defined by an average change score.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Correlation Between Change in Reward Response and Change in Binge Eating Before and During Estradiol Manipulation
Pearson correlations between change in self-reported reward response and change in binge eating between baseline and estradiol intervention will be examined. Binge eating is defined as the sum score from the Eating Pathology Symptom Inventory (EPSI). Self-reported reward response is defined as the BAS reward responsiveness subscale score and the Sensitivity to Reward/Sensitivity to Punishment Questionnaire (SPSRQ) sensitivity to reward subscale score. Change in binge eating and change in reward response between baseline and estradiol intervention was calculated and a correlation conducted between change scores.
Time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

Results

Posted Jul 26, 2022

Limitations and caveats

Due to the COVID-19 pandemic, this trial was unable to enroll the number of participants needed to complete the study leading to only a very small number of participants.

Participant flow

Lupron and Placebo Baseline (6 Weeks)

Participant flow — Lupron and Placebo Baseline (6 Weeks)
Milestone	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol
Started	6	4
Completed	5	4
Not completed	1	0

First Intervention (2 Weeks)

Participant flow — First Intervention (2 Weeks)
Milestone	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol
Started	6	4
Completed	6	4
Not completed	0	0

Washout (2 Weeks)

Participant flow — Washout (2 Weeks)
Milestone	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol
Started	5	4
Completed	4	4
Not completed	1	0

Second Intervention (2 Weeks)

Participant flow — Second Intervention (2 Weeks)
Milestone	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol
Started	5	4
Completed	5	4
Not completed	0	0

Outcome measures

PrimaryChange in Binge Eating Sum Score

Binge eating will be measured using the 8-item binge eating subscale of the Eating Pathology Symptoms Inventory (EPSI), which measures features of binge eating (e.g., consumption of large quantities of food, mindless eating) on a 5-point Likert scale from "never" to "very often." The EPSI scale is designed to assess behavior over the past 28 days; however, to be sensitive to the timeframe of the present study, the instructions will be modified to ask participants to consider the past week. Items are summed for a scale score ranging from 0-32. Higher scores indicate more frequent experiences with binge eating behavior. Change is defined by an average change score.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention)
Reported as:: Mean · score on a scale

Change in Binge Eating Sum Score
score on a scale	Estradiol	Progesterone
Change in Binge Eating Sum Score	-0.60 ± 4.7	0.89 ± 4.7

PrimaryChange in Weekly Average Binge-eating Frequency

Binge eating frequency is based on a daily diary of self-reported binge eating frequency. Scores can range from 0 to infinity as they represent a self-reported frequency. Subjects self-report the number of binge eating episodes they had each day. Higher numbers indicate more frequent binge eating episodes. Average weekly frequency will be determined based on daily reported binge eating frequency. Change is defined by an average change score.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention)
Reported as:: Mean · episodes/week

Change in Weekly Average Binge-eating Frequency
episodes/week	Estradiol	Progesterone
Change in Weekly Average Binge-eating Frequency	-0.48 ± 2.6	1.1 ± 4.7

PrimaryChange in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation

Sensitivity to Punishment/Sensitivity to Reward Questionnaire will be used to measure reward sensitivity during estradiol intervention. The reward sensitivity subscale will be used, which is rated on a true/false scale with scores ranging 0-24. Higher scores indicate more sensitivity to reward. Change is defined by an average change score.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Mean · score on a scale

Change in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation
score on a scale	Estradiol
Change in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation	-0.80 ± 1.9

PrimaryChange in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation

Time (ms) between stimulus and response will be measured during the Monetary Incentive Delay (MID) task during the win trials during the estradiol intervention. During the MID task, participants need to select the correct response during "win" and "lose" conditions by pressing a button. Higher scores indicate a longer response time to the win trials. Change is defined by an average change score.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Mean · ms

Change in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation
ms	Estradiol
Change in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation	-9.0 ± 44.0

PrimaryChange in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation

During the estradiol intervention, participants will be asked to make a series of hypothetical choices between small, sooner (impulsive) vs. larger, later (self controlled) hypothetical monetary outcomes. k is a hyperbolic function with larger k values indicating more valuation of a larger delayed reward and smaller values indicating preference for more immediate, smaller rewards (more impulsivity). Change is defined as the average change in k.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Mean · k value

Change in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation
k value	Estradiol
Change in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation	-0.0047 ± 0.011

PrimaryChange in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation

This measures assesses individual disposition toward avoidance of activities during the estradiol intervention. The Behavioural Inhibition subscale of the Behavioural Inhibition Scale/Behavioral Activation Scale (BIS/BAS) assesses behavioural inhibition (BI) using participant self-reports. The minimum score on the BIS subscale is 7, maximum 28. Greater scores indicate greater behavioural inhibition. Change is defined by an average change score

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Mean · score on a scale

Change in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation
score on a scale	Estradiol
Change in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation	0.90 ± 1.8

PrimaryChange in Behavioral Activation Score During Estradiol Manipulation

This measures assesses individual disposition toward engaging in activities during the estradiol intervention. Two BIS/BAS behavioural activation (BA) subscales will be used. The BA subscales used are Fun Seeking and Drive. Each subscale is summed to get the respective subscale scores. The minimum score on BA Fun Seeking and BA Drive are minimum 4 and maximum 16. Higher scores indicate greater behavioral activation. Change is defined by an average change score.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Mean · score on a scale

Change in Behavioral Activation Score During Estradiol Manipulation
score on a scale	Estradiol
Fun Seeking	-0.10 ± 0.88
Drive	0 ± 1.4

PrimaryChange in Behavioral Activation Reward Responsiveness With Estradiol Manipulation

This measures assesses individual disposition toward avoiding and engaging in activities during estradiol intervention. The BIS/BAS reward responsiveness subscale will be used. The minimum score on the BA Reward Responsiveness subscale is 5, maximum 20. Higher scores indicate greater reward responsiveness. Change is defined by an average change score.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Mean · score on a scale

Change in Behavioral Activation Reward Responsiveness With Estradiol Manipulation
score on a scale	Estradiol
Change in Behavioral Activation Reward Responsiveness With Estradiol Manipulation	0.10 ± 1.2

PrimaryChange in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task

Behavioral response inhibition will be examined during a go/no-go computerized task during the estradiol intervention. Inhibitory control is defined by the response accuracy of the go no/go trials. Percent of errors is calculated as the number of "go" responses on a "no/go" trial" divided by the total number of "no/go" trials." Fewer errors ("go" response on a "no/go" trial) indicates better inhibitory control. Change is defined by an average change score.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Mean · percentage of errors

Change in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task
percentage of errors	Estradiol
Change in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task	-0.094 ± 0.33

PrimaryCorrelation Between Change in Reward Response and Change in Binge Eating Before and During Estradiol Manipulation

Pearson correlations between change in self-reported reward response and change in binge eating between baseline and estradiol intervention will be examined. Binge eating is defined as the sum score from the Eating Pathology Symptom Inventory (EPSI). Self-reported reward response is defined as the BAS reward responsiveness subscale score and the Sensitivity to Reward/Sensitivity to Punishment Questionnaire (SPSRQ) sensitivity to reward subscale score. Change in binge eating and change in reward response between baseline and estradiol intervention was calculated and a correlation conducted between change scores.

Time frame:: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Reported as:: Number · Pearson correlation coefficient

Correlation Between Change in Reward Response and Change in Binge Eating Before and During Estradiol Manipulation
Pearson correlation coefficient	Estradiol
BAS Reward Responsiveness	-0.146
Sensitivity to Reward	-0.132

Adverse events

Collected over Adverse event data was tracked once participants' began receiving the Lupron and Placebo during the initial hormone suppression stage and continued through study completion (approximately 12 weeks).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Estradiol	0/10 (0%)	0/10 (0%)	5/10 (50%)
Progesterone	0/9 (0%)	0/9 (0%)	7/9 (77.8%)
Lupron and Placebo	0/10 (0%)	0/10 (0%)	10/10 (100%)

Most frequent other events

Showing 10 of 19

Most frequent other events
Event	Estradiol	Progesterone	Lupron and Placebo
Hot FlashesEndocrine disorders	3/10	4/9	6/10
SpottingReproductive system and breast disorders	0/10	0/9	5/10
HeadacheNervous system disorders	0/10	1/9	4/10
BloatingGastrointestinal disorders	1/10	0/9	3/10
DrowsinessGeneral disorders	0/10	2/9	0/10
Abdominal CrampsReproductive system and breast disorders	1/10	0/9	2/10
Breast TendernessReproductive system and breast disorders	0/10	0/9	2/10
Appetite increaseMetabolism and nutrition disorders	1/10	1/9	0/10
FatigueGeneral disorders	1/10	1/9	1/10
Temperature DysregulationGeneral disorders	0/10	1/9	0/10

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol	Total
Mean	26 ± 7.5	20 ± 1.6	24 ± 6.5

Sex: Female, Male
Sex: Female, Male(Participants)	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol	Total
Female	6	4	10
Male	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol	Total
Hispanic or Latino	1	0	1
Not Hispanic or Latino	5	4	9
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol	Total
American Indian or Alaska Native	0	0	0
Asian	1	2	3
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	0	1
White	3	2	5
More than one race	1	0	1
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(Participants)	Sequence A: Estradiol Followed by Progesterone	Sequence B: Progesterone Followed by Estradiol	Total
United States	6	4	10

Study locations

1 site

University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599, United States

References and documents

Publications

Baker JH, Girdler SS, Bulik CM. The role of reproductive hormones in the development and maintenance of eating disorders. Expert Rev Obstet Gynecol. 2012 Nov 1;7(6):573-583. doi: 10.1586/eog.12.54. PubMed 23585773 ↗
Edler C, Lipson SF, Keel PK. Ovarian hormones and binge eating in bulimia nervosa. Psychol Med. 2007 Jan;37(1):131-41. doi: 10.1017/S0033291706008956. Epub 2006 Oct 12. PubMed 17038206 ↗
Klump KL, Keel PK, Culbert KM, Edler C. Ovarian hormones and binge eating: exploring associations in community samples. Psychol Med. 2008 Dec;38(12):1749-57. doi: 10.1017/S0033291708002997. Epub 2008 Feb 29. PubMed 18307829 ↗
Lester NA, Keel PK, Lipson SF. Symptom fluctuation in bulimia nervosa: relation to menstrual-cycle phase and cortisol levels. Psychol Med. 2003 Jan;33(1):51-60. doi: 10.1017/s0033291702006815. PubMed 12537036 ↗
Price WA, Torem MS, DiMarzio LR. Premenstrual exacerbation of bulimia. Psychosomatics. 1987 Jul;28(7):378-9. doi: 10.1016/s0033-3182(87)72511-0. No abstract available. PubMed 3438453 ↗
Mac Neil BA, Hudson CC, Dempsey K, Nadkarni P. A case of symptom relapse post placement of intrauterine device (IUD) in a patient with bulimia nervosa: consequence or coincidence. Eat Weight Disord. 2017 Jun;22(2):369-372. doi: 10.1007/s40519-017-0391-z. Epub 2017 Apr 24. No abstract available. PubMed 28439806 ↗
Barth C, Villringer A, Sacher J. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Front Neurosci. 2015 Feb 20;9:37. doi: 10.3389/fnins.2015.00037. eCollection 2015. PubMed 25750611 ↗
Yoest KE, Cummings JA, Becker JB. Estradiol, dopamine and motivation. Cent Nerv Syst Agents Med Chem. 2014;14(2):83-9. doi: 10.2174/1871524914666141226103135. PubMed 25540977 ↗
Frank GK. Advances from neuroimaging studies in eating disorders. CNS Spectr. 2015 Aug;20(4):391-400. doi: 10.1017/S1092852915000012. Epub 2015 Apr 23. PubMed 25902917 ↗
Richard JE, Lopez-Ferreras L, Anderberg RH, Olandersson K, Skibicka KP. Estradiol is a critical regulator of food-reward behavior. Psychoneuroendocrinology. 2017 Apr;78:193-202. doi: 10.1016/j.psyneuen.2017.01.014. Epub 2017 Jan 28. PubMed 28214679 ↗
Klump KL, Fowler N, Mayhall L, Sisk CL, Culbert KM, Burt SA. Estrogen moderates genetic influences on binge eating during puberty: Disruption of normative processes? J Abnorm Psychol. 2018 Jul;127(5):458-470. doi: 10.1037/abn0000352. Epub 2018 Jun 21. PubMed 29927265 ↗
Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med. 1998 Jan 22;338(4):209-16. doi: 10.1056/NEJM199801223380401. PubMed 9435325 ↗
Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000 Jun;157(6):924-30. doi: 10.1176/appi.ajp.157.6.924. PubMed 10831472 ↗
Ben Dor R, Harsh VL, Fortinsky P, Koziol DE, Rubinow DR, Schmidt PJ. Effects of pharmacologically induced hypogonadism on mood and behavior in healthy young women. Am J Psychiatry. 2013 Apr;170(4):426-33. doi: 10.1176/appi.ajp.2012.12010117. PubMed 23545794 ↗
Lee EE, Nieman LK, Martinez PE, Harsh VL, Rubinow DR, Schmidt PJ. ACTH and cortisol response to Dex/CRH testing in women with and without premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian steroid replacement. J Clin Endocrinol Metab. 2012 Jun;97(6):1887-96. doi: 10.1210/jc.2011-3451. Epub 2012 Mar 30. PubMed 22466349 ↗
Nobles CJ, Thomas JJ, Valentine SE, Gerber MW, Vaewsorn AS, Marques L. Association of premenstrual syndrome and premenstrual dysphoric disorder with bulimia nervosa and binge-eating disorder in a nationally representative epidemiological sample. Int J Eat Disord. 2016 Jul;49(7):641-50. doi: 10.1002/eat.22539. Epub 2016 May 20. PubMed 27206163 ↗
Damario MA, Hammitt DG, Galanits TM, Session DR, Dumesic DA. Pronuclear stage cryopreservation after intracytoplasmic sperm injection and conventional IVF: implications for timing of the freeze. Fertil Steril. 1999 Dec;72(6):1049-54. doi: 10.1016/s0015-0282(99)00444-6. PubMed 10593380 ↗
Bourgain C, Devroey P, Van Waesberghe L, Smitz J, Van Steirteghem AC. Effects of natural progesterone on the morphology of the endometrium in patients with primary ovarian failure. Hum Reprod. 1990 Jul;5(5):537-43. doi: 10.1093/oxfordjournals.humrep.a137138. PubMed 2394784 ↗
Berman KF, Schmidt PJ, Rubinow DR, Danaceau MA, Van Horn JD, Esposito G, Ostrem JL, Weinberger DR. Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8836-41. doi: 10.1073/pnas.94.16.8836. PubMed 9238064 ↗
Bloch M, Rubinow DR, Schmidt PJ, Lotsikas A, Chrousos GP, Cizza G. Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab. 2005 Feb;90(2):695-9. doi: 10.1210/jc.2004-1388. Epub 2004 Nov 16. PubMed 15546899 ↗
Roca CA, Schmidt PJ, Deuster PA, Danaceau MA, Altemus M, Putnam K, Chrousos GP, Nieman LK, Rubinow DR. Sex-related differences in stimulated hypothalamic-pituitary-adrenal axis during induced gonadal suppression. J Clin Endocrinol Metab. 2005 Jul;90(7):4224-31. doi: 10.1210/jc.2004-2525. Epub 2005 May 10. PubMed 15886244 ↗
Schmidt PJ, Steinberg EM, Negro PP, Haq N, Gibson C, Rubinow DR. Pharmacologically induced hypogonadism and sexual function in healthy young women and men. Neuropsychopharmacology. 2009 Feb;34(3):565-76. doi: 10.1038/npp.2008.24. Epub 2008 Mar 19. PubMed 18354393 ↗
Schmidt PJ, Martinez PE, Nieman LK, Koziol DE, Thompson KD, Schenkel L, Wakim PG, Rubinow DR. Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered by Change in Ovarian Steroid Levels But Not Continuous Stable Levels. Am J Psychiatry. 2017 Oct 1;174(10):980-989. doi: 10.1176/appi.ajp.2017.16101113. Epub 2017 Apr 21. PubMed 28427285 ↗
Naessen S, Carlstrom K, Bystrom B, Pierre Y, Hirschberg AL. Effects of an antiandrogenic oral contraceptive on appetite and eating behavior in bulimic women. Psychoneuroendocrinology. 2007 Jun;32(5):548-54. doi: 10.1016/j.psyneuen.2007.03.008. Epub 2007 May 2. PubMed 17475412 ↗
Rice VC, Richard-Davis G, Saleh AA, Ginsburg KA, Mammen EF, Moghissi K, Leach R. Fibrinolytic parameters in women undergoing ovulation induction. Am J Obstet Gynecol. 1993 Dec;169(6):1549-53. doi: 10.1016/0002-9378(93)90434-k. PubMed 8267060 ↗
Misra M, Katzman DK, Estella NM, Eddy KT, Weigel T, Goldstein MA, Miller KK, Klibanski A. Impact of physiologic estrogen replacement on anxiety symptoms, body shape perception, and eating attitudes in adolescent girls with anorexia nervosa: data from a randomized controlled trial. J Clin Psychiatry. 2013 Aug;74(8):e765-71. doi: 10.4088/JCP.13m08365. PubMed 24021517 ↗
Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. N Engl J Med. 1991 Sep 12;325(11):756-62. doi: 10.1056/NEJM199109123251102. PubMed 1870648 ↗
Lukaszuk K, Liss J, Lukaszuk M, Maj B. Optimization of estradiol supplementation during the luteal phase improves the pregnancy rate in women undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril. 2005 May;83(5):1372-6. doi: 10.1016/j.fertnstert.2004.11.055. PubMed 15866571 ↗
Fatemi HM, Kolibianakis EM, Camus M, Tournaye H, Donoso P, Papanikolaou E, Devroey P. Addition of estradiol to progesterone for luteal supplementation in patients stimulated with GnRH antagonist/rFSH for IVF: a randomized controlled trial. Hum Reprod. 2006 Oct;21(10):2628-32. doi: 10.1093/humrep/del117. Epub 2006 Jul 20. PubMed 16857887 ↗
Friedler S, Raziel A, Schachter M, Strassburger D, Bukovsky I, Ron-El R. Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration. Hum Reprod. 1999 Aug;14(8):1944-8. doi: 10.1093/humrep/14.8.1944. PubMed 10438404 ↗
Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grondahl ML, Westergaard L, Andersen CY. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005 May;20(5):1213-20. doi: 10.1093/humrep/deh765. Epub 2005 Mar 10. PubMed 15760966 ↗
Mitwally MF, Gotlieb L, Casper RF. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause. 2002 Jul-Aug;9(4):236-41. doi: 10.1097/00042192-200207000-00004. PubMed 12082359 ↗
Wyatt KM, Dimmock PW, Ismail KM, Jones PW, O'Brien PM. The effectiveness of GnRHa with and without 'add-back' therapy in treating premenstrual syndrome: a meta analysis. BJOG. 2004 Jun;111(6):585-93. doi: 10.1111/j.1471-0528.2004.00135.x. PubMed 15198787 ↗
Forbush KT, Wildes JE, Pollack LO, Dunbar D, Luo J, Patterson K, Petruzzi L, Pollpeter M, Miller H, Stone A, Bright A, Watson D. Development and validation of the Eating Pathology Symptoms Inventory (EPSI). Psychol Assess. 2013 Sep;25(3):859-78. doi: 10.1037/a0032639. Epub 2013 Jul 1. PubMed 23815116 ↗
Franken IH, Muris P, Georgieva I. Gray's model of personality and addiction. Addict Behav. 2006 Mar;31(3):399-403. doi: 10.1016/j.addbeh.2005.05.022. Epub 2005 Jun 16. PubMed 15964149 ↗
Harrison A, O'Brien N, Lopez C, Treasure J. Sensitivity to reward and punishment in eating disorders. Psychiatry Res. 2010 May 15;177(1-2):1-11. doi: 10.1016/j.psychres.2009.06.010. Epub 2010 Apr 9. PubMed 20381877 ↗
Knutson B, Westdorp A, Kaiser E, Hommer D. FMRI visualization of brain activity during a monetary incentive delay task. Neuroimage. 2000 Jul;12(1):20-7. doi: 10.1006/nimg.2000.0593. PubMed 10875899 ↗

Study documents

Protocol and statistical analysis plan · Nov 11, 2021
Informed consent form · Jul 13, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Deidentified individual data that supports the results will be shared beginning 18 to 24 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Supporting information: Statistical analysis plan, Analytic code

Time frame: Deidentified individual data that supports the results will be shared beginning 18 to 24 months following publication.

Access criteria: Approval from an IRB, IEC, or REB, as applicable and execution of a data use/sharing agreement with UNC.

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Feb 2020 to primary completion in Apr 2022, 25 months.

Results were first posted in Jul 2022, 3 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Jan 8, 2020
First posted: Jan 13, 2020
StartActual: Feb 24, 2020
Primary completionActual: Apr 4, 2022
CompletionActual: Apr 4, 2022
Results first posted: Jul 26, 2022
Last update: Jul 26, 2022

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jul 26, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04225221
Lead sponsor: University of North Carolina, Chapel Hill
Collaborators: National Institute of Mental Health (NIMH)
Responsible party: Sponsor
First posted: Jan 13, 2020
Start date: Feb 24, 2020
Primary completion: Apr 4, 2022
Completion: Apr 4, 2022
Results posted: Jul 26, 2022
Last update: Jul 26, 2022

Study contacts

Jessica Baker, PhD

principal investigator · University of North Carolina, Chapel Hill

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Estradiol · Progesterone · Leuprolide

Other studies in this condition

Bulimia Nervosa →

Other studies from this sponsor

University of North Carolina, Chapel Hill →

Start the discussion