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NCT04225221

Neurobiology of Bulimia Nervosa

Completed Phase 2 Results posted Last updated 26 July 2022
What this trial tests

Phase 2 trial testing Estradiol in Bulimia Nervosa in 10 participants. Completed in 4 April 2022.

Timeline
24 February 2020
Primary endpoint
4 April 2022
4 April 2022

Quick facts

Lead sponsorUniversity of North Carolina, Chapel Hill
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingdouble
Primary purposebasic science
Enrollment10
Start date24 February 2020
Primary completion4 April 2022
Estimated completion4 April 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of North Carolina, Chapel Hill

Who can join

Adults 18 to 42, female only, with Bulimia Nervosa. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Binge Eating Sum Score Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention)

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 wi

GroupValue95% CI
Estradiol-0.60± 4.7
Progesterone0.89± 4.7
Change in Weekly Average Binge-eating Frequency Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention)

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.

GroupValue95% CI
Estradiol-0.48± 2.6
Progesterone1.1± 4.7
Change in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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.

GroupValue95% CI
Estradiol-0.80± 1.9
Change in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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.

GroupValue95% CI
Estradiol-9.0± 44.0
Change in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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.

GroupValue95% CI
Estradiol-0.0047± 0.011
Change in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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

GroupValue95% CI
Estradiol0.90± 1.8
Change in Behavioral Activation Score During Estradiol Manipulation Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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.

Fun Seeking
GroupValue95% CI
Estradiol-0.10± 0.88
Drive
GroupValue95% CI
Estradiol0± 1.4
Change in Behavioral Activation Reward Responsiveness With Estradiol Manipulation Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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.

GroupValue95% CI
Estradiol0.10± 1.2
Change in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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.

GroupValue95% CI
Estradiol-0.094± 0.33
Correlation Between Change in Reward Response and Change in Binge Eating Before and During Estradiol Manipulation Primary · Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)

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 betw

BAS Reward Responsiveness
GroupValue95% CI
Estradiol-0.146
Sensitivity to Reward
GroupValue95% CI
Estradiol-0.132

Adverse events — posted to ClinicalTrials.gov

Time frame: 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).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Estradiol
Serious: 0/10 (0%)
Deaths: 0/10
Progesterone
Serious: 0/9 (0%)
Deaths: 0/9
Lupron and Placebo
Serious: 0/10 (0%)
Deaths: 0/10
Other adverse events (19 terms — click to expand)

ReactionSystemEstradiolProgesteroneLupron and Placebo
Hot FlashesEndocrine disorders
SpottingReproductive system and breast disorders
HeadacheNervous system disorders
BloatingGastrointestinal disorders
Abdominal CrampsReproductive system and breast disorders
Breast TendernessReproductive system and breast disorders
DrowsinessGeneral disorders
Localized rash at injection siteSkin and subcutaneous tissue disorders
DiarrheaGastrointestinal disorders
Appetite increaseMetabolism and nutrition disorders
Joint discomfortMusculoskeletal and connective tissue disorders
Memory ImpairmentNervous system disorders
FatigueGeneral disorders
Decreased Energy LevelGeneral disorders
InsomniaGeneral disorders
LethargicPsychiatric disorders
Menstrual BleedingReproductive system and breast disorders
Feeling HotGeneral disorders
Temperature DysregulationGeneral disorders

Data from ClinicalTrials.gov NCT04225221 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Approved and Pipeline Pharmacological Interventions for Eating Disorders (2010-2025): 15 Years of Progress (or Lack Thereof).
    Hirsch D, Reed J, Naqvi A, Ngor A, et al · · 2026 · PMID 41313392 · DOI 10.1007/s40263-025-01248-7

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Other trials of Estradiol

Trials testing the same drug.

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