Bulimia NervosaPhase 2NCT04225221
Neurobiology of Bulimia Nervosa
A Phase 2 study testing Estradiol, Micronized progesterone and Leuprolide Acetate in people with Bulimia Nervosa, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Bulimia Nervosa
- What is being tested?
- Estradiol, Micronized progesterone and Leuprolide Acetate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2020to 4 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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;
Show all 26Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: Ovarian Hormones, Reward Response, and Binge Eating in Bulimia Nervosa: An Experimental Design
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
- Bulimia Nervosa
- Being tested
- Estradiol, Micronized progesterone, Leuprolide Acetate, Placebo Oral Capsule
- Keywords
- bulimia nervosa, binge eating, eating disorder, estrogen
- Medical subject headings
- Bulimia Nervosa, Bulimia, Feeding and Eating Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Also called E2, Estrace
During estradiol administration, 2mg of estradiol is given twice daily via oral capsule.
Micronized progesteroneDrug
Also called P4, Prometrium
During progesterone administration, 200mg of progesterone is given twice daily via oral capsule.
Leuprolide AcetateDrug
Also called Lupron Depot
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 CapsuleDrug
Also called Sugar pill
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.
| Study group | Role | What they receive |
|---|---|---|
| Sequence A: estradiol followed by progesterone | Experimental | 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. Receives: Drug: Estradiol; Drug: Micronized progesterone; Drug: Leuprolide Acetate; Drug: Placebo Oral Capsule |
| Sequence B: progesterone followed by estradiol | Experimental | 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. Receives: Drug: Estradiol; Drug: Micronized progesterone; Drug: Leuprolide Acetate; Drug: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start24 Feb 2020
- Primary completion4 Apr 2022
- Study completion4 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Bulimia NervosaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Jessica Baker, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04225221
- Sponsor's protocol ID
- 19-2343
- Other IDs
- R21MH121726
- Status last verified
- Jun 2022
- First submitted
- 8 Jan 2020
- Last updated
- 26 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
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 23585773Edler 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 17038206Klump 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 18307829Lester 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 12537036Price 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 3438453Mac 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 28439806Barth 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 25750611Yoest 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 25540977Frank 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 25902917Richard 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 28214679Klump 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 29927265Schmidt 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 9435325Bloch 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 10831472Ben 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 23545794Lee 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
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovarian Hormones, Reward Response, and Binge Eating in Bulimia Nervosa: An Experimental Design
- ClinicalTrials.gov ID
- NCT04225221
- Acronym / sponsor ID
- 19-2343
- Conditions
- Bulimia Nervosa
- Keywords
- bulimia nervosa, binge eating, eating disorder, estrogen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- 4 Apr 2022 (actual)
- Study completion
- 4 Apr 2022 (actual)
- First posted
- 13 Jan 2020 (actual)
- Results
- Posted 26 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A: estradiol followed by progesterone | Experimental | Drug: Estradiol, Drug: Micronized progesterone, Drug: Leuprolide Acetate, Drug: Placebo Oral CapsuleParticipants 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. |
| Sequence B: progesterone followed by estradiol | Experimental | Drug: Estradiol, Drug: Micronized progesterone, Drug: Leuprolide Acetate, Drug: Placebo Oral CapsuleParticipants 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. |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (26 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EstradiolAlso: E2, EstraceDuring estradiol administration, 2mg of estradiol is given twice daily via oral capsule. | Drug | Sequence A: estradiol followed by progesterone, Sequence B: progesterone followed by estradiol |
| Micronized progesteroneAlso: P4, PrometriumDuring progesterone administration, 200mg of progesterone is given twice daily via oral capsule. | Drug | Sequence A: estradiol followed by progesterone, Sequence B: progesterone followed by estradiol |
| Leuprolide AcetateAlso: Lupron DepotInitial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months. | Drug | Sequence A: estradiol followed by progesterone, Sequence B: progesterone followed by estradiol |
| Placebo Oral CapsuleAlso: Sugar pillPlacebo 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. | Drug | Sequence A: estradiol followed by progesterone, Sequence B: progesterone followed by estradiol |
Primary outcome
Change in Binge Eating Sum Score
Time frame: 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 with binge eating behavior. Change is defined by an average change score.
Change in Weekly Average Binge-eating Frequency
Time frame: 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.
Change in Self-Reported Reward Sensitivity Subscale Score During Estradiol Manipulation
Time frame: 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.
Change in Response Latency to Reward During the Monetary Incentive Delay Task During Estradiol Manipulation
Time frame: 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.
Change in Delay Discounting Parameter k Using the Monetary Choice Questionnaire With Estradiol Manipulation
Time frame: 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.
Change in Self-Reported Behavioral Inhibition Score During Estradiol Manipulation
Time frame: 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
Change in Behavioral Activation Score During Estradiol Manipulation
Time frame: 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.
Change in Behavioral Activation Reward Responsiveness With Estradiol Manipulation
Time frame: 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.
Change in Behavioral Inhibition During Estradiol Administration as Assessed Through a Behavioral Task
Time frame: 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.
Correlation Between Change in Reward Response and Change in Binge Eating Before and During Estradiol Manipulation
Time frame: 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 between change scores.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23585773Baker 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.
- Background: PubMed 17038206Edler 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.
- Background: PubMed 18307829Klump 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.
- Background: PubMed 12537036Lester 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.
- Background: PubMed 3438453Price 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.
- Background: PubMed 28439806Mac 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.
- Background: PubMed 25750611Barth 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.
- Background: PubMed 25540977Yoest KE, Cummings JA, Becker JB. Estradiol, dopamine and motivation. Cent Nerv Syst Agents Med Chem. 2014;14(2):83-9. doi: 10.2174/1871524914666141226103135.
- Background: PubMed 25902917Frank GK. Advances from neuroimaging studies in eating disorders. CNS Spectr. 2015 Aug;20(4):391-400. doi: 10.1017/S1092852915000012. Epub 2015 Apr 23.
- Background: PubMed 28214679Richard 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.
- Background: PubMed 29927265Klump 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.
- Background: PubMed 9435325Schmidt 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.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jessica Baker, PhD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Estradiol, Micronized progesterone and Leuprolide Acetate in people with Bulimia Nervosa, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Binge Eating Sum Score (time frame: Baseline (Day 14 of baseline) to End of Intervention (Day 14 of each intervention)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04225221, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2022.