The Role of Estrogen in the Neurobiology of Eating Disorders: A Study of Cognitive Flexibility and Reward in Eating Disorders
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Change in inhibition-switching performance on the Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWIT) with 17-β estradiol versus placebo
研究概览
简要总结
This is a randomized, double blind, placebo-controlled study of the effects of transdermal estradiol versus placebo on cognitive flexibility, reward processing, and eating disorder pathology in hypoestrogenemic female adolescents and young adults (ages 14-35 years) with an eating disorder characterized by extreme dietary restriction and/or excessive exercise. Subjects will be randomized 1:1 to 12 weeks of transdermal estradiol with cyclic progesterone or placebo patches and cyclic placebo pills. Study visits include a screening visit to determine eligibility and visits at baseline, 8 weeks, and 12 weeks. Study procedures comprise behavioral, neuroimaging, and endocrine assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 14 Years 至 35 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •14-35 years
- •Bone age ≥13.5 years (applicable only for participants <16 years)
- •Clinically significant eating disorder characterized by restriction and/or excessive exercise and high drive for thinness
- •Hypoestrogenemia: Oligo-amenorrhea defined as lack of menses for ≥3 months within a 6-month period of oligomenorrhea (cycle length ≥5 weeks) or absence of menses at >15 years if premenarchal or low estradiol levels evaluated by the study physician
- •Low or normal weight defined by a body mass index that is <85th percentile for 14-18 year olds and a body mass index <25 kg/m2 for adults
排除标准
- •Suicidal ideation where outpatient treatment is determined unsafe by study clinician
- •Other causes of oligo-amenorrhea, unless a study clinician determines that missed menstrual periods are more likely a consequence of restrictive eating
- •Medications that contain estrogen ± progesterone within the past 3 months
- •Levonorgestrel-releasing intrauterine device if subject is unable to provide two to three weekly blood samples for estradiol of if estradiol levels are determined to be too high by study doctor
- •Neurological or psychiatric disorders that may impact neural circuitry of interest
- •Lifetime history of seizure disorder or electroconvulsive therapy
- •Pregnancy/breastfeeding
- •Gastrointestinal tract surgery
- •Contraindications to estrogen use
- •Any other significant illness or condition that the investigator determines could interfere with study participation or safety or put the subject at any unnecessary risk
研究组 & 干预措施
Placebo
干预措施: Placebo patch and pill (Drug)
17-β estradiol with cyclic progesterone
干预措施: 17-β estradiol transdermal patches with cyclic progesterone (Drug)
结局指标
主要结局
Change in inhibition-switching performance on the Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWIT) with 17-β estradiol versus placebo
时间窗: Baseline to 8 weeks
Change in Temporal Experience of Pleasure Scale (TEPS) Consummatory Pleasure score (Range: 8-48; direction: Higher values indicate more pronounced consummatory pleasure/better outcome) with 17-β estradiol versus placebo
时间窗: Baseline to 8 weeks
Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo
时间窗: Baseline to 8 weeks
Change in Eating Disorder Inventory-3 (EDI-3) Body Dissatisfaction score (Range: 0-36; direction: Higher values indicate more pronounced body dissatisfaction/worse outcome) with 17-β estradiol versus placebo
时间窗: Baseline to 12 weeks
Change in EDI-3 Drive for Thinness score (Range: 0-28; direction: Higher values indicate more pronounced drive for thinness/worse outcome) with 17-β estradiol versus placebo
时间窗: Baseline to 12 weeks
次要结局
- Change in functional magnetic resonance imaging (fMRI) activation of the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) during a task switching paradigm with 17-β estradiol versus placebo(Baseline to 8 weeks)
- Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo(Baseline to 12 weeks)
- Change in the Eating Disorder Examination (EDE) Dietary Restraint subscale (Range: 0-6; direction: Higher values indicate more pronounced dietary restraint/worse outcome) with 17-β estradiol versus placebo(Baseline to 12 weeks)
- Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-β estradiol versus placebo(Baseline to 8 weeks)
- Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-β estradiol versus placebo(Baseline to 8 weeks)
研究者
Madhusmita Misra
Division Chief, Pediatric Endocrinology
Massachusetts General Hospital