一项随机、安慰剂对照、双掩蔽机制的经皮雌激素替代治疗低雌激素源性进食障碍临床试验的研究方案，探讨雌激素在认知灵活性和奖励加工中的作用

IF 2 3区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary clinical trials Pub Date : 2025-04-26 DOI:10.1016/j.cct.2025.107924

Lauren Breithaupt , Meghan Slattery , Meghan Lauze , Felicia Petterway , Lauren Lindman , Mia Cravitz , Sarah Naticchia , Siddarth Seenivasa , Macy Powers , Kristin N. Javaras , David J. Alperovitz , Judith Halperin , Esther Dechant , Jennifer J. Thomas , Elizabeth A. Lawson , Hang Lee , Diego A. Pizzagalli , Adrienne L. Romer , Poornima Kumar , Franziska Plessow , Kamryn T. Eddy

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引用次数: 0

摘要

限制性进食障碍（EDs）与认知不灵活、奖励反应降低和倾向于延迟奖励有关，这有助于疾病维持和不良预后。雌激素水平低在急症患者中很常见，并且与认知灵活性差和其他情况下的奖励处理有关。我们描述了一项随机对照双盲试验，短期（12周）经皮雌激素（100 μg 17-β）替代与安慰剂比较，以测试雌激素对ED和低雌激素（ED- le）女性ED的认知灵活性、奖励反应、延迟折扣和ED病理的影响。研究对象将包括N = 120名ED-LE女性患者（14-35岁），并在基线、8周和12周进行临床、神经心理学和神经评估。结果主要结果包括8周认知灵活性、奖励反应性和延迟折扣变化的组间差异，以及12周ED病理变化的组间差异。次要结果将包括认知灵活性和奖励相关功能磁共振成像范式中8周神经激活变化的组间差异，以及8周认知灵活性、奖励反应性和延迟折扣变化对12周ED病理变化的中介作用。结论我们假设雌激素替代将(1)增加认知灵活性，奖励反应和延迟折扣，(2)减少ED病理；(3)认知灵活性、奖励反应性和延迟折扣的8周变化将介导ED病理的12周变化。这些数据将系统地探讨雌激素在与不良ED结果相关的关键神经认知特征中的作用，以指导针对这一人群的新干预措施的开发。

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Study protocol for a randomized, placebo-controlled, double-masked mechanistic clinical trial of transdermal estrogen replacement in hypoestrogenic eating disorders to explore the role of estrogen on cognitive flexibility and reward processing

Background

Restrictive eating disorders (EDs) are associated with cognitive inflexibility, reduced reward responsiveness, and tendency to favor delayed rewards, which contribute to illness maintenance and poor outcomes. Low estrogen is common in EDs and has been linked to poor cognitive flexibility and reward processing in other conditions. We describe a randomized controlled double-masked trial of short-term (12 weeks) transdermal estrogen (100 μg 17-β) replacement versus placebo to test estrogen-effects on cognitive flexibility, reward responsiveness, delay discounting, and ED pathology in females with EDs and low estrogen (ED-LE).

Methods

Participants will include N = 120 females with ED-LE (14–35 years) with clinical, neuropsychological, and neural assessments occurring at baseline, eight weeks, and 12 weeks.

Results

Primary outcomes will include between-group differences in 8-week change in cognitive flexibility, reward responsiveness, and delay discounting, and between-group differences in 12-week change in ED pathology. Secondary outcomes will include between-group differences in 8-week change in neural activation during cognitive flexibility and reward-related functional magnetic resonance imaging paradigms and mediation effects of 8-week change in cognitive flexibility, reward responsiveness, and delay discounting on 12-week change in ED pathology.

Conclusion

We hypothesize that estrogen replacement will (1) increase cognitive flexibility, reward responsiveness, and delay discounting, and (2) reduce ED pathology; and (3) 8-week changes in cognitive flexibility, reward responsiveness, and delay discounting will mediate 12-week changes in ED pathology. These data will systematically probe the role of estrogen in key neurocognitive features associated with poor ED outcomes to guide development of novel interventions for this population.

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来源期刊

Contemporary clinical trials 医学-药学

CiteScore

3.70

自引率

4.50%

发文量

281

审稿时长

44 days

期刊介绍： Contemporary Clinical Trials is an international peer reviewed journal that publishes manuscripts pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from disciplines including medicine, biostatistics, epidemiology, computer science, management science, behavioural science, pharmaceutical science, and bioethics. Full-length papers and short communications not exceeding 1,500 words, as well as systemic reviews of clinical trials and methodologies will be published. Perspectives/commentaries on current issues and the impact of clinical trials on the practice of medicine and health policy are also welcome.