Development of a Pharmacodynamic Biomarker of Opioid Antagonism in Adolescents with Eating Disorders

青少年饮食失调阿片类药物拮抗药效生物标志物的开发

• 批准号: 10662801
• 负责人: Stephani L Stancil
• 金额: $ 18.75万
• 依托单位: CHILDREN'S MERCY HOSP (KANSAS CITY, MO)
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662801
• 关键词: Active Learning; Address; Adolescence; Adolescent; Adult; Affect; Anorexia Nervosa; Anterior; Award; Binge Eating; Binge eating disorder; Biological Markers; Brain; Bulimia; Cardiac; Central Nervous System Agents; Child; Childhood; Clinical; Clinical Pharmacology; Clinical Sciences; Clinical Trials; Cross-Over Studies; Cross-Over Trials; Data; Development; Development Plans; Dorsal; Dose; Drug Design; Drug Exposure; Drug Kinetics; Eating Behavior; Eating Disorders; Environment; Enzymes; Food; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genetic Variation; Goals; Hour; Individual; Intervention; Joints; K-Series Research Career Programs; Link; Malnutrition; Medical center; Mental Health; Mental disorders; Mentors; Modeling; Morbidity - disease rate; Naltrexone; National Institute of Mental Health; Neuropharmacology; Obesity; Opioid; Opioid Antagonist; Opioid Receptor; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacotherapy; Placebo Control; Plasma; Play; Positioning Attribute; Precision therapeutics; Randomized; Randomized, Controlled Trials; Recommendation; Research Institute; Research Personnel; Rewards; Risk; Role; Sampling; Site; Structure; Substance Use Disorder; System; Taste Perception; Teenagers; Therapeutic; Training; Translational Research; Visualization; Vomiting; Vulnerable Populations; aged; alternative treatment; antagonist; binge type behavior; biomarker development; biomarker validation; brain reward regions; career; career development; cingulate cortex; craving; design; drug action; drug development; drug discovery; drug repurposing; efficacy trial; frontier; imaging facilities; interest; male; medical schools; model development; mortality; neuroimaging; neuroimaging marker; neuropsychopharmacology; pediatric department; pharmacodynamic biomarker; pharmacologic; pleasure; practical application; psychopharmacologic; purge; purging behavior; randomized, clinical trials; research and development; response; response biomarker; skill acquisition; substance use; translational scientist; Active Learning; Address; Adolescence; Adolescent; Adult; Affect; Anorexia Nervosa; Anterior; Award; Binge Eating; Binge eating disorder; Biological Markers; Brain; Bulimia; Cardiac; Central Nervous System Agents; Child; Childhood; Clinical; Clinical Pharmacology; Clinical Sciences; Clinical Trials; Cross-Over Studies; Cross-Over Trials; Data; Development; Development Plans; Dorsal; Dose; Drug Design; Drug Exposure; Drug Kinetics; Eating Behavior; Eating Disorders; Environment; Enzymes; Food; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genetic Variation; Goals; Hour; Individual; Intervention; Joints; K-Series Research Career Programs; Link; Malnutrition; Medical center; Mental Health; Mental disorders; Mentors; Modeling; Morbidity - disease rate; Naltrexone; National Institute of Mental Health; Neuropharmacology; Obesity; Opioid; Opioid Antagonist; Opioid Receptor; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacotherapy; Placebo Control; Plasma; Play; Positioning Attribute; Precision therapeutics; Randomized; Randomized, Controlled Trials; Recommendation; Research Institute; Research Personnel; Rewards; Risk; Role; Sampling; Site; Structure; Substance Use Disorder; System; Taste Perception; Teenagers; Therapeutic; Training; Translational Research; Visualization; Vomiting; Vulnerable Populations; aged; alternative treatment; antagonist; binge type behavior; biomarker development; biomarker validation; brain reward regions; career; career development; cingulate cortex; craving; design; drug action; drug development; drug discovery; drug repurposing; efficacy trial; frontier; imaging facilities; interest; male; medical schools; model development; mortality; neuroimaging; neuroimaging marker; neuropsychopharmacology; pediatric department; pharmacodynamic biomarker; pharmacologic; pleasure; practical application; psychopharmacologic; purge; purging behavior; randomized, clinical trials; research and development; response; response biomarker; skill acquisition; substance use; translational scientist

Project Summary The overall goal of this 4-year K23 proposal is to support Dr. Stephani Stancil to become an independent investigator in the field of pharmacodynamic biomarker development to support quantitative early-stage drug development in pediatric neuropsychopharmacology, specifically eating disorder therapeutics. This proposal aligns with NIMH’s prioritization of and the National Advisory Mental Health Council workgroup recommendations for quantitative pharmacologic early-stage trials, particularly in vulnerable populations. Eating disorders (ED), including Bulimia Nervosa, Anorexia Nervosa-Binge/Purge and Binge Eating Disorder, are characterized by binge eating and purge behaviors (e.g., vomiting), typically begin in adolescence, and affect up to 5% of teens. EDs are associated with significant morbidity (e.g., malnutrition, cardiac compromise, development of substance use disorder), have the highest mortality rate of any psychiatric illness and are not responsive to current pharmacotherapy. This career development proposal will leverage Dr. Stancil’s clinical pharmacology expertise in drug exposure inquiry and expand her career focus to clinical neuropsychopharmacology to enable her to define central nervous system drug action in children and adolescents. The comprehensive career development plan (CDP) contains three training objectives: 1) neuroimaging, 2) pediatric randomized clinical trials, and 3) exposure-response modeling, to transition Dr. Stancil into a successful, independent investigator. The CDP’s structured mentoring, didactic training and experiential learning will be applied to a randomized, placebo-controlled crossover trial in adolescents with Binge/Purge ED to accomplish the following aims: Aim 1) Determine the sensitivity of a neuroimaging biomarker to reward system modulation by opioid antagonism, Aim 2) Develop an Exposure-Response Model for naltrexone. Dr. Stancil’s career development and research will take place in a highly favorable and well- suited environment that includes a tertiary academic children’s medical center, children’s research institute, joint department of pediatrics shared by two regional medical schools, an outstanding imaging center and the Frontiers CTSA. After completing this project, Dr, Stancil will have advanced the field of pharmacodynamic biomarker development in pediatric mental health and generated data to support an R01 application to establish the validity of the proposed pharmacodynamic biomarker. She will be well-positioned to become a leader in the field of pharmacodynamic biomarker development and exposure-response linkage to de-risk early-stage drug development and facilitate a precision therapeutics approach to pediatric neuropsychopharmacology.

项目摘要 这项为期4年的K23提案的总体目标是支持Stephani Stancil博士成为独立 药效生物标志物开发领域的研究者，以支持定量早期药物 小儿神经心理药理学的发展，特别是饮食障碍疗法。这个建议 与NIMH的优先级和国家咨询心理健康委员会工作组保持一致 定量药学早期试验的建议，特别是在弱势群体中。 饮食失调（ED），包括神经性贪食症，神经性厌食症/清除和暴饮暴食障碍， 以暴饮暴食和清除行为（例如呕吐）的特征，通常在青少年开始，而 影响多达5％的青少年。 EDS与明显的发病率有关（例如，营养不良，心脏妥协， 药物使用障碍的发展），在任何精神病中的死亡率最高，并且不是 对当前药物治疗的反应。该职业发展建议将利用Stancil博士的临床 药物曝光询问方面的药理学专业知识，并将其职业重点扩展到临床 神经心理药理学使她能够定义儿童中枢神经系统药物作用， 青少年。综合职业发展计划（CDP）包含三个培训目标：1） 神经影像学，2）小儿随机临床试验和3）暴露反应建模，以过渡博士 Stancil成为一个成功的独立研究者。 CDP的结构化心理，教学培训和 经验学习将应用于青少年的随机，安慰剂对照的跨界试验 狂欢/清除以完成以下目的：目标1）确定神经影像的灵敏度 生物标志物通过阿片类拮抗作用奖励系统调制，目标2）开发暴露响应模型 Stancil博士的职业发展和研究将在高度良好且良好的 适合环境，包括三级学术儿童医学中心，儿童研究所， 两所地区医学院共享的儿科联合部，一个杰出的成像中心和 边境CTSA。完成该项目后，Stancil博士将推进药效学领域 小儿心理健康中的生物标志物开发并生成数据以支持R01应用 建立拟议的药效生物标志物的有效性。她会很适合成为一个 药效生物标志物开发和暴露响应连接到脱发风险的领导者 早期药物开发并促进小儿的精确疗法 神经心理药理学。