Acetyl-L-carnitine supplementation for co-occurring depression and alcohol use disorder in adolescents: A randomized placebo-controlled pilot study

乙酰左旋肉碱补充剂治疗青少年并发抑郁症和酒精使用障碍：一项随机安慰剂对照试点研究

• 批准号: 10415146
• 负责人: Noah Emery
• 金额: $ 18.94万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415146
• 关键词: Acute; Address; Adolescence; Adolescent; Adolescent Development; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohols; Anhedonia; Antidepressive Agents; Attenuated; Award; Childhood; Clinical Research; Clinical Trials; Cognitive Therapy; Collection; Controlled Clinical Trials; Coupled; Data; Depressed mood; Development; Dropout; Ecological momentary assessment; Enrollment; Environment; Excitatory Amino Acid Antagonists; Exhibits; FDA approved; Frequencies; Future; Goals; Gold; Heavy Drinking; High Prevalence; Human; Integrative Therapy; Intervention; Laboratories; Levocarnitine Acetyl; Life; Literature; Longevity; Measures; Mental Depression; Mental disorders; Meta-Analysis; Method Acceptability; Methods; Motivation; N-Methylaspartate; Outcome; Participant; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Pilot Projects; Placebo Control; Placebos; Population; Property; Protocols documentation; Psychotherapy; Randomized; Relapse; Research; Rewards; Risk; Safety; Severities; Symptoms; Teenagers; Testing; Time; Treatment outcome; Treatment/Psychosocial Effects; United States National Institutes of Health; Withdrawal; Youth; adolescent alcohol treatment; adolescents with alcohol use disorders; age group; alcohol abuse therapy; alcohol comorbidity; alcohol craving; alcohol cue; alcohol effect; alcohol risk; alcohol use disorder; carnitine supplementation; comorbid depression; comorbidity; craving; critical period; cue reactivity; depressive symptoms; design; dietary supplements; drinking; effective intervention; endophenotype; high risk; improved; in vivo; medication compliance; novel; personalized medicine; primary endpoint; psychosocial; randomized placebo controlled trial; research and development; response; satisfaction; side effect; substance use

PROJECT SUMMARY/ABSTRACT Adolescence is a time of increased risk for alcohol use and depression. The co-occurrence of depression and alcohol use disorder (AUD) is one of the most prevalent and disabling psychiatric combinations in youth. The high prevalence makes this comorbidity a treatment norm and adolescents who struggle with this comorbidity exhibit poor treatment outcomes. As such, this population has considerable needs that are currently unmet by available treatments. One potential way to improve alcohol treatment for adolescents who have co-occurring depression is to augment the best available psychosocial interventions with pharmacotherapy designed to simultaneously treat both conditions. Currently there are four FDA approved medications for the treatment of AUD in adults. However, no medication is indicated for AUD in adolescents and controlled clinical trials with teenagers are noticeably absent for the literature. Improving treatment options for youth will require closing this important gap in medication development research. This two-year preparatory project (R21) will support the collection of pilot data for an integrative therapy that combines a promising novel medication, shown to reduce depressive symptoms, namely anhedonia, and alcohol craving in adults, with a gold standard psychosocial intervention for treating AUD among adolescents. Specifically, we will use rigorous protocol that embeds human lab and ecological momentary methods in the context of randomized placebo-controlled trial to examine if our candidate pharmacotherapy, acetyl-L-carnitine, enhances the effects of psychosocial treatment for AUD in adolescents with comorbid depression. Our specific aims are to: a) evaluate the feasibility, acceptability, and tolerability of acetyl-L-carnitine in adolescents with comorbid depression and AUD; b) test whether acetyl-L- carnitine decreases alcohol craving in the human laboratory and real-world setting and blunts the reinforcing effects of alcohol while drinking in daily life; c) test whether acetyl-L-carnitine reduces depressed mood, depression symptoms, and anhedonia; and d) test whether acetyl-L-carnitine decreases alcohol use in this population. Our aims address national priorities to gather safety and efficacy data on medications for treating AUD in youth. Findings from this exploratory study will contribute to personalized medicine for AUD by establishing evidence for targeting endophenotypes endemic to co-occurring depression and AUD. The proposed R21 will also provide critical pilot data for a future large-scale clinical trial of acetyl-L-carnitine in this population. This award is consistent with NIH's goal to address the nation's clinical research needs.

项目总结/摘要 青春期是酗酒和抑郁风险增加的时期。抑郁症的共同发生， 酒精使用障碍（AUD）是青年中最普遍和致残的精神病组合之一。的 高患病率使这种合并症成为一种治疗规范，患有这种合并症的青少年 治疗效果不佳。因此，这一人口有相当大的需求，目前没有得到满足， 可用的治疗。一种潜在的方法，以改善酒精治疗的青少年谁共同发生 抑郁症是为了加强最好的心理社会干预与药物治疗， 同时治疗这两种情况。目前有四种FDA批准的药物用于治疗 成人澳元然而，没有药物适用于青少年的AUD和对照临床试验， 青少年显然不喜欢文学作品。改善青年的治疗选择将需要关闭这一点， 药物开发研究的重要空白。这个为期两年的预备项目（R21）将支持 收集综合疗法的试点数据，该疗法结合了一种有前途的新型药物， 抑郁症状，即快感缺乏，以及成年人的酒精渴望， 治疗青少年AUD的干预措施。具体来说，我们将使用严格的协议， 在随机安慰剂对照试验的背景下， 如果我们的候选药物治疗，乙酰-L-肉毒碱，增强心理治疗的效果， 青少年共病抑郁症患者我们的具体目标是：a）评估可行性，可接受性， 乙酰-L-肉毒碱在患有抑郁症和AUD共病的青少年中的耐受性; B）测试乙酰-L-肉毒碱是否 肉毒碱在人类实验室和现实世界中降低了对酒精的渴望， 在日常生活中饮酒时酒精的影响; c）测试乙酰-L-肉碱是否降低抑郁情绪， 抑郁症状和快感缺乏;和d）测试乙酰-L-肉毒碱是否减少酒精的使用， 人口我们的目标是解决国家的优先事项，收集治疗药物的安全性和有效性数据， 年轻时的AUD这项探索性研究的结果将有助于通过以下方式为AUD提供个性化药物： 为靶向抑郁症和AUD共存的内源性表型提供证据。的 拟议的R21也将为未来的大规模临床试验提供关键的试点数据，乙酰-L-肉碱在这方面。 人口该奖项与NIH解决国家临床研究需求的目标一致。

项目成果

Trial-level bias score versus mean bias score: Comparison of the reliability and external validity using dot-probe task among daily smokers.

试验水平偏倚评分与平均偏倚评分：在日常吸烟者中使用点探针任务比较可靠性和外部效度。

• DOI: 10.1016/j.addbeh.2022.107456
• 发表时间: 2022
• 期刊: Addictive behaviors
• 影响因子: 4.4
• 作者: Yang,Min-Jeong;Borges,AllisonM;Emery,NoahN;Leyro,TeresaM
• 通讯作者: Leyro,TeresaM

Examining Associations Between Cannabis Use Disorder and Measures of Weekly and Within-Day Cannabis Frequency, Quantity, and Potency in College Students.

检查大学生大麻使用障碍与每周和当天大麻频率、数量和效力测量之间的关联。

• DOI: 10.1089/can.2022.0293
• 发表时间: 2023
• 期刊: Cannabis and cannabinoid research
• 影响因子: 3.8
• 作者: Piercey,CiannaJ;Mataczynski,Maggie;Stallsmith,VanessaT;Emery,NoahN;Karoly,HollisC
• 通讯作者: Karoly,HollisC

Focusing Narrowly on Model Fit in Factor Analysis Can Mask Construct Heterogeneity and Model Misspecification: Applied Demonstrations across Sample and Assessment Types.

狭隘地关注因子分析中的模型拟合可以掩盖构造异质性和模型错误指定：跨样本和评估类型的应用演示。

• DOI: 10.1080/00223891.2022.2047060
• 发表时间: 2023
• 期刊: Journal of personality assessment
• 影响因子: 3.4
• 作者: Stanton,Kasey;Watts,AshleyL;Levin-Aspenson,HollyF;Carpenter,RyanW;Emery,NoahN;Zimmerman,Mark
• 通讯作者: Zimmerman,Mark