SMART Use of Medication for the Treatment ofAdolescent Severe Obesity

明智地使用药物治疗青少年严重肥胖

• 批准号: 10657656
• 负责人: Claudia K Fox
• 金额: $ 53.99万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10657656
• 关键词: Address; Adolescent; Adolescent obesity; Affect; Age; Biological; Body Weight decreased; Body mass index; Body measure procedure; Characteristics; Chronic; Clinical Trials; Combination Medication; Complex; Data; Desire for food; Development; Disease; Dropout; Eating Behavior; Energy Metabolism; Evidence based treatment; Experimental Designs; Exposure to; Frustration; Goals; Healthcare; Heterogeneity; Hormones; Individual; Intervention; Lead; Life Style Modification; Mediator; Medical; Methodology; Morbid Obesity; Neuropsychology; Outcome; Participant; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phentermine; Recommendation; Recording of previous events; Refractory Disease; Research Methodology; Rest; Risk; Safety; Sequential Multiple Assignment Randomized Trial; Time; adaptive intervention; adult obesity; clinically relevant; clinically significant; compare effectiveness; design; evidence base; experience; improved outcome; individualized medicine; outcome prediction; patient response; predicting response; primary outcome; profiles in patients; public health relevance; recruit; relative effectiveness; response; sex; topiramate; treatment guidelines

Nearly 1 out of every 10 adolescents in the U.S. suffers from severe obesity (age- and sex-specific body mass index (BMI) ≥1.2 times the 95th percentile or ≥35 kg/m2), a chronic and debilitating disease. Current treatment guidelines call for 3 to 6 months of lifestyle modification therapy (LSMT) followed by consideration of adjunct pharmacotherapy for patients failing to respond to LSMT alone. However, this arbitrary time recommendation to wait 3 to 6 months before initiating medication is not evidence based. Waiting 6 months before making a change may be too long for patients who are struggling to achieve BMI reduction. Yet, 3 months may not be long enough to assess patient responsiveness to LSMT and could therefor lead to over medication. Further, no guidance exists regarding how to manage patients who are non-responsive to first-line pharmacotherapy. For adults with obesity, treatment with pharmacotherapy routinely includes combination medications, such as phentermine+topiramate. Yet for adolescents with severe obesity, a group for whom limiting unnecessary medication exposure is highly valued, switching from one monotherapy to another with a different mechanism of action (e.g. switching from phentermine to topiramate) may be preferable to adding a second medication (e.g. phentermine+topiramate). This gap in evidence-based treatment guidelines that address the optimal timing and sequence of adjunct pharmacotherapy is difficult to fill because of the response heterogeneity to LSMT and pharmacotherapy; using a “one-size-fits-all” approach will fail to help the non-responders and may unnecessarily “over-treat” the responders. Instead, adaptive interventions have the potential to maximize outcomes for more patients while limiting risk from exposure to ineffective and/or needless medications. Specifically, adaptive interventions tailor therapy according to predictors of response and then adjust the therapy over time based on on-going performance. Thus, the overarching goal of this clinical trial is to garner data that will inform the development of an adaptive medical intervention for the treatment of severe adolescent obesity that includes empirically-derived decision rules that address when adjunct pharmacotherapy should be initiated, and if starting pharmacotherapy, what is the best sequence or course of therapy. This study will utilize a sequential multiple assignment randomized trial (SMART) methodology which was developed specifically for constructing adaptive interventions. One hundred fifty adolescents (age 12-18 years) with severe obesity will be recruited in this 2-staged SMART that will systematically examine: 1) the effect of a 3-month versus 6-month response assessment to LSMT before starting adjunct pharmacotherapy; and 2) for non-responders to initial adjunct phentermine, the relative effectiveness of adding topiramate to phentermine versus switching to topiramate monotherapy. All participants will receive 12 months of intervention and the primary outcome will be change in BMI at 12 months.

在美国，每10名青少年中就有近1人患有严重肥胖症（年龄和性别特异性体重 体重指数（BMI）≥1.2乘以第95百分位数或≥35 kg/m2），是一种慢性衰弱性疾病。当前治疗 指南要求进行3至6个月的生活方式改变治疗（LSMT），然后考虑辅助治疗 对单独LSMT无效的患者进行药物治疗。然而，这个武断的时间建议 等待3至6个月才开始用药是没有证据的。等了6个月才做一个 对于那些努力实现BMI降低的患者来说，改变可能太长了。然而，3个月可能不是 足够长的时间来评估患者对LSMT的反应，因此可能导致过度用药。此外，本发明还 没有关于如何管理对一线药物治疗无反应的患者的指导。 对于患有肥胖症的成年人，常规药物治疗包括联合用药，例如 芬特明+托吡酯。然而，对于患有严重肥胖症的青少年， 高度重视药物暴露，从一种单药治疗转换为另一种具有不同机制的单药治疗 作用（例如从芬特明转换为托吡酯）可能优于添加第二种药物 (e.g.芬特明+托吡酯）。循证治疗指南中的这一空白， 辅助药物治疗的时间和顺序很难填补，因为反应异质性， LSMT和药物治疗;使用“一刀切”的方法将无法帮助无应答者， 不必要地“过度治疗”反应者。相反，适应性干预措施有可能最大限度地 同时限制暴露于无效和/或不必要的药物的风险。 具体来说，适应性干预根据反应的预测因素调整治疗，然后调整治疗方案。 治疗随着时间的推移基于正在进行的性能。因此，本临床试验的总体目标是 收集数据，为制定适应性医疗干预措施提供信息， 严重的青少年肥胖症，包括辅助性的决策规则， 应开始药物治疗，如果开始药物治疗，最佳顺序或 治疗过程。本研究将采用序贯多分配随机试验（SMART） 该方法是专门为构建适应性干预措施而开发的。一百五十 将招募患有严重肥胖症的青少年（年龄12-18岁）参加该2阶段SMART， 系统地检查：1）3个月与6个月对LSMT的反应评估的影响， 开始辅助药物治疗;和2）对于初始辅助芬特明的无应答者， 在芬特明基础上加用托吡酯与改用托吡酯单药治疗的有效性比较。所有 参与者将接受12个月的干预，主要结局将是12个月时BMI的变化。 个月

项目成果

SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol.

明智地使用药物治疗青少年严重肥胖：一项序贯多重分配随机试验方案。

• DOI: 10.1016/j.cct.2024.107444
• 发表时间: 2024
• 期刊: Contemporary clinical trials
• 影响因子: 2.2
• 作者: Fox,ClaudiaK;Vock,DavidM;Sherwood,NancyE;Gross,AmyC;Ryder,JustinR;Bensignor,MeganO;Bomberg,EricM;Sunni,Muna;Bramante,CarolynT;Jacobs,Nina;Raatz,SarahJ;Kelly,AaronS
• 通讯作者: Kelly,AaronS