CLONIDINE IN ADHD

可乐定治疗多动症

• 批准号: 6805164
• 负责人: FLOYD R SALLEE
• 金额: $ 59.85万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-18 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6805164
• 关键词: Tourette' s syndrome; adolescence (12-20); attention deficit disorder; child (0-11); clinical research; clinical trials; clonidine; combination chemotherapy; comorbidity; human subject; human therapy evaluation; mental disorder chemotherapy; methylphenidate; pediatric pharmacology

Attention Deficit, Hyperactivity disorder (ADHD) is a common mental health disorder of significant morbidity for which approximately 100,000 children yearly are treated with clonidine (CLON) in the US, either as an alternative to psychostimulants, or as combination therapy. Adequate ADHD efficacy and safety data are lacking and CLON is not FDA approved for ADHD. Rationales for combination with methylphenidate (MPH) are that it may be synergistic, may extend the stimulant effect, and/or that CLON may address certain core symptoms not treated by stimulants alone. No data support these rationales, yet the combination is increasingly being prescribed despite reports of serious adverse events linked to combination therapy. CLON has yet to be comprehensively studied in primary ADHD, but an NINDS sponsored evaluation of the safety and efficacy of CLON alone and in combination with MPH is currently being conducted in children with Tourette Syndrome with comorbid ADHD (TACT). TACT subjects however may be predominantly "inattentive" subtype, in contrast to combined type, most commonly seen in primary ADHD. TACT data also cannot be extrapolated to primary ADHD because treatment with CLON in TACT is dually targeted to the treatment of both tics and ADHD such that dosing interval and potentially safety findings (if adverse events are dose related) may not be readily applied to primary ADHD. Efficacy and safety data from TACT therefore may be inadequate for primary ADHD treatment, for which the majority of CLON is prescribed. The clinical trial machinery and expertise of the TACT team however is uniquely positioned to study CLON in primary ADHD. Advantages would be: 1) reduced cost by using TACT existing infrastructure; 2) an opportunity to pool safety data across studies such that low frequency adverse events may be detected; 3) to compare therapeutic outcomes in primary ADHD to ADHD with comorbid Tourette Syndrome to determine if CLON has differential effects in "inattentive subtype" versus "hyperactive/impulsive" or combined subtypes; and 4) to determine if chronic treatment with MPH can contribute to the development of tic disorder. We propose a multicenter, controlled study of CLON, MPH, and CLON plus MPH for children with primary ADHD. The study will A) determine the safety and efficacy of CLON for the treatment of ADHD in children; B) evaluate the safety and efficacy of combined CLON+MPH for treatment of ADHD compared to standard MPH therapy; C) provide a lyr extension for all subjects to follow-up tic development during course of the study.

注意力不足，多动症（ADHD）是一种普遍的心理健康障碍，具有严重的发病率，每年约有100,000名儿童在美国接受可乐定（克隆）治疗，既可以替代精神刺激剂，也可以作为组合治疗。 缺乏足够的多动症和安全性数据，并且克隆未获得ADHD的FDA批准。与哌醋甲酯（MPH）结合的理由是，它可能是协同作用，可以扩展刺激效应，并且/或克隆可能会解决单独刺激物不治疗的某些核心症状。 没有数据支持这些理由，但是尽管有与联合疗法有关的严重不良事件的报道，但这种组合越来越多。克隆尚未在初级多动症中进行全面研究，但是NINDS赞助了单独使用克隆的安全性和有效性的评估，并且目前正在与Comorbid ADHD（CAT）的儿童进行Tourette综合征（TAC）的儿童进行MPH的结合。 然而，与组合类型相比，TACT受试者可能主要是“注意力不集中”的亚型。 TACT数据也不能推断到主要的ADHD，因为用TACT的CLON处理双重治疗是针对TICS和ADHD的治疗，因此剂量间隔和潜在的安全性发现（如果与不良事件相关）不容易将其应用于初级ADHD。 因此，来自TAC的功效和安全性数据可能不足以进行初级多动症治疗，为此开处方了大多数克隆。 然而，TACT团队的临床试验机制和专业知识是在主要多动症中研究克隆的独特位置。 优势将是：1）使用现有的基础设施降低成本； 2）有机会跨研究汇总安全数据，以便可以检测到低频不良事件； 3）将初级多动症的治疗结果与ADHD与合并症综合综合征进行比较，以确定克隆在“不专心的亚型”与“多动/冲动/冲动”或组合亚型中是否具有差异效应； 4）确定使用MPH的慢性治疗是否可以导致TIC疾病的发展。我们建议针对主要多动症儿童的克隆，MPH和克隆和MPH的多中心，对照研究。 该研究将a）确定克隆在儿童治疗多动症的安全性和功效； b）与标准MPH疗法相比，评估CLON+MPH联合+MPH联合治疗ADHD的安全性和功效； c）在研究过程中，为所有受试者提供了ly范围的延伸。