CLONIDINE IN ADHD

可乐定治疗多动症

• 批准号: 6127590
• 负责人: FLOYD R SALLEE
• 金额: $ 85.02万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 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 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6127590
• 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.

注意力缺陷多动障碍 (ADHD) 是一种发病率很高的常见精神健康障碍，在美国每年约有 100,000 名儿童接受可乐定 (CLON) 治疗，作为精神兴奋剂的替代药物或联合治疗。 缺乏足够的 ADHD 疗效和安全性数据，并且 CLON 尚未获得 FDA 批准用于 ADHD。与哌醋甲酯 (MPH) 组合的理由是它可能具有协同作用，可能会延长兴奋剂效果，和/或 CLON 可能会解决某些单独使用兴奋剂无法治疗的核心症状。 没有数据支持这些理由，但尽管有报告称联合治疗存在严重不良事件，但越来越多的人开始使用联合治疗。 CLON 尚未在原发性 ADHD 中进行全面研究，但 NINDS 赞助的一项评估，针对 CLON 单独使用以及与 MPH 联合使用的安全性和有效性，目前正在患有多动症的抽动秽语综合征 (TACT) 儿童中进行。 然而，与最常见于原发性 ADHD 的组合型相比，TACT 受试者可能主要是“注意力不集中”亚型。 TACT 数据也不能外推至原发性 ADHD，因为 TACT 中的 CLON 治疗双重针对抽动症和 ADHD 的治疗，因此给药间隔和潜在安全性发现（如果不良事件与剂量相关）可能不易应用于原发性 ADHD。 因此，TACT 的疗效和安全性数据可能不足以用于 ADHD 的初级治疗，而大多数 CLON 都是用于这种治疗。 然而，TACT 团队的临床试验机制和专业知识在研究原发性 ADHD 中的 CLON 方面具有独特的优势。 优点是： 1) 通过使用 TACT 现有基础设施降低成本； 2）有机会汇集跨研究的安全数据，以便可以检测到低频不良事件； 3) 比较原发性 ADHD 与合并抽动秽语综合征的 ADHD 的治疗结果，以确定 CLON 在“注意力不集中亚型”与“多动/冲动”或组合亚型中是否具有不同作用； 4) 确定 MPH 的长期治疗是否会导致抽动障碍的发生。我们建议对患有原发性 ADHD 的儿童进行 CLON、MPH 和 CLON 加 MPH 的多中心对照研究。 该研究将 A) 确定 CLON 治疗儿童 ADHD 的安全性和有效性； B) 与标准 MPH 治疗相比，评估 CLON+MPH 联合治疗 ADHD 的安全性和有效性； C) 为所有受试者提供 lyr 扩展，以便在研究过程中跟踪抽动的发展。