CLONIDINE IN ADHD

可乐定治疗多动症

• 批准号: 6394211
• 负责人: FLOYD R SALLEE
• 金额: $ 72.51万
• 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/6394211
• 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）是一种常见的精神健康障碍，发病率很高，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疗法或联合疗法。 缺乏足够的ADHD疗效和安全性数据，并且CLON未被FDA批准用于ADHD。与哌醋甲酯（MPH）组合的优点在于，它可以是协同的，可以延长兴奋剂作用，和/或CLON可以解决某些单独用兴奋剂不能治疗的核心症状。 没有数据支持这些理由，尽管有与联合治疗相关的严重不良事件的报告，但联合治疗的处方越来越多。CLON尚未在原发性ADHD中进行全面研究，但NINDS赞助的对CLON单独使用和与MPH联合使用的安全性和有效性的评估目前正在Tourette综合征伴ADHD（TACT）儿童中进行。 然而，TACT受试者可能主要是“注意力不集中”亚型，与最常见于原发性ADHD的混合型相反。 TACT数据也不能外推至原发性ADHD，因为TACT中的CLON治疗具有治疗抽搐和ADHD的双重目标，因此给药间隔和潜在的安全性结果（如果不良事件与剂量相关）可能不容易应用于原发性ADHD。 因此，TACT的有效性和安全性数据可能不足以用于主要ADHD治疗，而大多数CLON都是用于主要ADHD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现有基础设施降低了成本; 2）有机会在研究中汇集安全性数据，使得可以检测到低频率的不良事件; 3）比较原发性ADHD与ADHD伴多发性抽动秽语综合征的治疗结果，以确定CLON是否在“注意力不集中亚型”与“多动/冲动”或组合亚型中具有不同的作用;以及4）确定MPH的长期治疗是否有助于抽动障碍的发展。我们提出了一个多中心，对照研究的克隆，MPH，克隆加MPH与原发性多动症的儿童。 本研究将A）确定CLON治疗儿童ADHD的安全性和有效性; B）评价与标准MPH治疗相比，CLON+MPH联合治疗ADHD的安全性和有效性; C）为所有受试者提供一个在研究过程中随访抽搐发展的lyr扩展。