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10万名儿童接受可乐定(CLON)治疗，作为精神刺激剂的替代药物，或作为联合治疗。缺乏足够的ADHD疗效和安全性数据，而且Clon没有被FDA批准用于ADHD。与哌醋甲酯(MPH)联合使用的理由是，它可能是协同作用的，可以延长刺激效应，和/或克隆可能解决某些核心症状，而不是单独使用兴奋剂治疗。没有数据支持这些理由，然而，尽管有报道称与联合治疗有关的严重不良事件，但联合疗法仍在越来越多地被开出处方。Clon尚未在原发ADHD中进行全面研究，但NINDS赞助的一项关于Clon单独以及与MPH联合使用的安全性和有效性的评估目前正在进行中，用于患有多动症(TACT)的抽动症儿童。然而，机智受试者可能主要是“注意力不集中”亚型，而不是最常见于原发ADHD的混合型。TACT数据也不能外推到原发ADHD，因为CLON in TACT的治疗同时针对抽搐和ADHD，因此剂量间隔和潜在的安全发现(如果不良事件与剂量相关)可能不容易应用于原发ADHD。因此，TACT的有效性和安全性数据可能不足以用于主要的ADHD治疗，因为大多数药物都是克隆药。然而，TACT团队的临床试验机制和专业知识在研究原发ADHD的克隆性疾病方面具有独特的地位。优势将是：1)通过使用TACT现有的基础设施降低成本；2)有机会汇集各种研究的安全数据，以便可以检测到低频率的不良事件；3)比较患有ADHD和Tourette综合征的原发ADHD的治疗结果，以确定Clon在“注意力不集中亚型”和“多动/冲动”亚型或合并亚型中是否有不同的疗效；以及4)确定长期使用公共卫生药物治疗是否会导致抽动障碍的发展。我们建议对原发ADHD儿童进行克隆性、mph和克隆性+mph的多中心对照研究。这项研究将A)确定CLON治疗儿童多动症的安全性和有效性；B)评估与标准MPH疗法相比，联合使用CLON+MPH治疗ADHD的安全性和有效性；C)为所有受试者在研究过程中跟踪抽动的发展提供LYR延长。