Cytogenetic damage in ADHD children treated with methylp

这项研究的目的是澄清早期一项初步研究的结果，该研究报告了12名被诊断为注意力缺陷/多动障碍(ADHD)的儿童(6-12岁)在接受以哌醋甲酯为基础的药物治疗3个月后，淋巴细胞染色体损伤的三项指标显著增加(El-Zein等人，2005年)。这项研究中显著的方案缺陷引起了人们对结论的担忧(Preston等人，2005年)，并促使设计了这项重复研究，采用了更广泛的方案和仔细监测的数据收集。研究对象的招募和注册是通过杜克大学医学中心ADHD计划进行的。 在这项研究中，我们正在研究早期初步研究中分析的相同的三种细胞遗传学损伤指标(微核、姐妹染色单体交换、染色体异常)。对淋巴细胞中这三个终点的分析遵循普遍建立的方案，所有实验室程序都在良好的实验室实践指南下进行。我们使用相同的分析程序：在药物治疗开始前测量每个受试者的淋巴细胞样本中的3个细胞遗传学终点，然后在药物治疗3个月后再次测量。由于Adderall是苯丙胺盐的一种组合，越来越多地用于儿童ADHD的治疗，现在约占ADHD患者所有新药处方的50%，因此在该方案中增加了对服用Adderall的儿童淋巴细胞细胞遗传学终点的调查，以向临床医生和患者提供比较数据。目前还没有已发表的Adderall在人类中的细胞遗传学数据。阿得拉和哌醋甲酯被认为是同样有效的，医生的选择是决定为任何特定患者开出哪种处方的因素。 60名6-12岁(含6-12岁)的儿童，不分性别、种族和种族，被杜克大学的ADHD工作人员诊断为患有ADHD的任何亚型，其兴奋剂药物治疗的对象将纳入本研究。30名儿童将开始接受以哌醋甲酯为基础的治疗，30名儿童将开始使用Adderall治疗。分配给研究组是随机的，因为这两种药物疗法被认为是可以互换的。将进行大约20%的超额招聘，以考虑到自然减员并确保每个治疗部门至少有30名受试者。没有必要排除ADHD亚型，因为治疗、剂量和ADHD亚型之间没有相关性。这一数量的受试者(60名)将给予我们足够的力量来检测与治疗相关的细胞遗传学变化或支持负面观察 如果研究对象没有合并心理疾病，没有违禁兴奋剂治疗的身体状况，患有ADHD药物幼稚，并且在过去3个月内没有接受过诊断X光检查，则有资格参加研究。所有研究对象或其法定监护人将提供知情的书面同意。 截至2006年8月16日，32名受试者提供了参与研究的书面同意，24人同意并随机进行了研究。七名受试者未能通过ADHD的诊断筛查，一名父母在筛查完成后撤回了同意。筛查失败被转介到适当的医疗/心理资源，以帮助管理促使他们最初联系杜克的情况。到目前为止，11名受试者已经完成了这项研究，目前有13名受试者正在进行研究。目前安排了5名受试者的筛查预约。学习课程中这一时间点的注册人数已经达到了目标。

This study was designed to clarify results from an earlier pilot study that reported significant increases in three measures of chromosomal damage in lymphocytes of 12 children (ages 6-12) diagnosed with Attention Deficit/Hyperactivity Disorder (ADHD), following 3 months of treatment with methylphenidate-based medications (El-Zein et al., 2005). Significant protocol deficiencies in this study raised concerns about the conclusions (Preston et al., 2005) and prompted the design of this repeat study that employs a more extensive protocol and carefully monitored data collection. Recruitment and enrollment of study subjects is occurring through the Duke University Medical Center ADHD Program. In this study, we are investigating the same 3 measures of cytogenetic damage (micronuclei, sister chromatid exchanges, chromosomal aberrations) that were analyzed in the earlier pilot study. Universally established protocols for analysis of these three endpoints in lymphocytes are followed, and all laboratory procedures are conducted under Good Laboratory Practice guidelines. We are using the same schedule of analysis: measurement of the 3 cytogenetic endpoints in lymphocyte samples obtained from each subject prior to the initiation of drug treatment, and then again after 3 months of pharmacotherapy. Because Adderall, a combination of amphetamine salts, is increasingly used in the treatment of ADHD in children and now constitutes approximately 50% of all new drug prescriptions for ADHD patients, an investigation of cytogenetic endpoints in lymphocytes of Adderall-treated children has been added to this protocol to provide comparative data to clinicians and to patients. There are currently no published cytogenetic data for Adderall in humans. Adderall and methylphenidate are considered equally effective and physician choice is the factor determining which is prescribed for any particular patient. 60 children, age 6-12 years inclusive, of either sex, and of any ethnicity and race, diagnosed by Duke ADHD staff with ADHD, any subtype, for whom pharmacological treatment with stimulants is indicated will be enrolled in this study. 30 children will begin treatment with methylphenidate-based therapy and 30 children will begin treatment with Adderall. Assignment to study group is random because the two drug therapies are considered to be interchangeable. Over-recruitment of approximately 20% will take place to account for attrition and ensure a minimum of 30 subjects per treatment arm. No exclusions by ADHD subtype are necessary because there is no correlation between treatment, dose, and ADHD subtype. This number of subjects (60) will give us sufficient power to detect treatment-related cytogenetic changes or support negative observations Study subjects are eligible for enrollment if they have no co-morbid psychological conditions, have no physical conditions that contraindicate stimulant treatment, are ADHD-drug naive, and have not received diagnostic x-rays in the past 3 months. All study subjects or their legal guardians will provide informed written consent. As of August 16, 2006, 32 subjects provided written consent to participate in the study, and 24 were consented and randomized. Seven subjects failed the diagnostic screen for ADHD, and one parent withdrew consent after screening was completed. Screen failures were referred to appropriate medical/psychological resources to aid in the management of the conditions that prompted them to contact Duke initially. Thus far, 11 subjects have completed the study, and 13 are currently active. Screening appointments are scheduled for 5 subjects at this time. Enrollment figures for this time point in the study course have met the target.