Cytogenetic damage in ADHD children treated with methylp

使用甲基p治疗的多动症儿童的细胞遗传学损伤

• 批准号: 7330704
• 负责人: kristine l witt
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7330704
• 关键词: Cytogenetic; damage; ADHD; children; treated

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.

本研究旨在澄清早期试点研究的结果，该研究报告了 12 名被诊断患有注意力缺陷/多动障碍 (ADHD) 的儿童（6-12 岁）在接受基于哌醋甲酯的药物治疗 3 个月后，淋巴细胞的三项染色体损伤指标显着增加（El-Zein 等，2005）。这项研究中的重大方案缺陷引起了人们对结论的担忧（Preston 等，2005），并促使这项重复研究的设计采用了更广泛的方案并仔细监测数据收集。研究对象的招募和注册是通过杜克大学医学中心 ADHD 项目进行的。 在这项研究中，我们正在研究早期试点研究中分析的相同 3 种细胞遗传学损伤指标（微核、姐妹染色单体交换、染色体畸变）。遵循普遍建立的淋巴细胞这三个终点分析方案，所有实验室程序均按照良好实验室规范指南进行。我们使用相同的分析时间表：在开始药物治疗之前测量从每位受试者获得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。由于阿得拉（一种安非他明盐的组合）越来越多地用于治疗儿童 ADHD，目前约占 ADHD 患者所有新药处方的 50%，因此本方案中添加了对接受阿得拉治疗的儿童淋巴细胞的细胞遗传学终点的调查，以便为临床医生和患者提供比较数据。目前还没有公布阿得拉在人类中的细胞遗传学数据。阿得拉和哌醋甲酯被认为同样有效，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 名儿童，年龄 6-12 岁，不限性别，不限民族和种族，由杜克 ADHD 工作人员诊断为 ADHD 任何亚型，需要使用兴奋剂进行药物治疗，将纳入本研究。 30 名儿童将开始接受基于哌醋甲酯的治疗，30 名儿童将开始接受阿德拉治疗。研究组的分配是随机的，因为两种药物疗法被认为是可以互换的。考虑到人员流失，将超额招募约 20% 的受试者，并确保每个治疗组至少有 30 名受试者。无需按 ADHD 亚型进行排除，因为治疗、剂量和 ADHD 亚型之间不存在相关性。这个受试者数量 (60) 将为我们提供足够的能力来检测与治疗相关的细胞遗传学变化或支持阴性观察结果 如果研究对象没有共病心理状况、没有妨碍兴奋剂治疗的身体状况、未曾使用过 ADHD 药物、并且在过去 3 个月内未接受过诊断性 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名受试者书面同意参与该研究，其中24名受试者同意并随机分组。七名受试者未能通过多动症诊断筛查，一名家长在筛查完成后撤回同意。筛查失败被转介给适当的医疗/心理资源，以帮助管理促使他们最初联系杜克大学的情况。到目前为止，已有 11 名受试者完成了研究，其中 13 名受试者目前正在积极研究。目前已安排 5 个受试者进行筛查预约。本次学习课程的入学人数已达到目标。