Cytogenetic damage in ADHD children treated with methylphenidate or Adderall

使用哌醋甲酯或阿得拉治疗的多动症儿童的细胞遗传学损伤

• 批准号: 7734555
• 负责人: kristine l witt
• 金额: $ 7.44万
• 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/7734555
• 关键词: Academic Medical Centers; Academy; Adderall; Adolescent Psychiatry; Age; American; Amphetamines; Attention; Attention deficit hyperactivity disorder; Child; Childhood; Chromosome abnormality; Condition; Consent; Cytogenetics; Data; Data Collection; Diagnosis; Diagnostic; Disease; Dose; Drug Prescriptions; End Point; Enrollment; Ethnic Origin; Exclusion; Exposure to; Goals; Human; Investigation; Journals; Laboratories; Laboratory Procedures; Legal Guardians; Lymphocyte; Manuscripts; Measurement; Measures; Methylphenidate; Monitor; Numbers; Paper; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Physicians; Pilot Projects; Practice Guidelines; Protocols documentation; Publications; Publishing; Race; Reporting; Salts; Sampling; Schedule; Scientist; Sister Chromatid Exchange; Study Subject; Voice; Writing; base; clinically relevant; comparative; design; disorder subtype; micronucleus; programs; psychologic; sex

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 DeficitHyperactivity 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 employed a more extensive protocol and carefully monitored data collection. Recruitment and enrollment of study subjects occurred through the Duke University Medical Center ADHD Program. In this study, we investigated 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 were followed, and all laboratory procedures were conducted under Good Laboratory Practice guidelines. We used 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 was 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. Our goal was to enroll 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 was indicated. Half the children began treatment with methylphenidate-based therapy and half the children began treatment with Adderall. Assignment to study group was random because the two drug therapies are considered to be interchangeable. No exclusions by ADHD subtype were necessary because there is no correlation between treatment, dose, and ADHD subtype. This number of subjects (60) was selected to give us sufficient power to detect treatment-related cytogenetic changes or support negative observations. Study subjects were eligible for enrollment if they had no co-morbid psychological conditions, no physical conditions that contraindicated stimulant treatment, were ADHD-drug naive, and had not received diagnostic x-rays in the past 3 months. All study subjects or their legal guardians provided informed written consent. As of August 120, 2008, this study is complete. The data have been analyzed and the manuscript reporting the results has been accepted for publication in the Journal of the American Academy of Child and Adolescent Psychiatry. Results will be publicly available when the manuscript is published.

该研究旨在阐明来自早期试点研究的结果，该研究报告了在用基于苯甲酸甲酯的药物治疗3个月后，12名被诊断患有注意力缺陷多动障碍（ADHD）的儿童（6-12岁）的淋巴细胞中染色体损伤的三种测量值显著增加（El-Zein等人，2005年）。本研究中的重大方案缺陷引起了对结论的关注（普雷斯顿等人，2005），并促使设计了这项重复研究，采用了更广泛的协议，并仔细监测数据收集。研究受试者的招募和入组通过杜克大学医学中心ADHD项目进行。 在本研究中，我们研究了与早期初步研究中分析的相同的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）。遵循普遍确立的淋巴细胞中这三个终点分析方案，所有实验室程序均按照药物非临床研究质量管理规范指南进行。 我们使用了相同的分析时间表：在开始药物治疗前测量每例受试者淋巴细胞样本中的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（一种苯丙胺盐的组合）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%，因此在本方案中增加了对Adderall治疗儿童淋巴细胞中细胞遗传学终点的研究，以向临床医生和患者提供比较数据。 目前尚无已发表的Adderall在人类中的细胞遗传学数据。Adderall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处方的因素。 我们的目标是入组60名儿童，年龄6-12岁（含），性别不限，种族不限，由杜克ADHD工作人员诊断为ADHD，任何亚型，适用兴奋剂药物治疗。 一半的儿童开始用哌甲酯治疗，一半的儿童开始用Adderall治疗。 随机分配至研究组，因为认为两种药物治疗可以互换。 不需要根据ADHD亚型排除，因为治疗、剂量和ADHD亚型之间没有相关性。选择这一数量的受试者（60例）是为了使我们有足够的把握度检测治疗相关的细胞遗传学变化或支持阴性观察结果。 如果研究受试者没有共病的心理状况，没有禁止兴奋剂治疗的身体状况，是ADHD药物初治，并且在过去3个月内没有接受过诊断X射线检查，则有资格入组研究。 所有研究受试者或其法律的监护人均提供了书面知情同意书。 截至2008年8月120日，本研究已完成。 这些数据已被分析，报告结果的手稿已被接受发表在美国儿童和青少年精神病学学会杂志上。 结果将在手稿出版时公开。

项目成果

Methylphenidate and chromosome damage.

哌甲酯和染色体损伤。

• DOI: 10.1016/j.canlet.2007.10.017
• 发表时间: 2008
• 期刊: Cancer letters
• 影响因子: 9.7
• 作者: Jacobson-Kram,David;Mattison,Donald;Shelby,Michael;Slikker,William;Tice,Raymond;Witt,Kristine
• 通讯作者: Witt,Kristine

Methylphenidate and amphetamine do not induce cytogenetic damage in lymphocytes of children with ADHD.

哌醋甲酯和安非他明不会引起多动症儿童淋巴细胞的细胞遗传学损伤。

• DOI: 10.1097/chi.0b013e3181893620
• 发表时间: 2008
• 期刊: Journal of the American Academy of Child and Adolescent Psychiatry
• 影响因子: 13.3
• 作者: Witt,KristineL;Shelby,MichaelD;Itchon-Ramos,Nilda;Faircloth,Melissa;Kissling,GraceE;Chrisman,AllanK;Ravi,Hima;Murli,Hemalatha;Mattison,DonaldR;Kollins,ScottH
• 通讯作者: Kollins,ScottH