A Novel Approach to Stimulant-Induced Weight Suppression and its Impact on Growth

一种抑制兴奋剂体重的新方法及其对生长的影响

基本信息

批准号：
8282802
负责人：
WILLIAM E PELHAM
金额：
$ 56.27万
依托单位：
FLORIDA INTERNATIONAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8282802
关键词：
Academy Acceleration Address Adherence Adolescence Adolescent Adolescent Psychiatry Adult Adverse effects Adverse event Age American Anorexia Appetite Depressants Attention deficit hyperactivity disorder Behavior Therapy Body Weight decreased Cells Child Child Psychiatry Childhood Chronic Clinical Treatment Combined Modality Therapy Control Groups DRD4 gene Data Deceleration Disease Dose Drug Industry Drug Prescriptions Early identification Early treatment Energy Intake Evaluation Evidence based treatment Failure Genetic Genotype Goals Growth Health Benefit Healthcare Height Holidays Home environment Hour Industry Intervention Investigation Late Effects Lead Mental disorders Methylphenidate Monitor Nursery Schools Parents Patients Pharmaceutical Preparations Pharmacological Treatment Positioning Attribute Preparation Preventive Intervention Public Health Randomized Randomized Controlled Trials Recovery Regimen Reporting Research Risk Risk Estimate Running Safety Schedule School-Age Population Schools Secondary to Seminal Site Supplementation Symptoms Techniques Therapeutic Effect Time Weight Work Youth active control arm combat common treatment control trial design dopamine transporter dosage drug efficacy energy balance experience falls functional disability innovation novel strategies prepuberty prevent public health relevance randomized trial response restoration social stigma standard of care success treatment adherence

Academy Acceleration Address Adherence Adolescence Adolescent Adolescent Psychiatry Adult Adverse effects Adverse event Age American Anorexia Appetite Depressants Attention deficit hyperactivity disorder Behavior Therapy Body Weight decreased Cells Child Child Psychiatry Childhood Chronic Clinical Treatment Combined Modality Therapy Control Groups DRD4 gene Data Deceleration Disease Dose Drug Industry Drug Prescriptions Early identification Early treatment Energy Intake Evaluation Evidence based treatment Failure Genetic Genotype Goals Growth Health Benefit Healthcare Height Holidays Home environment Hour Industry Intervention Investigation Late Effects Lead Mental disorders Methylphenidate Monitor Nursery Schools Parents Patients Pharmaceutical Preparations Pharmacological Treatment Positioning Attribute Preparation Preventive Intervention Public Health Randomized Randomized Controlled Trials Recovery Regimen Reporting Research Risk Risk Estimate Running Safety Schedule School-Age Population Schools Secondary to Seminal Site Supplementation Symptoms Techniques Therapeutic Effect Time Weight Work Youth active control arm combat common treatment control trial design dopamine transporter dosage drug efficacy energy balance experience falls functional disability innovation novel strategies prepuberty prevent public health relevance randomized trial response restoration social stigma standard of care success treatment adherence

展开

项目摘要

DESCRIPTION (provided by applicant): The most recent results from the MTA and PATS found that daily stimulant therapy with a 12 hour methylphenidate (MPH) regimen produced sustained growth deficits. In the MTA, there was as 1.7 inch difference in subjects medicated before and during the MTA vs. those never medicated. This difference persisted as long as medication was used, out to age 18. In PATS, one year of stimulant treatment at conservative doses produced a 20% reduction in expected height gain. This deceleration continued almost unabated over the next two years of medication use. Hence, there now appears to be evidence of concerning and persistent stimulant-induced growth suppression (SIGS). There were two major limitations of these findings. First, both used short acting stimulants, which are no longer the standard of care for pediatric ADHD. Extended release (ER) stimulants are the treatment of choice, but their longer therapeutic effects and ease of use may increase the chances of weight loss. Second was the failure to keep children in their assigned treatment cells past 14 months, thereby losing the effects of random assignment. In addition, anorexia and weight loss are two of the most commonly experienced adverse events with stimulants and are the side effects most likely to lead to treatment discontinuation. For a daily treatment, adherence is critical for success, and drug tolerability is a significant predictor of adherence. Even before PATS and the MTA, there was sizable stigma over the use of stimulants for ADHD, largely due to concerns about their long term safety in children. For these reasons, it is imperative to precisely estimate the risks of SIGS, examine the underlying mechanisms and develop treatments for it. While drug holidays and caloric supplementation are two common treatments for SIGS, there has been little systematic investigation of either. It is unknown if they are effective or feasible. Therefore, using a randomized adaptive design, we will evaluate the efficacy and feasibility of these two practices vs. routine monitoring of growth in 180 prepubertal children with ADHD. The study will address the limitations of prior work by using an ER MPH product and by keeping subjects in their assigned cells for 30 months. An additional 50 subjects will be treated solely with behavioral therapies to evaluate for growth abnormalities associated with ADHD. The study will assess will the risk of SIGS with ER stimulants and the underlying mechanisms while providing evidenced-based treatments for its management. Weight loss is a common side effect experienced by many of the millions of school-aged children prescribed stimulants that can lead to discontinuation of treatment. Now, there is evidence from PATS and the MTA that stimulants can lead to sustained and concerning growth suppression in children continuously treated with them throughout their childhood. This study holds substantial public health benefit as it will be the first randomized controlled trial for the treatment of stimulant induced growth suppression. In addition, it will enhance the understanding of growth abnormalities associated with ADHD vs. those secondary to persistent use of extended release stimulants as well as the mechanisms behind stimulant induced growth suppression.

描述（由申请人提供）：MTA和PATS的最新结果发现，使用12小时哌醋甲酯（MPH）方案的每日刺激治疗会产生持续的生长缺陷。在MTA中，在MTA之前和从未服药的受试者与从未服药的受试者相差1.7英寸。只要使用药物，这种差异就会持续到18岁。在PATS中，保守剂量的一年刺激治疗会使预期高度增长降低20％。在接下来的两年使用中，这种减速几乎没有减弱。因此，现在似乎有证据表明和持续的刺激性诱导的生长抑制（SIGS）。这些发现有两个主要局限性。首先，两者都使用短作用刺激剂，这不再是小儿多动症的护理标准。扩展释放（ER）兴奋剂是选择的治疗方法，但是它们的治疗效果较长和易于使用可能会增加体重减轻的机会。其次是在过去的14个月中未能将儿童留在分配的治疗细胞中，从而失去了随机分配的影响。此外，厌食症和体重减轻是最常见的带有兴奋剂的最常见的不良事件，并且是最有可能导致治疗中断的副作用。对于日常治疗，依从性对于成功至关重要，药物耐受性是依从性的重要预测指标。甚至在PATS和MTA之前，对于使用刺激剂的ADHD都有很大的污名，这在很大程度上是由于担心儿童长期安全。由于这些原因，必须精确估计SIG的风险，检查潜在的机制并为其开发治疗方法。尽管药物假期和热量补充是对SIG的两种常见治疗方法，但对任何一个系统的研究很少。未知它们是有效的还是可行的。因此，使用随机自适应设计，我们将评估这两种实践的疗效和可行性与180名ADHD前儿童的常规监测。该研究将通过使用ER MPH产品并将受试者保存在分配的细胞中30个月来解决先前工作的局限性。另外50名受试者将仅通过行为疗法进行治疗，以评估与多动症相关的生长异常。该研究将评估具有ER兴奋剂和潜在机制的SIG的风险，同时为其管理提供基于证据的治疗方法。体重减轻是数百万年龄的儿童开处方兴奋剂中的许多常见副作用，这些兴奋剂可能导致终止治疗。现在，有PATS和MTA的证据表明，兴奋剂可以导致持续和抑制在整个童年时期与他们不断治疗的儿童的抑制。这项研究具有可观的公共卫生益处，因为它将是第一个治疗刺激性诱导生长抑制的随机对照试验。此外，它将增强对与ADHD相关的生长异常的理解，而与持续使用扩展释放刺激物以及刺激性诱导诱导生长抑制背后的机制相关的生长异常。