Anomalous Motor System Physiology in Attention Deficit Hyperactivity Disorder: Biomarker Validation and Modeling Domains of Function
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 214
- 试验地点
- 4
- 主要终点
- Transcranial Magnetic Stimulation (TMS)-evoked Short Interval Cortical Inhibition (SICI) Test-Retest Reliability
研究概览
简要总结
Attention-Deficit/Hyperactivity Disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder in childhood. Children with ADHD struggle in school due to problems with attention and high levels of impulsivity and hyperactivity. They are at substantially increased risk for long-term difficulties into adulthood, including academic underachievement, substance abuse, and criminal behavior. The diagnosis of ADHD, which is based on subjective ratings by parents and teachers, likely results from multiple different, overlapping differences in circuits of the brain responsible for attention and impulse control. However, we do not have any scientific or clinical tests that allow us to understand these circuits. In an effort to improve ADHD outcomes, we have used a technology called Transcranial Magnetic Stimulation (TMS) to identify highly reliable measurements of brain function. We have identified two very promising measures that are abnormal in children with ADHD and, importantly, also predict the severity of ADHD behaviors. The goal of this project is to determine if these two TMS measurements could be used to help better guide ADHD treatment. To do this, we will perform three investigations in 8 to 12 year old children to determine: 1) test-retest reliability; 2) pharmacologic responsiveness; and 3) correlations with two domains of function relevant to ADHD: "Cognitive Control" and "Emotional Valence." Through these investigations, we aim to determine whether these two TMS brain measures are reliable and meaningful enough to be used to help improve precision of individually-targeted and effective ADHD treatments.
详细描述
4.2. NARRATIVE STUDY DESCRIPTION
Summary This is a randomized, blinded, placebo-controlled, single-dose crossover study. The objective is to estimate, in a rigorous, unbiased manner, the effect of 10 mg methylphenidate (MPH) on two putative biomarkers of ADHD, measured using Transcranial Magnetic Stimulation (TMS). Two other aims of this larger study, quantifying test-retest reliability and linking TMS biomarkers to RDoC domains of cognitive control and emotional valence, are not directly part of the clinical trial and are fully described in the research strategy.
Doctors use observations and subjective rating scales both to diagnose Attention Deficit Hyperactivity Disorder (ADHD) and to make decisions about medical or behavioral treatments. This study addresses the possibility that in children with ADHD, brain-based measurements, or biomarkers, could be useful for diagnosis and treatment decisions. These biomarkers are Short Interval Cortical Inhibition (SICI) and Task-Related Up-Modulation (TRUM). These biomarkers may allow clinicians to identify that a child has a "type" of ADHD which might respond more effectively to treatments that are precisely and individually targeted. Thus it is important to estimate the effects of commonly prescribed treatments on SICI and TRUM. This protocol aims to determine the effects of a single 10 mg dose of MPH, a stimulant medication widely prescribed to treat ADHD, on SICI and TRUM.
Assignment of participants For each child with ADHD, participation in the study will consist of three visits. Treatment occurs as a single dose on visits 2 and 3. All participants will receive both placebo and 10 mg MPH. Order will be counterbalanced.
Population Sample At the two study sites, Cincinnati Children's Hospital Medical Center (CCHMC) and the Kennedy Krieger Institute (KKI), we will recruit 144 pre-pubescent children, ages 8 years 0 months to 12 years 11 months, with ADHD. We estimate a total of 120 participants will participate in the full study. All recruitment methods will conform to CCHMC Institutional Review Board (IRB) and HIPAA requirements. The study will be approved by the CCHMC Institutional IRB. Children with ADHD will be primarily recruited through community resources, including local chapters of the Children with ADHD (CHADD), local public and private schools, as well as multiple clinics at CCHMC and KKI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Preparation of identical single dose capsules of methylphenidate and placebo prepared by study pharmacy.
入排标准
- 年龄范围
- 8 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Either gender, any race, ethnicity or socioeconomic status
- •Currently between 8 years 0 months and 12 years, 11 months, 30 days
- •Willing to answer questions about ADHD and related diagnoses
- •For children with ADHD prescribed stimulant medications, willing to suspend taking medications as specified in the study procedures
- •For children with ADHD, willing to participate in the single dose, randomized crossover study to probe acute effects of methylphenidate on biomarkers
- •Right hand dominant (predominately right-handed)
- •Able to participate in and sign an informed consent
- •ADHD inclusion: The diagnosis of ADHD will be based on Diagnostic and Statistical Manual version 5 (DSM-5) criteria using standard rating scales and a structured diagnostic interview. Oppositional Defiant Disorder is permitted; Conduct disorder is excluded.
- •Typically Developing (healthy control) inclusion: Free of ADHD or other developmental or psychiatric disorders based on DSM-5 criteria using standard rating scales and a structured diagnostic interview.
排除标准
- •Known diagnosis of mental retardation, cerebral palsy, Autism Spectrum Disorder, traumatic brain injury, brain tumor, epilepsy, or other serious neurological disorder.
- •Major Depression, Bipolar Disorder, Conduct Disorder, Adjustment Disorder, other Anxiety Disorders, or other developmental psychiatric diagnoses.
- •For females, onset of menses, pregnancy.
- •Current use of antidepressants, non-stimulant ADHD medications, dopamine blocking agents, mood stabilizers.
- •Implanted brain stimulator, vagal nerve stimulator, ventriculo-peritoneal shunt, cardiac pacemaker, or implanted medication port.
- •Diagnosis of a speech/language disorder or a Reading Disability (RD).
研究组 & 干预措施
Attention Deficit Hyperactivity Disorder (ADHD)
8 to 12 year old children diagnosed with ADHD. Randomized, blinded, single dose, placebo controlled, crossover trial.
干预措施: Placebo (Drug)
Attention Deficit Hyperactivity Disorder (ADHD)
8 to 12 year old children diagnosed with ADHD. Randomized, blinded, single dose, placebo controlled, crossover trial.
干预措施: Methylphenidate (Drug)
结局指标
主要结局
Transcranial Magnetic Stimulation (TMS)-evoked Short Interval Cortical Inhibition (SICI) Test-Retest Reliability
时间窗: less than one month
A ratio of amplitudes of motor evoked potentials from paired (inhibitory) and single TMS pulses, obtained from dominant motor cortex with hand at rest
Transcranial Magnetic Stimulation (TMS)-evoked Task Related Up Modulation (TRUM) Test-Retest Reliability
时间窗: less than one month
A ratio of amplitudes of motor evoked potentials during engagement in a response inhibition task versus rest, obtained from dominant motor cortex
次要结局
未报告次要终点
研究者
Donald Gilbert, MD, MS, FAAN, FAAP
Professor
Children's Hospital Medical Center, Cincinnati