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临床试验/NCT04349917
NCT04349917已完成4 期

Large-scale Brain Organization During Cognitive Control in ADHD

University of North Carolina, Chapel Hill1 个研究点 分布在 1 个国家目标入组 37 人开始时间: 2016年12月16日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
入组人数
37
试验地点
1
主要终点
Resting State Brain Network Organization

研究概览

简要总结

The purpose of this study is to test whether children with attention-deficit/hyperactivity disorder (ADHD) are impaired in the ability to flexibly adapt brain network organization in response to shifting cognitive demands during the exertion of cognitive control, by assessing changes in network dynamics resulting from stimulant administration in children with ADHD, and how those changes relate to behavioral and symptom improvements. Subjects will be children with ADHD aged 8-12. Subjects will participate in multiple testing sessions that include: diagnosis and eligibility screening, neuropsychological and behavioral testing, and, if eligible, MRI scans and a medication challenge. Children with ADHD who are enrolled in the medication challenge will undergo one MRI scan on placebo and one MRI scan on stimulant medication, counterbalanced and double-blind. Functional connectivity will be measured using functional MRI and innovative graph theoretical analytic tools will be implemented. Network metrics will be related to symptomatology and behavioral testing measures. It is hypothesized that stimulant administration in children with ADHD will increase flexibility in network reconfiguration in response to changing cognitive control demands as compared to when they are on placebo. It is further hypothesized that the degree to which brain network organization is changed will be related to the degree of improvement in cognitive control performance.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Basic Science
盲法
Double (Participant, Investigator)

盲法说明

The pharmacy that provides the drug/placebo works from a randomized subject order defining whether each subject received drug first or placebo first. Only the pharmacists know this order, and the drug and placebo look identical to the participants and the investigators.

入排标准

年龄范围
8 Years 至 12 Years(Child)
性别
All
接受健康志愿者

入选标准

  • Between 8-12 years old
  • Diagnosis of ADHD (for ADHD group); ADHD group only can have comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnoses of oppositional defiant disorder, conduct disorder, depressive disorders, or anxiety disorders
  • ADHD subjects must never have been treated with medication for their ADHD

排除标准

  • Wechsler Intelligence Scale for Children-Fifth Edition Full-Scale Intelligence Quotient (IQ) < 80
  • Wechsler Individual Achievement Test-Third Edition Word Reading < 85
  • Any neurologic or developmental disabilities
  • Any reading or learning disabilities
  • Visual impairment that cannot be corrected-to-normal
  • Color blindness
  • Documented hearing impairment greater than 25 decibels (dB) loss in either year
  • Have already gone through puberty (Tanner Stage II or higher)
  • Medical contraindication to MRI
  • Any psychoactive medication

研究组 & 干预措施

Placebo, then Methylphenidate

Placebo Comparator

All children with ADHD in this study will receive one dose of methylphenidate and one dose of placebo over the course of two sessions approximately one week apart (order randomized and double-blind).

干预措施: Methylphenidate (Drug)

Placebo, then Methylphenidate

Placebo Comparator

All children with ADHD in this study will receive one dose of methylphenidate and one dose of placebo over the course of two sessions approximately one week apart (order randomized and double-blind).

干预措施: Placebo (Other)

Methylphenidate, then Placebo

Experimental

All children with ADHD in this study will receive one dose of methylphenidate and one dose of placebo over the course of two sessions approximately one week apart (order randomized and double-blind).

干预措施: Methylphenidate (Drug)

Methylphenidate, then Placebo

Experimental

All children with ADHD in this study will receive one dose of methylphenidate and one dose of placebo over the course of two sessions approximately one week apart (order randomized and double-blind).

干预措施: Placebo (Other)

结局指标

主要结局

Resting State Brain Network Organization

时间窗: 1 to 3 hours after administration of intervention

Assessment of network topology during a resting state using functional connectivity estimates. Modularity will be determined by applying graph theoretical methods to functional connectivity estimates acquired during functional magnetic resonance imaging (fMRI) scans. Modularity is measured on a -1 to 1 scale, with higher scores indicating stronger community structure, or a stronger tendency of clusters of brain regions to separate into distinct, highly interconnected networks with sparse connections across networks. The optimal modularity value depends on the context. For example, during complex tasks lower modularity is better, while during basic, automatic tasks higher modularity is better.

Task-Based Brain Network Organization

时间窗: 1 to 3 hours after administration of intervention

Assessment of network topology during the Go/No-go (GNG) regular and GNG reward tasks. Subjects see a series of sports balls and are told to respond to most balls (go trials), but not to some specific balls (no-go trials). GNG tasks are identical, except in the rewarded task, correct fast go responses and correct withholding on no-go trials are rewarded with 1 cent and 5 cents respectively. Graph theoretical methods are applied to functional connectivity estimates from fMRI scans to determine modularity during each task. Modularity (-1 to 1 scale) measures the degree to which the whole-brain system separates into distinct communities, such that greater modularity reflects stronger community structure, or stronger tendency of brain regions to separate into distinct, highly interconnected networks with few connections across networks. Optimal modularity value depends on context. During complex tasks lower modularity is better, while higher modularity is better for basic tasks.

Rest-Task Reconfiguration

时间窗: 1 to 3 hours after administration of intervention

Assessment of reconfiguration of network topology between the GNG regular task and the resting state and GNG reward task and resting state. In the GNG tasks, subjects see a series of sports balls and are told to respond to most of the balls (go trials), but not to some specific balls (no-go trials). GNG tasks are identical, except in the rewarded task, correct fast go responses and correct withholding on no-go trials are rewarded with 1 cent and 5 cents respectively. Normalized mutual information will be determined by applying the same graph theoretical methods to functional connectivity estimates acquired during fMRI scans for each rest-task pair. Normalized mutual information is measured on a 0 to 1 scale, with higher scores indicating more similarity in network structure across task and rest conditions.

Drug-induced Normalization

时间窗: 1 to 3 hours after administration of intervention

Assessment of how changes in brain network topology relate to improvements in behavioral performance on the GNG regular and reward tasks, in which subjects respond to go stimuli and withhold responses to no-go stimuli. GNG tasks are identical, except subjects are rewarded for good performance on the reward task. Brain measures include change in modularity during rest, GNG regular, and GNG reward (Outcome Measures 1, 2); behavioral measures include change in commission rate, omission rate, and coefficient of variation of response time during GNG tasks (Outcome Measures 5-7). Pearson correlations are used to relate change in brain measures with change in behavioral measures from the placebo to the methylphenidate scans. Positive correlations indicate that subjects with greater change in the brain measure had greater change in the behavioral measure. Negative correlations indicate that subjects with less change in the brain measure had greater change in the behavioral measure.

次要结局

  • Go/No-go (GNG) Commission Rate(1 to 3 hours after administration of intervention)
  • Go/No-go (GNG) Omission Rate(1 to 3 hours after administration of intervention)
  • Go/No-go (GNG) Response Time Variability(1 to 3 hours after administration of intervention)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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