Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
2020年7月7日 更新者：Jeffrey Newcorn、Icahn School of Medicine at Mount Sinai
The growing number of medications used to treat attention-deficit/hyperactivity disorder (ADHD) raises important questions about whether different medications have similar or different therapeutic mechanisms of action.
We have recently shown that the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline cingulate-precuneus regions.
These exciting findings offer a window into the common and unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments.
However, the interpretation and clinical utility of these results would be greatly enhanced by in-depth investigation of the impact of the two treatments on relevant neural networks, and analyses which evaluate whether improvement is achieved via normalization or other adaptive changes in brain function.
研究概览
详细说明
The specific aims of this project are to use functional magnetic resonance imaging (fMRI) to determine the significance of activation changes over treatment related to clinical improvement, and the impact of treatment on neural connectivity within and between the anti-correlated frontostriatal 'task-positive' circuit and cingulate-precuneus 'task-negative' network. Our central hypotheses are that clinical improvement is associated with: (i) normalization of reduced connectivity of regions within the 'task-positive' network, with resultant increased inhibition of motor cortex, and (ii) normalization of low task-related connectivity in regions within the task-negative network for MPH and the 'task-positive' network for ATX.
This research proposes to test a model which posits a neurophysiological basis of mechanisms of response to stimulant and non-stimulant medications, and fits with our long term objectives of being able to match treatments to individual patients. Testing this model requires large samples of youth scanned using fMRI before and after treatment, and matched healthy controls also scanned twice. We will use an innovative network-based approach to study the effects of treatment, building on results from our current fMRI treatment study, and incorporating new theoretical approaches to understanding ADHD and its treatment.
研究类型
介入性
注册 (实际的)
127
阶段
- 第四阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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New York
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New York、New York、美国、10029
- Icahn School of Medicine at Mount Sinai
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
7年 至 17年 (孩子)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
General inclusion criteria for subjects with ADHD and healthy controls are:
- aged 7-17 years;
- Wechsler Intelligence Scale for Children (WISC) scores ≥ 75;
- informed consent and assent to study participation.
Specific inclusion criteria for youth with ADHD are:
- diagnosis of ADHD, any subtype, determined by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Versions (K-SADS-PL);
- ADHD Rating Scale-IV-Parent Version: Investigator Administered (ADHD-RSIV) total score ≥ 1.5 SD above age and gender means for subtype
- Clinical Global Impressions-ADHD-Severity (CGI-S) score > 4;
- ADHD must be the primary diagnosis and focus of treatment, and the treatments offered in the study must not be contraindicated for the comorbid disorder.
Exclusion Criteria:
General exclusion criteria are:
- history of head injury with loss of consciousness or any CNS disease that is likely to affect brain function;
- diagnosis of autism or pervasive developmental, psychotic, major mood, and Tourette's disorder;
- alcohol or drug abuse in the past 3 months or a positive urinary toxic screen on initial evaluation;
- use of psychotropic medication within 2 weeks of the study (8 weeks for fluoxetine);
- pre-existing medical or psychological condition which precludes being in the scanner (e.g., claustrophobia, morbid obesity);
- metal in the body that precludes scanning (e.g., braces, metal plate);
- positive urine pregnancy test.
Specific exclusion criteria for the treatment trial include:
- previous unsuccessful trial of MPH or ATX that was adequately dosed (≥ 1 mg/kg for MPH or 1.0 mg/kg for ATX) and of adequate duration (≥ 4 weeks);
- abnormal findings on physical exam, or vital signs
- pulse and blood pressure > 95% of age and gender mean;
- inability to swallow capsules;
- weight is < 20 kg or > 85 kg.
Specific exclusion criteria for control youth include:
- no past history or current diagnosis of any psychiatric disorder, determined by the K-SADS-PL interview;
- ADHD-RS-IV and CBCL scores for each symptom domain ≤ 1 SD of age and gender means.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器：fMRI scans
Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart
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2 fMRI scans 6-8 weeks apart
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实验性的：Atomoxetine arm
These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.
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2 fMRI scans 6-8 weeks apart
Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks
其他名称：
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实验性的：Methylphenidate arm
Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.
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2 fMRI scans 6-8 weeks apart
Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task
大体时间：Baseline and at 6 weeks
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Comparison of Go-Nogo at 6 weeks from baseline.
Performance on a go-nogo task inside the scanner (fMRI).
In the go/no-go task, participants respond to certain stimuli ("go" stimuli) and make no response for others ("no-go" stimuli).
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Baseline and at 6 weeks
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)
大体时间：8 weeks
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ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.
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8 weeks
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Clinical Global Impressions-Severity (CGI-S)
大体时间：up to 6 weeks
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a clinician rated measure of symptom severity.
CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis.
Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
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up to 6 weeks
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Response Time in Attention Networks Test (ANT)
大体时间：baseline and at 6 weeks
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A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time.
The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control.
The response time were summed.
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baseline and at 6 weeks
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Continuous Performance Test (CPT)
大体时间：baseline and at 6 weeks
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A neuropsychological assessment of attention compared at 6 weeks from baseline.
CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented.
A fast reaction time and high commission error rate points to difficulties with impulsivity.
A slow reaction time with high commission and omission errors, indicates inattention in general.
Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score.
The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age.
A T-score of 50 is equal to the mean and is considered normal.
Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Higher values are indicative of more attention-related problems.
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baseline and at 6 weeks
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Digit Span
大体时间：baseline and at 6 weeks
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A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline.
Digit Span.
Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials.
Items may include words, numbers, or letters.
The task is known as digit span when numbers are used.
Memory span is a common measure of short-term memory.
A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2).
The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points.
Higher score indicates better health outcomes.
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baseline and at 6 weeks
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Finger Windows
大体时间：baseline and at 6 weeks
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A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline.
The Finger Windows subtest is a measure of nonverbal, rote sequential recall.
scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.
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baseline and at 6 weeks
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Kurt Schulz, PhD、Icahn School of Medicine at Mount Sinai
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2012年10月1日
初级完成 (实际的)
2018年4月30日
研究完成 (实际的)
2018年4月30日
研究注册日期
首次提交
2012年8月30日
首先提交符合 QC 标准的
2012年8月30日
首次发布 (估计)
2012年9月3日
研究记录更新
最后更新发布 (实际的)
2020年7月24日
上次提交的符合 QC 标准的更新
2020年7月7日
最后验证
2020年7月1日
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- GCO 11-0161
- 5R01MH095766-02 (美国 NIH 拨款/合同)
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.