Initial Development of Cortical Metrics, an Objective, Physiologically-Based Outcome Measure, for Intervention Trials in Autism Spectrum Disorders (ASD)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- The Cortical Metric
研究概览
简要总结
The investigators overarching aim is to obtain preliminary data to support a larger grant to validate a novel objective, physiologically-based outcome measure for clinical trials in autism spectrum disorders (ASDs) called the cortical metric. Absence of such an outcome measure has greatly hindered the development of treatments for core symptoms of ASD.
详细描述
The cortical metric is a single numeric measurement that is calculated using a multi-parametric mathematical approach from a series of measurements of the speed, intensity, diameter, and distance between two vibrations with which a person reacts to and can distinguish vibrations from small brushes that touch the top side of fingers on the left hand under multiple conditions designed to elicit cortical adaptation The cortical metric is based on the neurobiological principle that the nerves in the fingertips project to adjacent groups of neurons that work together to continuously optimize perceptions of touch under varying conditions. Such perceptual optimization reflects the shifting excitatory and inhibitory actions of individual neurons. We hypothesize that the brain's processing of vibration is similar to its processing of other kinds of information. We also hypothesize that in people with ASD adjacent groups of neurons work together less well to process information.
Specific Aim 1: Obtain evidence regarding the ability of the "cortical metric" to distinguish between 8-12 year-olds with typical development and with high functioning autism spectrum disorders (ASDs).
Hypothesis 1: The cortical metric of children with ASD will differ from that of age matched, typically developing children. This difference will be consistent with lower than normal local functional connectivity.
Specific Aim 2: Validate the test-retest reliability of the cortical metric by examining its stability of over an average of 3 weeks with no intervening interventions in both groups of children.
Hypothesis 2: Test-retest reliability will be highly correlated in both groups of children.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 12 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy Male Boys ages 8-12
- •Normal developmental milestones and school performance
- •Primary caretaker is able to participate in study appointments as is indicated
排除标准
- •Significant lifetime medical history including non-febrile seizures, neurological problems, psychiatric problems or learning disabilities
- •Any sensory impairment (i.e. deafness or blindness)
- •1st or 2nd degree family members with a history of ASD
- •1st or 2nd degree family members with ADHD or other developmental problems
- •Adverse reaction to dextromethorphan
- •Inability to successfully complete and fully understand the reaction time subtest (cortical metrics)
- •Group 2 Youth with ASD: 8-12 years old: > 30 boys will be recruited who have a known or suspected diagnosis of ASD confirmed by DSM-5 checklist and the ADOS-2 at screening.
- •Inclusion Criteria:
- •Male Boys ages 8-12 with ASD (confirmed by DSM-5 checklist and the ADOS-2)
- •IQ's should be within the normal range (≥ 70) (by prior testing or Stanford Binet 5 at screening)
- •Primary caretaker is able to participate in study appointments as is clinically indicated
- •Ability of child to participate in all aspects of the protocol per investigator clinical judgment
- •Exclusion Criteria:
- •New educational or behavioral intervention within 4 weeks of baseline
- •History of non-febrile seizures, other neurological disorders, psychosis, bipolar disorder, or Tourette Syndrome.
- •Any sensory impairment (i.e. deafness or blindness)
- •Adverse reaction to dextromethorphan
- •Inability to successfully complete and understand the reaction time subtest (cortical metrics)
- •Changes in psychiatric medications within 4 weeks of baseline visit
- •Taking epileptic medication (including but not limited to carbamazepine, phenobarbital, Depakote, lamictal, oxycarbazepine, topiramate)
研究组 & 干预措施
Dextromethorphan in ASD
8-12 years old: > 30 boys will be recruited who have a known or suspected diagnosis of ASD confirmed by DSM-5 checklist and the ADOS-2 at screening. They will have the cortical metric measured 20 min prior to receiving DXM and 2 hours after receiving a single age and weight appropriate dose of DXM. The outcome reported is the difference in the cortical metric after the DXM dose and before the DXM dose.
干预措施: Dextromethophan (Drug)
Dextromethorphan in controls
30 typically developing boys 8-12 years old who have the cortical metric measured 20 min before receiving a single age and weight appropriate dose of DXM and 2 hours after the single dose of DXM. The reported value will be the difference between the cortical metric 2hrs after the single dose of DXM and the cortical metric 20 minutes prior to the single dose of DXM.
干预措施: Dextromethophan (Drug)
结局指标
主要结局
The Cortical Metric
时间窗: Baseline = time 0
The cortical metric will be measured at the baseline of the study = time 0. We will compare the mean cortical metric and the range of the cortical metric between the ASD and typically developing groups. This addresses Specific Aim 1 of the trial. There are 3 primary outcomes all involving the cortical metric because the tool will not be useful to detect treatment changes unless all three outcomes demonstrate the desired response. The goal of this aim is to replicate the findings of the John Hopkins University group that found differences in the cortical metric between groups of children 8-12 years old with ASD and with typical development.
Change in the cortical metric
时间窗: 3 weeks
The difference between the cortical metric measured 20 minutes before DXM treatment at visit 2, which occurs 3 weeks after the baseline = time 0 visit, and the cortical metric measured 3 weeks earlier at the baseline visit = time 0. We presume their will be no major changes in brain functioning over 3 weeks. This addresses Specific Aim 2 of the trial, regarding test retest stability. There are 3 primary outcomes all involving the cortical metric because the tool will not be useful to detect treatment changes unless all three outcomes demonstrate the desired response.
The difference in the Cortical Metric before and after acute exposure to dextromethorphan (DXM)
时间窗: 2 hours after DXM exposure and 20 min before DXM
At visit 2 the cortical metric will be measured 20 min prior to a single dose of DXM and 2hrs after the dose of DXM. . This addresses Specific Aim 3 of the trial. There are 3 primary outcomes all involving the cortical metric because the tool will not be useful to detect treatment changes unless all three outcomes demonstrate the desired response. Visit 2 occurs 3 weeks after baseline = time 0
次要结局
- Aberrant Behavior Checklist (ABC) Total Score(time 0 (baseline))
- Pervasive Developmental Disorders Behavior Inventory - Screening Version Score (PDDBI-SV) Social Deficit Score(Baseline = time 0)
- Social Responsiveness Scale, Version 2 Total Score (SRS)(Time 0 = Baseline)