Clinical trial NCT02212275: Cortical Metrics in Intervention Trials With Autism Spectrum Disorders
Official title: Initial Development of Cortical Metrics, an Objective, Physiologically-Based Outcome Measure, for Intervention Trials in Autism Spectrum Disorders (ASD)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Autism Spectrum Disorders
Keywords: ASD
autism
typical development
sensory testing
the cortical metric
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: North Carolina Translational and Clinical Sciences Institute
First posted: 2014-08-08
Enrollment: 0
Sex: MALE
Minimum age (years): 8
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: 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.

Detailed description: 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.

Specific Aim 3: Obtain preliminary proof of mechanism data that the cortical metric assesses the excitatory: inhibitory balance of intra-cortical connections by examining the effect of acute exposure to dextromethorphan (DXM), which transiently blocks one type of excitatory neurotransmission

Hypothesis 3: DXM will alter the cortical metric consistent with reduced adaptation.

The completion of these aims will be essential to design a larger federally funded trial to validate the cortical metric as an outcome measure in a more heterogeneous pediatric ASD sample. Specifically, we will aim to demonstrate that 1) the cortical metric differs between children with ASD and with normal development, 2) that the cortical metric has minimal variability over time in the absence of fno major changes in brain function, and 3) that the cortical metric changes in response to a specific, temporary reduction in excitatory stimulation caused by a single DXM dose.

A larger grant could focus on determining how sensitive and clinically relevant changes in the cortical metric are.

If we are not able to demonstrate the potential for the cortical metric to be changed by agents that reduce excitatory stimulation acutely or if the variability of the cortical metric over 3 weeks is too great, no further examination of the cortical metric as an outcome measure in ASD trials would be pursued. If there are not differences in the cortical metric of children with and without ASD, we would be less interested in further examining the cortical metric.

Eligibility criteria: Group 1 Typically Developing Youth: We will recruit 30 typically developing boys 8-12 years old to participate in a screening visit, and two tactile perception sessions (visit 1 and 2).

Inclusion Criteria:

* Healthy Male Boys ages 8-12
* Normal developmental milestones and school performance
* Primary caretaker is able to participate in study appointments as is indicated

Exclusion Criteria:

* 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)

Primary outcomes:
measure: The difference in the Cortical Metric before and after acute exposure to dextromethorphan (DXM)
timeFrame: 2 hours after DXM exposure and 20 min before DXM
measure: Change in the cortical metric
timeFrame: 3 weeks
measure: The Cortical Metric
timeFrame: Baseline = time 0
Secondary outcomes:
measure: Aberrant Behavior Checklist (ABC) Total Score
timeFrame: time 0 (baseline)
measure: Pervasive Developmental Disorders Behavior Inventory - Screening Version Score (PDDBI-SV) Social Deficit Score
timeFrame: Baseline = time 0
measure: Social Responsiveness Scale, Version 2 Total Score (SRS)
timeFrame: Time 0 = Baseline
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Center for Autism and Brain Development
state: North Carolina
Study officials:
affiliation: Duke University
name: Linmarie Sikich, MD
role: PRINCIPAL_INVESTIGATOR
References: