Cortical Metrics in Intervention Trials With Autism Spectrum Disorders

Autism Spectrum Disorders Clinical Trial

Official title: Initial Development of Cortical Metrics, an Objective, Physiologically-Based Outcome Measure, for Intervention Trials in Autism Spectrum Disorders (ASD)

Status Withdrawn

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autism Spectrum Disorders
• Autistic Disorder
• Child Development Disorders, Pervasive
• Disease

• NCT number: NCT02212275
• Study type: Interventional
• Source: Duke University
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: August 2015
• Completion date: July 2016