Cortical Metrics in Intervention Trials With Autism Spectrum Disorders

NCT ID: NCT02212275

Last Updated: 2016-08-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2016-07-31

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.

Conditions

Autism Spectrum Disorders

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dextromethophan

Intervention Type: DRUG

A single age and weight appropriate dose of over the counter Delsym Cough Syrup containing only DXM as an active ingredient.

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.

Group Type: ACTIVE_COMPARATOR

Dextromethophan

Intervention Type: DRUG

A single age and weight appropriate dose of over the counter Delsym Cough Syrup containing only DXM as an active ingredient.

Interventions

Dextromethophan

A single age and weight appropriate dose of over the counter Delsym Cough Syrup containing only DXM as an active ingredient.

Intervention Type: DRUG

Other Intervention Names

Delsym Cough Syrup

Eligibility Criteria

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

• 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

• 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.

• 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)

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

North Carolina Translational and Clinical Sciences Institute

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linmarie Sikich, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States

Duke Center for Autism and Brain Development

Durham, North Carolina, United States

Countries

United States

Other Identifiers

14-1141

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00065239

Identifier Type: -

Identifier Source: org_study_id