Autism Spectrum DisordersPhase 2/3NCT02212275
Cortical Metrics in Intervention Trials With Autism Spectrum Disorders
A Phase 2/3 study testing Dextromethophan in people with Autism Spectrum Disorders, run by Duke University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 8 to 12 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorders
- What is being tested?
- Dextromethophan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2015to Jul 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 12 years
- Men only
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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)
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- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27517
Duke Center for Autism and Brain Development
Durham, North Carolina, 27710
About this study
Official title: Initial Development of Cortical Metrics, an Objective, Physiologically-Based Outcome Measure, for Intervention Trials in Autism Spectrum Disorders (ASD)
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.
Read the 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
- Being tested
- Dextromethophan
- Keywords
- ASD, autism, typical development, sensory testing, the cortical metric
- Medical subject headings
- Autism Spectrum Disorder, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DextromethophanDrug
Also called Delsym Cough Syrup
A single age and weight appropriate dose of over the counter Delsym Cough Syrup containing only DXM as an active ingredient.
| Study group | Role | What they receive |
|---|---|---|
| Dextromethorphan in ASD | Experimental | 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. Receives: Drug: Dextromethophan |
| Dextromethorphan in controls | Active comparator | 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. Receives: Drug: Dextromethophan |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference in the Cortical Metric before and after acute exposure to dextromethorphan (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
Measured: 2 hours after DXM exposure and 20 min before DXM
Change in the cortical metric
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.
Measured: 3 weeks
The Cortical Metric
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.
Measured: Baseline = time 0
Secondary outcomes (3)
Aberrant Behavior Checklist (ABC) Total Score
The ABC focuses on problem behaviors in five subdomains: irritability, attention, repetitive behaviors, unusual speech, and social withdrawal and will be completed by subject's parent/guardian or caregiver.
We will examine the correlation between the ABC Total score and the cortical metric.
Measured: time 0 (baseline)
Pervasive Developmental Disorders Behavior Inventory - Screening Version Score (PDDBI-SV) Social Deficit Score
The PDDBI-SV examines both adaptive and maladaptive behaviors related to autism. The adaptive items are reverse scored and then all items are summed to generate the social deficit score. It is not age specific. This questionnaire will be completed by subject's parent/guardian or caregiver. The correlation between the PDD-BI SV Social Deficit score and the cortical metric will be examined.
Measured: Baseline = time 0
Social Responsiveness Scale, Version 2 Total Score (SRS)
This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings (Constantino, Davis et al. 2003). Completed by a parent or teacher in just 15 to 20 minutes, the SRS provides a clear picture of a child's social impairments, assessing social awareness, social information processing, capacity for reciprocal social communication, social anxiety/avoidance, and autistic preoccupations and traits. It is appropriate for use with children from 4 to 18 years of age. The SRS measures impairment on a quantitative scale across a wide range of severity--which is consistent with recent research indicating that autism is best conceptualized as a spectrum condition rather than an all-or-nothing diagnosis. This will be completed by the subject's parent/guardian or caregiver.
The correlation between the SRS Total score and the cortical metric will be examined.
Measured: Time 0 = Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2014 (estimated)
- Study startAug 2015
- Primary completionJul 2016
- Study completionJul 2016
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisordersStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- North Carolina Translational and Clinical Sciences Institute
- Responsible party
- Sponsor
- Investigators
- Linmarie Sikich, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02212275
- Sponsor's protocol ID
- Pro00065239
- Other IDs
- 14-1141
- Status last verified
- Aug 2016
- First submitted
- 29 Jul 2014
- Last updated
- 25 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Initial Development of Cortical Metrics, an Objective, Physiologically-Based Outcome Measure, for Intervention Trials in Autism Spectrum Disorders (ASD)
- ClinicalTrials.gov ID
- NCT02212275
- Acronym / sponsor ID
- Pro00065239
- Conditions
- Autism Spectrum Disorders
- Keywords
- ASD, autism, typical development, sensory testing, the cortical metric
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- North Carolina Translational and Clinical Sciences Institute
- Study start
- Aug 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 8 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dextromethorphan in ASD | Experimental | Drug: Dextromethophan8-12 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. |
| Dextromethorphan in controls | Active comparator | Drug: Dextromethophan30 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. |
Who may qualify
- Ages
- 8 to 12 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DextromethophanAlso: Delsym Cough SyrupA single age and weight appropriate dose of over the counter Delsym Cough Syrup containing only DXM as an active ingredient. | Drug | Dextromethorphan in ASD, Dextromethorphan in controls |
Primary outcome
The difference in the Cortical Metric before and after acute exposure to dextromethorphan (DXM)
Time frame: 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
Change in the cortical metric
Time frame: 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 Cortical Metric
Time frame: 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.
3 secondary outcomes
Aberrant Behavior Checklist (ABC) Total Score
Time frame: time 0 (baseline)
Pervasive Developmental Disorders Behavior Inventory - Screening Version Score (PDDBI-SV) Social Deficit Score
Time frame: Baseline = time 0
Social Responsiveness Scale, Version 2 Total Score (SRS)
Time frame: Time 0 = Baseline
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linmarie Sikich, MD principal investigator
Duke University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dextromethophan in people with Autism Spectrum Disorders, run by Duke University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference in the Cortical Metric before and after acute exposure to dextromethorphan (DXM) (time frame: 2 hours after DXM exposure and 20 min before DXM). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2016.