Cortical Metrics Assessment Outcome Measure Development in Autism With Memantine Treatment

Withdrawn

• Conditions: Autism Spectrum Disorders
• Interventions: Drug: Memantine-XR

• Registration Number: NCT02353130
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

Specific Aim 1: Obtain proof of concept evidence that cortical metrics will change in response to treatment with Memantine extended release (XR)®, an agent that modulates n-methyl d-asptartate (NMDA) receptor activation, in children with autism spectrum disorders (ASD) who clinically demonstrate treatment response.

Hypothesis1: Children with ASD who have dramatic clinical response to Memantine XR® will exhibit changes in their cortical metrics, which will differ less from neurotypical children. Subjective ratings of improvement will be correlated with the change in cortical metrics.

The completion of these aims will be essential to design a larger federally funded trial to validate cortical metrics as an outcome measure in a more heterogeneous pediatric ASD sample. Specifically, the feasibility data obtained may demonstrate the potential for detecting changes in cortical metrics over time, so that a larger grant could focus on determining how sensitive and clinically relevant changes in cortical metrics are or may indicate the need to explore different interventions to use in a validation study. We have chosen to use Memantine XR® because of its impact on NMDA neurotransmission, its current evaluation in a large multi-site randomized ASD clinical trial whose initial results are expected shortly, and our own observations of clinical improvements and good tolerability in the ongoing trial.

Detailed Description

Youth with ASD ages 8-12 years will undergo cortical metrics testing (testing of ability to discriminate the vibration of small brushes on the tops of the hand under various conditions) prior to treatment with memantine XR. They will then be treated with memantine XR target dose of 14milligrams daily for 8 weeks. At the end of 8 weeks, cortical metrics testing will be repeated. Within-subject changes in the cortical metrics testing between baseline and endpoint will be examined and described. Potential relationships between changes in clinical rating scales and cortical metrics will be examined. Data will be utilized to inform a decision about continuing to explore the utility of cortical metrics to detect changes in brain function in youth with ASD in response to therapeutic interventions.

Study Timeline

• Study First Submitted: 2015-01-27
• Study First Submitted QC: 2015-01-30
• Study First Posted: 2015-02-02
• Study Start: 2015-07
• Status Verified: 2015-10
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Last Update Submitted: 2017-05-03
• Last Update Posted: 2017-05-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

• Male Boys ages 8-12 with ASD (confirmed with ADOS-2 and DSM-5 checklist at screening)
• 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

• No new educational or behavioral intervention within 4 weeks of baseline.
• No history of non-febrile seizures, other neurological disorders, or comorbid psychiatric disorders.
• Impairment of renal function
• Evidence or history of malignancy
• Any significant medical conditions including but not limited to hematological, endocrine, respiratory, hepatic, cardiovascular or gastrointestinal disease
• Patients who, in the investigator's opinion, might not be suitable for the study
• Significant risk of suicidality based on investigator judgment
• History of hypersensitivity reaction to Memantine, dextromethorphan, amantadine or any other NMDA antagonists
• Changes in psychotropic medications within 4 weeks of baseline visit

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Memantine-XR	Memantine-XR	Boys ages 8-12 with ASD treated with Memantine-XR daily for 8 weeks

Primary Outcome Measures

Name	Time	Method
cortical metrics (a mathematical plot of tactile responsivity in 3 dimensions)	8 weeks	a mathematical plot of tactile responsivity in 3 dimensions

Secondary Outcome Measures

Name	Time	Method
PDD-BI SV change 0-8	8 weeks	18 item caregiver completed questionnaire about social functioning
ABC-SW subscale score 0-8	8 weeks	13 item caregiver completed questionnaire about social problems
Clinical Global Impressions - Improvement Score.	8 weeks	ratings of 1 or 2 indicate clinically meaningful response