Cortical Metrics Assessment Outcome Measure Development in Autism With Memantine Treatment

Development Of Cortical Metrics Assessment Outcome Measures in Response to Memantine Treatment in Autism Spectrum Disorders

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.

Study Overview

• Status: Withdrawn
• Conditions: Autism Spectrum Disorders
• Intervention / Treatment: Drug: Memantine-XR

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 Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

15 boys with ASD (8-12 years old) will receive Memantine XR®.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Memantine-XR; Boys ages 8-12 with ASD treated with Memantine-XR daily for 8 weeks	Drug: Memantine-XR; Participants will begin with 7mg Memantine XR® daily for a minimum of one week before increasing to an optimal dose of 14 mg daily. It is suggested that participants be titrated to the optimal dose by week 2 so that they may remain on 14mg for at least 6 weeks. Morning dosing is suggested, but can be flexible.; Other Names: Namenda-XR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cortical metrics (a mathematical plot of tactile responsivity in 3 dimensions)	a mathematical plot of tactile responsivity in 3 dimensions	8 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Linmarie Sikich, MD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013845. doi: 10.1002/14651858.CD013845.pub2.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: January 27, 2015
• First Submitted That Met QC Criteria: January 30, 2015
• First Posted (Estimate): February 2, 2015

Study Record Updates

• Last Update Posted (Actual): May 8, 2017
• Last Update Submitted That Met QC Criteria: May 3, 2017
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: autism spectrum disorders; memantine; cortical metrics; sensory testing
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: 14-1996