Predicting Treatment Response to Memantine in Autism Using Magnetic Resonance Spectroscopy

Summary

Memantine, an N-methyl-D-aspartate receptor antagonist, has been explored as a possible therapeutic agent that reduces the excitatory (glutamate) - inhibitory (gamma amino-butyric acid, GABA) imbalance in autism pathology and improves social and communication deficits. While some studies have shown positive results, a large clinical trial failed to show benefit possibly because different subsets of autism responded differently to the treatment.

The investigator proposes a pilot, exploratory, clinical follow-on study using proton magnetic resonance spectroscopy (1H-MRS) to determine whether baseline glutamate/GABA levels in certain regions of the brain may help predict treatment response to Memantine in autistic subjects. At study onset, subjects will be assessed on the behavioral scales such as the Aberrant Behavior Checklist and Clinical Global Impressions scale, followed by MRS imaging. Memantine treatment will be started post imaging. Assessment measures will be repeated at week 12 during treatment. Glutamate and GABA levels in brain regions will be correlated to improvements on assessment measures. Expected results include higher glutamate and/or lower GABA levels in the anterior cingulate cortex at baseline in responders to memantine. If the hypotheses are confirmed, it will provide evidence of a relevant neural biomarker to predict treatment response to memantine with important implications for clinical care including improving individualization of treatments.

Conditions

• Autism Spectrum Disorder

Interventions

DRUG

Memantine

Namenda (pill and the liquid) will be started at 5 mg/day doses to be titrated up 20 mg/day based on response and tolerability, as per the package insert instructions and based upon clinical titration in other clinical trials for a period of 12 weeks. Namenda XR will be started at 7 mg/day to be titrated up to 28mg/day based on response and tolerability, as per package insert instructions and based upon clinical titration in other clinical trials for a period of 12 weeks.

DEVICE

Magnetic Resonance Imaging

The subjects will undergo an MRI assessment after baseline behavioral assessment. The session will involve a structural MRI scan, single voxel spectroscopy scans and resting state functional MRI. The subjects will be started on memantine post the imaging session. The imaging will be carried out on a research dedicated 3 Tesla (3T) Siemens Trio Scanner at the University of Missouri Brain Imaging Center by trained personnel.

Sponsors & Collaborators

• University of Missouri-Columbia

  lead OTHER

Principal Investigators

• David Q Beversdorf, MD · University of Missouri-Columbia

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-06-30

Primary Completion

2021-04-30

Completion

2021-04-30

Countries

• United States

Study Locations