Predicting Treatment Response to Memantine in Autism Using Magnetic Resonance Spectroscopy

Study 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.

Primary Outcome

Clinician rated 7 item scale looking at improvements in specific aspects and overall level of autism

Interventions

• DEVICE Magnetic Resonance Imaging
• DRUG Memantine