Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Low Grade Glioma

Participants will be randomized to take part in one of two groups:

- The Memantine Group will be prescribed memantine at a dosage following FDA-approved
adult labeling. A low dose will initially be given beginning at least two weeks (± 7
days) prior to beginning radiation therapy. The dose will increase until participants
reach the target dose of 20 mg/day. Memantine will be given for a total of 12 weeks.

- The Placebo Group will be prescribed identical capsules with no active drug. The placebo
drug will be given in the same dose and frequency as described for the Memantine group.

Participants will undergo the same evaluations and monitoring throughout the medication
phase. Assessments will be done at baseline prior to study start, with follow-up assessments
at 6 weeks (end of radiation therapy), and 12 weeks (end of study medication). Psychological
testing to measure attention, working memory, problem solving, intelligence and academics
will be done for each participant. Caregivers will also complete questionnaires about
attention, problem solving, mood and interpersonal interactions. Caregivers will also be
asked to complete a questionnaire about the family's general characteristics and medical
history.

At the time points noted above, blood work, vital signs and echocardiograms will be obtained,
and the study neurologist will examine the participant to monitor side effects and
neurological functioning. A study nurse will contact the participant once per week during the
12 weeks of medication administration to identify possible medication-related side effects
and to check on rate of compliance with taking the medication. A remote app will be installed
on the participant's home computer or cell phone to help remind them to take the medication
and track success. At one year post medication, psychological and neurological examinations
will be repeated.

Inclusion Criteria:

- Age 6 years to 21 years at time of study enrollment

- Diagnosis of low grade glioma [e.g., pilocytic astrocytoma, optic pathway glioma,
ogligodendroglioma, ganglioglioma, pleomorphic xanthoastrocytoma (PXA)]

- Initiating cranial radiation therapy (photon or proton)

- Laboratory tests [transaminases (ALT, AST, ALP), BUN and creatinine not greater than
twice normal] and normal ECG

- Speak, read and understand English sufficiently to complete study assessments

- Adequate vision and hearing for valid completion of study measures

- Negative βHCG pregnancy test among females of childbearing age

- Participant must be able to swallow pills (psychology staff will be available to
assist with pill swallowing training if needed)

- Parent/Legal guardian available and able to speak, read and understand English

Exclusion Criteria:

- Medical disorder that would endanger subject's well-being (e.g., uncorrected
hypothyroidism, cardiac arrhythmia, hypertension requiring treatment, sick sinus
syndrome, prolonged QTc)

- History of significant neurological disease including poorly controlled seizures
(i.e., > 1 seizure per month; anti-epileptic medications are acceptable), stroke, or
head injury with loss of consciousness

- Psychiatric condition that would preclude or take precedence over study participation
(e.g., active psychosis, suicidal ideation)

- IQ below 70 based on baseline/screening assessment

- Treatment with psychotropic medication (psychostimulant, antidepressant, anxiolytic,
antipsychotic) within the past two weeks, unless being prescribed specifically as an
anti-emetic

- History of substance abuse

- History of hypersensitivity or reaction to NMDA receptor antagonists