Quantification of the Antidyskinetic Effect of Amantadine and Topiramate in Parkinson's Disease

Nearly all Parkinson's disease (PD) patients eventually develop abnormal and unwanted
movements (dyskinesias) caused by the gold standard treatment, Levodopa. The severity of
these movements can range from subtle to extremely debilitating and may or may not interfere
with normal activities such as putting on a coat or brushing ones teeth. Currently, one of
the very few treatments for these unwanted and involuntary movements is Amantadine. New
options to treat dyskinesia would be clinically very valuable. In a previous study, we
developed an objective measuring device to quantify dyskinesia.

All PD participants will receive all three of the drug treatment intervention (placebo,
Amantadine 300 mg, Amantadine 300 mg plus Topiramate 150 mg). After 2 weeks of one drug
treatment, the participants will complete an overnight visit at the OCTRI Inpatient unit.
During the next day, participants will complete a mental task while standing on a force plate
for one minute every half hour until the end of the study. A levodopa IV infusion will occur
from 0900 to 1100. The subjects will be split into 'high' and 'low' dose groups. Those who
take <50 mg/hour of oral levodopa or levodopa equivalents will be considered 'low' dose
subjects and will receive 1 mg/kg/hr of IV Levodopa during the study visits (1, 2, and 3).
Those who administer > 50 mg/hr of oral levodopa to themselves normally will be considered
'high' dose subjects and will received 1.5 mg/kg/hr levodopa. Both groups will receive the
infusion for two hours from 0900 - 1100. The study drug will be taken orally at 0800.

Inclusion Criteria:

- Parkinson's Disease

- At least 21 years of age

- Must be taking Oral levodopa

- Must have dyskinesias by history or previous clinical observation

Exclusion Criteria:

- Significant cognitive impairment as measured by the Montreal Cognitive Assessment
(MOCA) score of < 25

- Subjects with unstable medical or psychiatric conditions (including hallucinations)

- Use of dopamine receptor blocking medications (e.g., neuroleptics, certain
antiemetics, tetrabenazine)

- History of unstable medical conditions (ie active cardiovascular disease, recent
unwellness or surgery etc.)

- Use of anticoagulants

- Current substance abuse

- Previous adverse event on amantadine