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

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

Levodopa is the main drug treatment for Parkinson's disease. Levodopa can cause unwanted and uncontrolled movements called dyskinesias. A drug called amantadine can reduce these movements. To date, there are no objective measures of these movements. The purpose of this study is to measure the reduction of the movements by amantadine and/or topiramate using an objective measure.

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