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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Amantadine 300 mg
* Drug: Topiramate
* Drug: Sugar Pill


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amantadine<br> | Drug: Amantadine 300 mg<br>* Amantadine, 300 mg, capsule, three times a day, two weeks<br>|
| Experimental: Amantadine plus Topiramate<br> | Drug: Amantadine 300 mg<br>* Amantadine, 300 mg, capsule, three times a day, two weeks<br>Drug: Topiramate<br>* Topiramate, 25 mg, capsule, two times a day, 1 week Sugar Pill, capsule, one time a day, 1 week Topiramate, 50 mg, capsule, three times a day, 1 week<br>* Other names: Topamax;|
| Placebo Comparator: Sugar Pill<br> | Drug: Sugar Pill<br>* sugar pill, capsule, three times a day, 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forceplate AUC | Area under the curve for the root mean squared velocity in the anterior-posterior direction as measured by a forceplate. | Every 1/2 hour for 8 hour levodopa cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Abnormal Involuntary Movement Scale Area Under the Curve | Area under the curve computed for whole body (total) mAIMS (Modified Abnormal Involuntary Movement Scale) scores at each time measurement. This is a commonly utilized scale that is completed by an observer who judges the severity of levodopa induced dyskinesia (LID) in 7 body parts (face, neck, trunk, both legs, and both arms). All body parts are rated separately on this 0 (none) to 4 (severe - markedly impairs activities) scale. Thus, the total score can range from 0 - 28 with 28 indicating the most severe LID. mAIMS ratings occur as the subject performs the cognitive task while standing on the force plate. mAIMS ratings are made every half hour during the levodopa (LD) dose cycle. | Measured every 1/2 hour for a levodopa dose cycle (starting 1 hour prior to infusion and ending 4 hours post 2-hour infusion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinsons disease, dyskinesia, amantadine, efficacy