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

Not Applicable

Terminated

Conditions: Parkinson's Disease

Interventions: Drug: Amantadine 300 mg
Drug: Sugar Pill
Drug: Topiramate

Registration Number: NCT00794313

Lead Sponsor: Oregon Health and Science University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Amantadine	Amantadine 300 mg	-
Sugar Pill	Sugar Pill	-
Amantadine plus Topiramate	Amantadine 300 mg	-
Amantadine plus Topiramate	Topiramate	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Modified Abnormal Involuntary Movement Scale Area Under the Curve	Measured every 1/2 hour for a levodopa dose cycle (starting 1 hour prior to infusion and ending 4 hours post 2-hour infusion)	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.