Clinical trial NCT00794313: Quantification of the Antidyskinetic Effect of Amantadine and Topiramate in Parkinson's Disease
Official title: Quantification of the Antidyskinetic Effect of Amantadine and Topiramate in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Parkinsons disease
dyskinesia
amantadine
efficacy
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2008-11-20
Enrollment: 3
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Forceplate AUC
timeFrame: Every 1/2 hour for 8 hour levodopa cycle
Secondary outcomes:
measure: Modified Abnormal Involuntary Movement Scale Area Under the Curve
timeFrame: Measured every 1/2 hour for a levodopa dose cycle (starting 1 hour prior to infusion and ending 4 hours post 2-hour infusion)
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health & Science University, Portland VA Medical Center
name: Kathryn Chung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health & Science Unversity
name: John G Nutt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Snow BJ, Macdonald L, Mcauley D, Wallis W. The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study. Clin Neuropharmacol. 2000 Mar-Apr;23(2):82-5. doi: 10.1097/00002826-200003000-00004.
citation: Verhagen Metman L, Del Dotto P, van den Munckhof P, Fang J, Mouradian MM, Chase TN. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. Neurology. 1998 May;50(5):1323-6. doi: 10.1212/wnl.50.5.1323.
citation: Del Dotto P, Pavese N, Gambaccini G, Bernardini S, Metman LV, Chase TN, Bonuccelli U. Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study. Mov Disord. 2001 May;16(3):515-20. doi: 10.1002/mds.1112.
citation: Hagell P, Widner H. Clinical rating of dyskinesias in Parkinson's disease: use and reliability of a new rating scale. Mov Disord. 1999 May;14(3):448-55. doi: 10.1002/1531-8257(199905)14:33.0.co;2-0.
citation: da Silva-Junior FP, Braga-Neto P, Sueli Monte F, de Bruin VM. Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study. Parkinsonism Relat Disord. 2005 Nov;11(7):449-52. doi: 10.1016/j.parkreldis.2005.05.008. Epub 2005 Sep 9.