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

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00794313
• Other study ID #: e4717
• Status: Terminated
• Phase: N/A
• First received: November 19, 2008
• Last updated: January 8, 2018
• Start date: September 2009
• Est. completion date: June 2010

Study information

• Verified date: January 2018
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Amantadine 300 mg
Amantadine, 300 mg, capsule, three times a day, two weeks
• Topiramate
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
• Sugar Pill
sugar pill, capsule, three times a day, 2 weeks

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

References & Publications (5)

da Silva-Júnior 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. Epub 2005 Sep 9. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)