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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Amantadine | Experimental |
| |
| Amantadine plus Topiramate | Experimental |
| |
| Sugar Pill | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amantadine 300 mg | Drug | Amantadine, 300 mg, capsule, three times a day, two weeks |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kathryn Chung, MD | Oregon Health & Science University, Portland VA Medical Center | Principal Investigator |
| John G Nutt, MD | Oregon Health & Science Unversity | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10803797 | Background | 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. | |
| 9595981 | Background | 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. |
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4 individuals were screened for this study. 3 participants were enrolled in the study. 1 participant screen failed due to inability to reduce/stop Amantadine.
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| ID | Title | Description |
|---|---|---|
| FG000 | Amantadine, Then Amantadine + Topiramate, Then Placebo | Amantadine: Amantadine 200 mg capsule two times a day (week 1); Amantadine 300 mg capsule three times a day (week 2) then 7 Days washout then Amantadine +Topiramate: Amantadine, 200 mg capsule, two times a day with Topiramate 25 mg capsule two times a day (week 1), then Amantadine 300 mg capsule three times a day with Topiramate 50 mg capsule two times a day (week 2) then 7 Days washout then Placebo: Sugar pill 2 capsule three times a day, 2 weeks |
| FG001 | Amantadine + Topiramate, Then Placebo, Then Amantadine | Amantadine +Topiramate: Amantadine, 200 mg capsule, two times a day with Topiramate 25 mg capsule two times a day (week 1), then Amantadine 300 mg capsule three times a day with Topiramate 50 mg capsule two times a day (week 2) then 7 Days washout then Placebo: Sugar pill 2 capsule three times a day, 2 weeks then 7 Days washout then Amantadine: Amantadine 200 mg capsule two times a day (week 1); Amantadine 300 mg capsule three times a day (week 2) |
| FG002 | Placebo, Then Amantadine, Then Amantadine + Topiramate | Placebo: Sugar pill 2 capsule three times a day, 2 weeks then 7 Days washout then Amantadine: Amantadine 200 mg capsule two times a day (week 1); Amantadine 300 mg capsule three times a day (week 2) then 7 Days washout then Amantadine +Topiramate: Amantadine, 200 mg capsule, two times a day with Topiramate 25 mg capsule two times a day (week 1), then Amantadine 300 mg capsule three times a day with Topiramate 50 mg capsule two times a day (week 2) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Amantadine 300 mg : Amantadine, 300 mg, capsule, three times a day, two weeks or 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 or Sugar Pill : sugar pill, capsule, three times a day, 2 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Forceplate AUC | Area under the curve for the root mean squared velocity in the anterior-posterior direction as measured by a forceplate. | triple cross-over study design. | Posted | Mean | Standard Deviation | (meters/second)*hours | Every 1/2 hour for 8 hour levodopa cycle |
|
6 Weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Amantadine | Amantadine 300 mg : Amantadine, 300 mg, capsule, three times a day, two weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| SOMNOLENCE | Nervous system disorders | CTCAE 4.3 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathyrn Chung MD | Oregon Health & Science Universtiy | 503 721 - 1091 | chungka@ohsu.edu |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D020820 | Dyskinesias |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D000547 | Amantadine |
| D000077236 | Topiramate |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
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| Topiramate | Drug | 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 | Drug | sugar pill, capsule, three times a day, 2 weeks |
|
| Measured every 1/2 hour for a levodopa dose cycle (starting 1 hour prior to infusion and ending 4 hours post 2-hour infusion) |
| 11391748 | Background | 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. |
| 10348468 | Background | 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. |
| 16154788 | Background | 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. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| MoCA total | The MoCA is a short cognitive screening test designed to assist health care professionals for the detection of mild cognitive impairment. The MoCA assesses cognitive function across a variety of domains. The MoCA is scored on a 0 to 30 scale, with lower numbers indicating more cognitive impairment. A point is added to the MoCA if the subject's education high school or less (12 years or less education). Scores ranging from 26 - 30 are normal, 18 - 26 mild impairment, 10 - 17 moderate impairment, and less than 10 severe cognitive impairment. | Mean | Standard Deviation | units on a scale |
|
| UPDRS (Part III) Total Score | This is the motor subsection of the UPDRS and is a commonly used tool to rate the symptoms of Parkinson's disease. Each item on the scale is rated from 0 (normal) to 4 (Can barely perform the task) several motor areas including speech, facial expression, tremor, rigidity, hand movements, agility, posture, and gait. Total score ranges from 0 to 108 with higher values on this scale represent a more severe stage of the disease. | Mean | Standard Deviation | units on a scale |
|
| mAIMS | Modified Abnormal Involuntary Movment Rating Scale (mAIMS) is a commonly utilized scale that is completed by an observer who judges the severity of dyskinesia 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 severe dyskinesia. | Mean | Standard Deviation | units on a scale |
|
| OG002 | Sugar Pill | Sugar Pill : sugar pill, capsule, three times a day, 2 weeks |
|
|
| 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. | Posted | Mean | Standard Deviation | Units on a Scale * Hours | Measured every 1/2 hour for a levodopa dose cycle (starting 1 hour prior to infusion and ending 4 hours post 2-hour infusion) |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| EG001 | Amantadine Plus Topiramate | 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 | 0 | 3 | 2 | 3 |
| EG002 | Sugar Pill | Sugar Pill : sugar pill, capsule, three times a day, 2 weeks | 0 | 3 | 3 | 3 |
| HALLUCINATIONS | Psychiatric disorders | CTCAE 4.3 | Non-systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | CTCAE 4.3 | Non-systematic Assessment |
|
| FATIGUE | General disorders | CTCAE 4.3 | Non-systematic Assessment |
|
| FLU LIKE SYMPTOMS | General disorders | CTCAE 4.3 | Non-systematic Assessment |
|
| PARESTHESIA | Nervous system disorders | CTCAE 4.3 | Non-systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D005632 | Fructose |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D002241 | Carbohydrates |
| D007661 | Ketoses |