Parkinson's Disease
Conditions
Keywords
Parkinsons disease, dyskinesia, amantadine, efficacy
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.
Interventions
DRUGAmantadine 300 mg
Amantadine, 300 mg, capsule, three times a day, two weeks
DRUGTopiramate
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
DRUGSugar Pill
sugar pill, capsule, three times a day, 2 weeks
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| mAIMS | 7 units on a scale STANDARD_DEVIATION 7.2 |
| MoCA total | 27.7 units on a scale STANDARD_DEVIATION 1.3 |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
| UPDRS (Part III) Total Score | 16.0 units on a scale STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 2 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Forceplate AUC
Area under the curve for the root mean squared velocity in the anterior-posterior direction as measured by a forceplate.
Time frame: Every 1/2 hour for 8 hour levodopa cycle
Population: triple cross-over study design.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amantadine | Forceplate AUC | 10.4 (meters/second)*hours | Standard Deviation 5.6 |
| Amantadine Plus Topiramate | Forceplate AUC | 9.4 (meters/second)*hours | Standard Deviation 3.5 |
| Sugar Pill | Forceplate AUC | 19.1 (meters/second)*hours | Standard Deviation 18.8 |
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.
Time frame: Measured every 1/2 hour for a levodopa dose cycle (starting 1 hour prior to infusion and ending 4 hours post 2-hour infusion)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amantadine | Modified Abnormal Involuntary Movement Scale Area Under the Curve | 4.0 Units on a Scale * Hours | Standard Deviation 2.9 |
| Amantadine Plus Topiramate | Modified Abnormal Involuntary Movement Scale Area Under the Curve | 5.3 Units on a Scale * Hours | Standard Deviation 4.4 |
| Sugar Pill | Modified Abnormal Involuntary Movement Scale Area Under the Curve | 8.5 Units on a Scale * Hours | Standard Deviation 8.6 |