Drug Induced Dyskinesia, Idiopathic Parkinson's Disease
Conditions
Keywords
Parkinson's disease, dyskinesia, Indonesia, amantadine
Brief summary
The study will involve an eighteen-week, double-blind, placebo-controlled parallel designed comparison between add-on topiramate and add-on placebo to stable treatment with amatadine in the treatment of Parkinson's disease (PD) patients who continue to have dyskinesia on amantadine.
Detailed description
We conducted a randomized placebo controlled trial of topiramate in PD dyskinetic subjects already on amantadine but with continuing dyskinesia. Topiramate or placebo was introduced in blinded fashion with a gradual titration (topiramate 25-150 mg/d) over 6 weeks and then a maintenance period of 8 weeks. The primary outcome of interest was change from baseline to end of study in total Unified Dyskinesia Rating Scale (UDysRS) score using Intention to Treat analysis.
Interventions
DRUGTopiramate
Topiramate as adjunct to amantadine
DRUGPlacebo
Placebo control
DRUGAmantadine
Existing treatment for all participants
Sponsors
Michael J. Fox Foundation for Parkinson's Research
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Parkinson's disease patient, defined by United Kingdom (UK) Brain Bank criteria 2. Current age between 30-90 3. Clinically pertinent dyskinesias defined by Clinical Global Impression - Severity (CGI-s) score (see attachment) \> 3 (mild) established by clinician's total assessment of patient including objective observation during the screening process. \* 4. Stable doses of all antiparkinsonian medications for at least 4 weeks 5. Stable treatment with at least 200 mg amantadine for at least 4 weeks. 6. Presence of a caregiver willing to participate in the study 7. In the opinion of the enrolling investigator, the subject will be able to maintain current dosing schedule of antiparkinsonian drugs for the duration of the trial. 8. Subjects must be free of dementia, depression and psychosis as determined by clinical examination. 9. The subject must be willing to participate in all study related activities and visits.
Exclusion criteria
1. Any subjects with clinical evidence suggestive of an atypical or secondary form of Parkinson's Disease 2. Any subject who, in the opinion of the Principal Investigator, has a concomitant medical illness which would preclude them from being treated with amantadine, 3. Any subject who, in the opinion of the Principal Investigator, will be unable to maintain current stable dosing of their anti-parkinsonian medications for the duration of the trial, 4. Any subject with evidence for dementia, depression, or psychosis, as determined by clinical examination. 5. Any subject who has not signed informed consent, or unable or unwilling to participate in all of the study related activities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Unified Dyskinesia Rating Scale (UDysRS) | Change from baseline to week 14 (end of study) on the Unified Dyskinesia Rating Scale | The Unified Dyskinesia Rating Scale (UDysRS) will be the primary outcome measure for this study. This choice is based on the outcome of the Validation of Dyskinesia Rating Scales study. In this study, the UDysRS was identified as the most sensitive scale to detect change in dyskinesia in an 8-week, double-blind, placebo-controlled trial of amatadine. The UDysRS utilizes rater information, patient self-report and objective measures of dyskinesia to provide assessments of impairment and disability due to dyskinesia. Score ranges are 0-108 with higher scores representing more severe impairment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Change Score | Assessed at Week 10 and 14 by blinded treating physician and subject | The Clinical Global Impression - Change score is an ordinal measure of change with a range of 0 (not assessed) to 7 (very much worse). A score of 4 is associated with no change. |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | Assessed at baseline, week 6, week 10 and week 14 | This is a 4-part scale that rates both non-motor and motor (including dyskinesia) aspects of Parkinson's disease. Parts of the scales will be completed by the blinded treating physician while assessing the subject and other parts will be self-completed by the subject |
| Hoehn & Yahr Staging | Assessment completed at baseline, week 6, week 10 and week 14 | Hoehn & Yahr staging of Parkinson's disease is completed by the blinded treating physician assessing the subject |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Topiramate as adjunct to amantadine.
Topiramate: Topiramate as adjunct to amantadine | 21 |
| Placebo (Sugar Pill) Placebo
Placebo: Placebo control | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Topiramate | Placebo (Sugar Pill) | Total |
|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 6.9 | 63.1 years STANDARD_DEVIATION 8.9 | 62.7 years STANDARD_DEVIATION 7.4 |
| Region of Enrollment United States | 21 Participants | 21 Participants | 42 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 15 Participants | 12 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 16 / 21 | 12 / 21 |
| serious Total, serious adverse events | 2 / 21 | 0 / 21 |
Outcome results
Primary
The Unified Dyskinesia Rating Scale (UDysRS)
The Unified Dyskinesia Rating Scale (UDysRS) will be the primary outcome measure for this study. This choice is based on the outcome of the Validation of Dyskinesia Rating Scales study. In this study, the UDysRS was identified as the most sensitive scale to detect change in dyskinesia in an 8-week, double-blind, placebo-controlled trial of amatadine. The UDysRS utilizes rater information, patient self-report and objective measures of dyskinesia to provide assessments of impairment and disability due to dyskinesia. Score ranges are 0-108 with higher scores representing more severe impairment.
Time frame: Change from baseline to week 14 (end of study) on the Unified Dyskinesia Rating Scale
Population: Last Observation Carried Forward imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | The Unified Dyskinesia Rating Scale (UDysRS) | 4.00 units on a scale | Standard Deviation 11.34 |
| Placebo (Sugar Pill) | The Unified Dyskinesia Rating Scale (UDysRS) | 1.67 units on a scale | Standard Deviation 10.27 |
Other Pre-specified
Clinical Global Impression - Change Score
The Clinical Global Impression - Change score is an ordinal measure of change with a range of 0 (not assessed) to 7 (very much worse). A score of 4 is associated with no change.
Time frame: Assessed at Week 10 and 14 by blinded treating physician and subject
Other Pre-specified
Hoehn & Yahr Staging
Hoehn & Yahr staging of Parkinson's disease is completed by the blinded treating physician assessing the subject
Time frame: Assessment completed at baseline, week 6, week 10 and week 14
Other Pre-specified
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
This is a 4-part scale that rates both non-motor and motor (including dyskinesia) aspects of Parkinson's disease. Parts of the scales will be completed by the blinded treating physician while assessing the subject and other parts will be self-completed by the subject
Time frame: Assessed at baseline, week 6, week 10 and week 14