Validation of Dyskinesia Rating Scales
This study will evaluate the responsiveness of a variety of available dyskinesia rating scales to treatment with amantadine or placebo in Parkinson's disease patients with dyskinesia. The study will be a parallel, double-blind, randomized trial of 68 patients treated with amantadine or placebo for 8 weeks. Pre-treatment evaluations will be performed and compared to end of study evaluations on the best treatment dose (200 or 300 mg amantadine or matching placebo) daily. Safety evaluations will be conducted.
The responsiveness of the different scales will be evaluated statistically with a mixed model in which changes in the outcome measures over time will include a fixed effect of treatment group assignment. The model will additionally account for random effects of intercepts (the scale scores at baseline) that will include both random variation (person-specific) and specific variation associated with rate of change in outcome. The investigators may include adjustments for possible confounding covariates, including baseline demographics and center. The goal of the program is to provide researchers with the best scale(s) to distinguish dyskinesia change in Parkinson's disease (PD) associated with amantadine in comparison to placebo and to establish the magnitude of effect achievable with amantadine as a comparator "gold standard" that must be met or surpassed by future anti-dyskinetic agents. Additionally, with the use of paper and pencil questionnaires, the study will investigate the impact of patient optimism and patient and rater expectation of positive effects on the dyskinesia rating outcomes.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
|Official Title:||Validation of Dyskinesia Rating Scales|
- The Investigators Will Assess Effect Size With Each Scale for Detecting Change From Baseline and Change Between Amantadine and Placebo; Allowing Assessment of Sensitivity and Specificity for Each Scale Based on Receiver Operator Characteristics (ROC). [ Time Frame: 18 months ] [ Designated as safety issue: No ]Analyses of primary outcome measures tested sensitivity to change in dyskinesia (time effect) as well as sensitivity to differences in treatment effect (time-by-treatment interaction). These analyses were conducted using repeated-measures ANOVA (RM-ANOVA) or nonparametric analyses (Friedman's ANOVA with follow-up Wilcoxon tests). The RM-ANOVAs tested for changes in scale scores over baseline, week 4, and week 8 visits across the entire sample (time effect), as well as differences in these changes over time between treatment groups (time-by-treatment interaction). Effect size of time to change was compared using a partial eta-square estimate of effect size. An eta-squared less than or equal to 0.01 is considered small; 0.06 is considered medium; and, 0.14 is considered large.
- Differences in Slope From Baseline (BL) to End of Study (Data Will Include the 4 Week Scores) Between Placebo and Amantadine to Determine Which Scales Demonstrate Sensitivity Across Time. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Change Score Differences Between Week 4 and 8 to Measure Stability of Scales Over Two Visits on Stable Doses of Amantadine or Placebo [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- If Sufficient Number Are Maintained on 200 mg/Day, Differences in Change Scores Between 200 mg/Day and 300 mg/Day Amantadine. (This Analysis Will be BL vs End of Study) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Correlations Among the Scales [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Correlations Between Scale Values and Clinical Global Impressions-Severity (CGI-s) and Correlations Between Scale Changes and Clinical Global Impression of Change (CGI-c) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Safety Monitoring Will be Operative Throughout the Study [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2010|
|Study Completion Date:||June 2013|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Amantadine 100mg tab BID or TID for duration of study
Amantadine hydrochloride 300mg daily in three divided doses
Other Name: Symmetrel
Placebo Comparator: Placebo
Placebo one tab BID or TID for duration of study
Sugar pill given 3 times daily
Other Name: sugar pill
Dyskinesias, or involuntary jerking movements, are troublesome problems for many Parkinson's disease patients. Chemical studies have led to the development of several new treatment strategies. However, because dyskinesias are cause various degrees of difficulty for patients and are often perceived by patients and caregivers differently than by doctors, the rating of dyskinesias remains a scientific challenge. This program will examine a wide gamut of available rating scales to determine which one(s) detect change during dyskinesia treatment. Establishing excellent measurement tools of dyskinesias will allow future treatments to be evaluated in a uniform and maximally effective manner.
An team of experts will test several dyskinesia scales in a group of Parkinson's disease patients with dyskinesia. Patients will be treated with either amantadine or placebo (an inactive product). The study will be "blinded" so that the raters and the patients do not know if a given patient is receiving amantadine or placebo. Amantadine is selected for this trial, because it is the only drug that has received the designation of Efficacious for dyskinesia by the Movement Disorder Society. This conclusion was based however, on small studies and no large clinical trial of this drug has been conducted in dyskinetic patients. The scales will assess dyskinesia before and after several weeks of treatment.
Relevance to Diagnosis/Treatment of Parkinson's Disease:
This study will establish a "gold standard" for rating dyskinesia in future trials of treatments in Parkinson's disease patients. It will allow physicians to know the level of change that occurs with a standard and available treatment (amantadine) and to compare that level with changes that occur with newer treatments. Patients will benefit from this new international standard, because they can compare the likelihood and magnitude of anticipated improvement from different dyskinesia treatments, whether medical or surgical.
The anticipated outcomes of this study are:
- The impact of amantadine treatment on dyskinesia will be clearly defined.
- The effect that participation in a clinical program, even if no amantadine is given ("placebo improvements") will be delineated.
- A hierarchy of numerous scales will be determined based on their absolute and relative capability to detect change during treatment.
- The best scale(s) to evaluate dyskinesia in clinical practice and research efforts will be identified.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01071395
|United States, Alabama|
|University of Alabama-Birmingham (UAB)|
|Birmingham, Alabama, United States, 35043|
|United States, Florida|
|University of South Florida|
|Tampa, Florida, United States, 33606|
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|United States, North Carolina|
|Durham, North Carolina, United States, 27705|
|United States, Oregon|
|Oregon Health & Science University (OHSU)|
|Portland, Oregon, United States, 97239-9059|
|Universitatsklinik fur Neurologie|
|Innsbruck, Austria, 6020|
|Toronto Western Hospital (Movement Disorder Center)|
|Toronto, Ontario, Canada, M5T2S8|
|Centre d'investigation Clinique, CHU de Toulouse|
|Toulouse Cedex 9, France, 31059|
|Principal Investigator:||Christopher G Goetz, MD||Rush University Medical Center|
|Principal Investigator:||Glenn T Stebbins, PhD||Rush University Medical Center|