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 ]
  

• 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 ]
  

Objective/Rationale:

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.

Project Description:

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.

Anticipated Outcome:

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.