Validation of Dyskinesia Rating Scales
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease; Dyskinesias
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Amantadine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Amantadine hydrochloride 300mg daily in three divided doses; Sugar pill given 3 times daily
Other intervention name(s): Symmetrel; sugar pill
Intervention MeSH terms: Amantadine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Parkinson's disease; Dyskinesia; Dyskinesia Rating Scales; Amantadine; Placebo