Validation of Dyskinesia Rating Scales
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease; Dyskinesias
Intervention: Amantadine; Placebo
Intervention description: Amantadine hydrochloride 300mg daily in three divided doses; Sugar pill given 3 times daily
Intervention MeSH terms: Amantadine
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 68.0
Sex: All
Minimum age: 30 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Parkinson's disease; Dyskinesia; Dyskinesia Rating Scales; Amantadine; Placebo

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Parkinson's disease patient, defined by United Kingdom Brain Bank criteria

          2. Current age between 30-90

          3. Clinically pertinent dyskinesias defined by Clinical Gl;obal Impression-severity score
             (see attachment) > 3 (mild) established by clinician's total assessment of patient
             including objective observation during the screening process. *

          4. Documentation of creatinine level at screening evaluation that is within the normal
             range for the local university laboratory.

          5. Stable doses of all antiparkinsonian medications for at least 4 weeks

          6. No treatment with amantadine for at least 3 months.

          7. Presence of a caregiver willing to participate in the study

          8. Subjects/caregivers must demonstrate the capacity to complete an accurate home diary
             based on training and evaluation during the screening period (see attached training
             rules).

          9. Subjects must be able to provide written informed consent.

         10. If the subject received amantadine in the past, the drug was stopped for reason other
             than adverse events.

         11. 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.

         12. The subject must be willing to participate in all study related activities and visits.

        Exclusion Criteria:

          1. Subjects who have had prior brain surgery.

          2. Subjects with other major illnesses that could be complicated by amantadine exposure,
             including glaucoma, current hallucinations, urinary retention.

          3. Subjects with dementia, depression and psychosis as determined by clinical
             examination.