Validation of Dyskinesia Rating Scales
Information source: Rush University Medical Center
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Parkinson's Disease
Intervention: Amantadine (Drug); Placebo (Drug)
Phase: Phase 4
Sponsored by: Rush University Medical Center
Official(s) and/or principal investigator(s):
Christopher G Goetz, MD, Principal Investigator, Affiliation: Rush University Medical Center
Glenn T Stebbins, PhD, Principal Investigator, Affiliation: Rush University Medical Center
Christopher G Goetz, MD, Phone: 312-942-8016, Email: email@example.com
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 60 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.
Official title: Validation of Dyskinesia Rating Scales
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary outcome: 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).
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.
Change score differences between week 4 and 8 to measure stability of scales over two visits on stable doses of amantadine or placebo
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)
Correlations among the scales
Correlations between scale values and Clinical Global Impressions-Severity (CGI-s) and correlations between scale changes and Clinical Global Impression of Change (CGI-c)
Safety monitoring will be operative throughout the study
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
Minimum age: 30 Years.
Maximum age: 90 Years.
1. Parkinson's disease patient, defined by UK Brain Bank criteria
2. Current age between 30-90
3. Clinically pertinent dyskinesias defined by CGI-s 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
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
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
Locations and Contacts
Christopher G Goetz, MD, Phone: 312-942-8016, Email: firstname.lastname@example.org
Universitatsklinik fur Neurologie, Innsbruck 6020, Austria; Recruiting
Werner Poewe, MD, Phone: +4351250423850, Email: email@example.com
Werner Poewe, MD, Principal Investigator
Centre d'investigation Clinique, CHU de Toulouse, Toulouse Cedex 9 31059, France; Recruiting
Olivier Rascol, MD, Phone: 05 61 77 91 03, Email: firstname.lastname@example.org
Olivier Rascol, MD, Principal Investigator
University of Alabama-Birmingham (UAB), Birmingham, Alabama 35043, United States; Recruiting
Rachel Clark, RN, Phone: 205-996-2647
Anthony Nicholas, MD, Principal Investigator
University of South Florida, Tampa, Florida 33606, United States; Recruiting
Holly Delgado, RN, BSN, Phone: 813-844-4455, Email: email@example.com
Robert Hauser, MD, Principal Investigator
Rush University Medical Center, Chicago, Illinois 60612, United States; Recruiting
Lucia M Blasucci, RN, Phone: 312-563-2900, Ext: Press 4, Email: Lucia_M_Blasucci@rush.edu
Christopher G Goetz, MD, Principal Investigator
Duke University, Durham, North Carolina 27705, United States; Recruiting
Lisa Gauger, Phone: 919-668-1538, Email: firstname.lastname@example.org
Mark Stacy, MD, Principal Investigator
Toronto Western Hospital (Movement Disorder Center), Toronto, Ontario M5T2S8, Canada; Recruiting
Francis Baraquio, Phone: 416-603-5800, Ext: 2664, Email: email@example.com
Janis M Miyasaki, MD, Principal Investigator
Oregon Health & Science University (OHSU), Portland, Oregon 97239-9059, United States; Recruiting
Rebecca Conroy, Phone: 503-494-9531, Email: firstname.lastname@example.org
Kathy Chung, MD, Principal Investigator
Jay Nutt, MD, Sub-Investigator
Starting date: January 2010
Last updated: July 20, 2011