Validation of Dyskinesia Rating Scales

This study has been completed.
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
Christopher G. Goetz, MD, Rush University Medical Center
ClinicalTrials.gov Identifier:
NCT01071395
First received: February 17, 2010
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: Amantadine
Drug: Placebo
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Rush University Medical Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 60
Study Start Date: January 2010
Study Completion Date: June 2013
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amantadine Drug: Amantadine
Amantadine hydrochloride 300mg daily in three divided doses
Other Name: Symmetrel
Placebo Comparator: Placebo Drug: Placebo
Sugar pill given 3 times daily
Other Name: sugar pill

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.
  Eligibility

Ages Eligible for Study:   30 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01071395

Locations
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
Duke University
Durham, North Carolina, United States, 27705
United States, Oregon
Oregon Health & Science University (OHSU)
Portland, Oregon, United States, 97239-9059
Austria
Universitatsklinik fur Neurologie
Innsbruck, Austria, 6020
Canada, Ontario
Toronto Western Hospital (Movement Disorder Center)
Toronto, Ontario, Canada, M5T2S8
France
Centre d'investigation Clinique, CHU de Toulouse
Toulouse Cedex 9, France, 31059
Sponsors and Collaborators
Rush University Medical Center
Michael J. Fox Foundation for Parkinson's Research
Investigators
Principal Investigator: Christopher G Goetz, MD Rush University Medical Center
Principal Investigator: Glenn T Stebbins, PhD Rush University Medical Center
  More Information

No publications provided

Responsible Party: Christopher G. Goetz, MD, MD, Rush University Medical Center
ClinicalTrials.gov Identifier: NCT01071395     History of Changes
Other Study ID Numbers: Valid Dyskin Rating Scales
Study First Received: February 17, 2010
Last Updated: May 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Rush University Medical Center:
Parkinson's disease
Dyskinesia
Dyskinesia Rating Scales
Amantadine
Placebo

Additional relevant MeSH terms:
Dyskinesias
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Parkinsonian Disorders
Signs and Symptoms
Amantadine
Analgesics
Analgesics, Non-Narcotic
Anti-Dyskinesia Agents
Anti-Infective Agents
Antiparkinson Agents
Antiviral Agents
Central Nervous System Agents
Dopamine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014