Validation of Dyskinesia Rating Scales

NCT ID: NCT01071395

Last Updated: 2022-12-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2013-06-30

Brief Summary

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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

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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.

Conditions

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Parkinson's Disease

Keywords

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Parkinson's disease Dyskinesia Dyskinesia Rating Scales Amantadine Placebo

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Amantadine

Amantadine 100mg tab BID or TID for duration of study

Group Type EXPERIMENTAL

Amantadine

Intervention Type DRUG

Amantadine hydrochloride 300mg daily in three divided doses

Placebo

Placebo one tab BID or TID for duration of study

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Sugar pill given 3 times daily

Interventions

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Amantadine

Amantadine hydrochloride 300mg daily in three divided doses

Intervention Type DRUG

Placebo

Sugar pill given 3 times daily

Intervention Type DRUG

Other Intervention Names

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Symmetrel sugar pill

Eligibility Criteria

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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.
Minimum Eligible Age

30 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role collaborator

Rush University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Christopher G. Goetz, MD

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher G Goetz, MD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Glenn T Stebbins, PhD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Locations

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University of Alabama-Birmingham (UAB)

Birmingham, Alabama, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Oregon Health & Science University (OHSU)

Portland, Oregon, United States

Site Status

Universitatsklinik fur Neurologie

Innsbruck, , Austria

Site Status

Toronto Western Hospital (Movement Disorder Center)

Toronto, Ontario, Canada

Site Status

Centre d'investigation Clinique, CHU de Toulouse

Toulouse, , France

Site Status

Countries

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United States Austria Canada France

Related Links

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http://www.pdf.org/

Parkinson's Disease Foundation

Other Identifiers

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Valid Dyskin Rating Scales

Identifier Type: -

Identifier Source: org_study_id