Validation of Dyskinesia Rating Scales

NCT01071395 | Completed Phase 4 Results DMC

• 1 other identifier: Valid Dyskin Rating Scales
• Study Type: interventional
• Target: 68
• Locations: 4 countries
• Sites: 8

Brief 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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Dyskinesia; Dyskinesia Rating Scales; Amantadine; Placebo

Outcome Measures

Primary Outcomes (1)

• 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).

  Analyses of primary outcome measures tested sensitivity to change in dyskinesia (time effect) as well as sensitivity to differences in treatment effect (time-by-treatment interaction). These analyses were conducted using repeated-measures ANOVA (RM-ANOVA) or nonparametric analyses (Friedman's ANOVA with follow-up Wilcoxon tests). The RM-ANOVAs tested for changes in scale scores over baseline, week 4, and week 8 visits across the entire sample (time effect), as well as differences in these changes over time between treatment groups (time-by-treatment interaction). Effect size of time to change was compared using a partial eta-square estimate of effect size. An eta-squared less than or equal to 0.01 is considered small; 0.06 is considered medium; and, 0.14 is considered large.

  18 months

Study Arms (2)

Amantadine

EXPERIMENTAL

Amantadine 100mg tab BID or TID for duration of study

Drug: Amantadine

Placebo

PLACEBO COMPARATOR

Placebo one tab BID or TID for duration of study

Drug: Placebo

Interventions

Amantadine DRUG

Amantadine hydrochloride 300mg daily in three divided doses

Also known as: Symmetrel

Amantadine

Placebo DRUG

Sugar pill given 3 times daily

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parkinson's disease patient, defined by United Kingdom Brain Bank criteria
• Current age between 30-90
• 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. \*
• Documentation of creatinine level at screening evaluation that is within the normal range for the local university laboratory.
• Stable doses of all antiparkinsonian medications for at least 4 weeks
• No treatment with amantadine for at least 3 months.
• Presence of a caregiver willing to participate in the study
• 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).
• Subjects must be able to provide written informed consent.
• If the subject received amantadine in the past, the drug was stopped for reason other than adverse events.
• 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.
• The subject must be willing to participate in all study related activities and visits.

You may not qualify if:

• Subjects who have had prior brain surgery.
• Subjects with other major illnesses that could be complicated by amantadine exposure, including glaucoma, current hallucinations, urinary retention.
• Subjects with dementia, depression and psychosis as determined by clinical examination.

Sponsors & Collaborators

• Rush University Medical Center: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (8)

University of Alabama-Birmingham (UAB)

Birmingham, Alabama, 35043, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239-9059, United States

Location

Universitatsklinik fur Neurologie

Innsbruck, 6020, Austria

Location

Toronto Western Hospital (Movement Disorder Center)

Toronto, Ontario, M5T2S8, Canada

Location

Centre d'investigation Clinique, CHU de Toulouse

Toulouse, 31059, France

Location

Related Links

• Parkinson's Disease Foundation

MeSH Terms

Conditions

Parkinson Disease; Dyskinesias

Interventions

Amantadine; Sugars

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Carbohydrates

Limitations and Caveats

Study limitations include the patient population universally derived from university centers and the short duration of the program.

Results Point of Contact

• Title: Dr. Christopher G. Goetz
• Organization: Rush University of Medical Center

cgoetz@rush.edu

312-942-8016

Study Officials

• Christopher G Goetz, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

• Glenn T Stebbins, PhD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 17, 2010
• First Posted: February 19, 2010
• Study Start: January 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: June 1, 2013
• Last Updated: December 29, 2022
• Results First Posted: May 28, 2015

Record last verified: 2022-11

Locations

US (5); AU (1); CA (1); FR (1)