Parkinson's DiseasePhase 4NCT01071395
Validation of Dyskinesia Rating Scales
A Phase 4 study testing Amantadine in people with Parkinson's Disease, run by Rush University Medical Center at 8 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 90 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Amantadine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 8 sitesin 4 countries
- Study dates
- Jan 2010to Jun 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States5 sites
University of Alabama-Birmingham (UAB)
Birmingham, Alabama, 35043
Rush University Medical Center
Chicago, Illinois, 60612
Duke University
Durham, North Carolina, 27705
Oregon Health & Science University (OHSU)
Portland, Oregon, 97239-9059
University of South Florida
Tampa, Florida, 33606
Canada1 site
Toronto Western Hospital (Movement Disorder Center)
Toronto, Ontario, M5T2S8
About this study
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.
Read the 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.
- Conditions
- Parkinson's Disease
- Being tested
- Amantadine, Placebo
- Keywords
- Parkinson's disease, Dyskinesia, Dyskinesia Rating Scales, Amantadine, Placebo
- Medical subject headings
- Parkinson Disease, Dyskinesias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmantadineDrug
Also called Symmetrel
Amantadine hydrochloride 300mg daily in three divided doses
PlaceboDrug
Also called sugar pill
Sugar pill given 3 times daily
| Study group | Role | What they receive |
|---|---|---|
| Amantadine | Experimental | Amantadine 100mg tab BID or TID for duration of study Receives: Drug: Amantadine |
| Placebo | Placebo comparator | Placebo one tab BID or TID for duration of study Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2010 (estimated)
- Study startJan 2010
- Primary completionApr 2012
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Principal investigator, Christopher G. Goetz, MD, Rush University Medical Center
- Investigators
- Christopher G Goetz, MD, Principal investigator, Rush University Medical CenterGlenn T Stebbins, PhD, Principal investigator, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01071395
- Sponsor's protocol ID
- Valid Dyskin Rating Scales
- Status last verified
- Nov 2022
- First submitted
- 17 Feb 2010
- Last updated
- 29 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of Dyskinesia Rating Scales
- ClinicalTrials.gov ID
- NCT01071395
- Acronym / sponsor ID
- Valid Dyskin Rating Scales
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, Dyskinesia, Dyskinesia Rating Scales, Amantadine, Placebo
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- Jan 2010
- Primary completion
- Apr 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 19 Feb 2010 (estimated)
- Results
- Posted 28 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amantadine | Experimental | Drug: AmantadineAmantadine 100mg tab BID or TID for duration of study |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo one tab BID or TID for duration of study |
Who may qualify
- Ages
- 30 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmantadineAlso: SymmetrelAmantadine hydrochloride 300mg daily in three divided doses | Drug | Amantadine |
| PlaceboAlso: sugar pillSugar pill given 3 times daily | Drug | Placebo |
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).
Time frame: 18 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Parkinson's Disease FoundationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher G Goetz, MD principal investigator
Rush University Medical Center
Glenn T Stebbins, PhD principal investigator
Rush University Medical Center
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amantadine in people with Parkinson's Disease, run by Rush University Medical Center at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Austria, Canada, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2022.