Topiramate as an Adjunct to Amantadine in the Treatment of Dyskinesia in Parkinson's Disease

Phase 2

Terminated

• Conditions: Idiopathic Parkinson's Disease; Drug Induced Dyskinesia
• Interventions: Drug: Placebo; Drug: Topiramate; Drug: Amantadine

• Registration Number: NCT01789047
• Lead Sponsor: Rush University Medical Center

Brief Summary

The study will involve an eighteen-week, double-blind, placebo-controlled parallel designed comparison between add-on topiramate and add-on placebo to stable treatment with amatadine in the treatment of Parkinson's disease (PD) patients who continue to have dyskinesia on amantadine.

Detailed Description

We conducted a randomized placebo controlled trial of topiramate in PD dyskinetic subjects already on amantadine but with continuing dyskinesia. Topiramate or placebo was introduced in blinded fashion with a gradual titration (topiramate 25-150 mg/d) over 6 weeks and then a maintenance period of 8 weeks. The primary outcome of interest was change from baseline to end of study in total Unified Dyskinesia Rating Scale (UDysRS) score using Intention to Treat analysis.

Study Timeline

• Study First Submitted: 2013-02-07
• Study First Submitted QC: 2013-02-07
• Study First Posted: 2013-02-11
• Study Start: 2013-03
• Primary Completion: 2016-07
• Study Completion: 2016-07
• Results First Submitted: 2017-10-12
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-25
• Last Update Submitted: 2019-03-25
• Results First Posted: 2019-04-16
• Last Update Posted: 2019-04-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. Parkinson's disease patient, defined by United Kingdom (UK) Brain Bank criteria
2. Current age between 30-90
3. Clinically pertinent dyskinesias defined by Clinical Global Impression - Severity (CGI-s) score (see attachment) > 3 (mild) established by clinician's total assessment of patient including objective observation during the screening process. *
4. Stable doses of all antiparkinsonian medications for at least 4 weeks
5. Stable treatment with at least 200 mg amantadine for at least 4 weeks.
6. Presence of a caregiver willing to participate in the study
7. 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.
8. Subjects must be free of dementia, depression and psychosis as determined by clinical examination.
9. The subject must be willing to participate in all study related activities and visits.

Exclusion criteria:

1. Any subjects with clinical evidence suggestive of an atypical or secondary form of Parkinson's Disease
2. Any subject who, in the opinion of the Principal Investigator, has a concomitant medical illness which would preclude them from being treated with amantadine,
3. Any subject who, in the opinion of the Principal Investigator, will be unable to maintain current stable dosing of their anti-parkinsonian medications for the duration of the trial,
4. Any subject with evidence for dementia, depression, or psychosis, as determined by clinical examination.
5. Any subject who has not signed informed consent, or unable or unwilling to participate in all of the study related activities.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (sugar pill)	Placebo	Placebo
Topiramate	Topiramate	Topiramate as adjunct to amantadine.
Topiramate	Amantadine	Topiramate as adjunct to amantadine.
Placebo (sugar pill)	Amantadine	Placebo

Primary Outcome Measures

Name	Time	Method
The Unified Dyskinesia Rating Scale (UDysRS)	Change from baseline to week 14 (end of study) on the Unified Dyskinesia Rating Scale	The Unified Dyskinesia Rating Scale (UDysRS) will be the primary outcome measure for this study. This choice is based on the outcome of the Validation of Dyskinesia Rating Scales study. In this study, the UDysRS was identified as the most sensitive scale to detect change in dyskinesia in an 8-week, double-blind, placebo-controlled trial of amatadine. The UDysRS utilizes rater information, patient self-report and objective measures of dyskinesia to provide assessments of impairment and disability due to dyskinesia. Score ranges are 0-108 with higher scores representing more severe impairment.

Trial Locations

Locations (5)

University of South Florida; 🇺🇸 Tampa, Florida, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Oregon Health Sciences University; 🇺🇸 Portland, Oregon, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States