Topiramate as an Adjunct to Amantadine in the Treatment of Dyskinesia in Parkinson's Disease (TOP-DYSK)

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.

Study Overview

• Status: Terminated
• Conditions: Idiopathic Parkinson's Disease; Drug Induced Dyskinesia
• Intervention / Treatment: Drug: Placebo; Drug: Topiramate; Drug: 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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University Of Alabama
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health Sciences University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Topiramate; Topiramate as adjunct to amantadine.	Drug: Topiramate; Topiramate as adjunct to amantadine; Other Names: Topamax; Drug: Amantadine; Existing treatment for all participants; Other Names: Symmetrel
Placebo Comparator: Placebo (sugar pill); Placebo	Drug: Placebo; Placebo control; Other Names: sugar pill; Drug: Amantadine; Existing treatment for all participants; Other Names: Symmetrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Unified Dyskinesia Rating Scale (UDysRS)	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.	Change from baseline to week 14 (end of study) on the Unified Dyskinesia Rating Scale

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression - Change Score	The Clinical Global Impression - Change score is an ordinal measure of change with a range of 0 (not assessed) to 7 (very much worse). A score of 4 is associated with "no change".	Assessed at Week 10 and 14 by blinded treating physician and subject
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	This is a 4-part scale that rates both non-motor and motor (including dyskinesia) aspects of Parkinson's disease. Parts of the scales will be completed by the blinded treating physician while assessing the subject and other parts will be self-completed by the subject	Assessed at baseline, week 6, week 10 and week 14
Hoehn & Yahr Staging	Hoehn & Yahr staging of Parkinson's disease is completed by the blinded treating physician assessing the subject	Assessment completed at baseline, week 6, week 10 and week 14

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Christopher G Goetz, MD, Rush University Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: February 7, 2013
• First Submitted That Met QC Criteria: February 7, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: dyskinesia; Parkinson's disease; Indonesia; amantadine
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Drug-Related Side Effects and Adverse Reactions; Poisoning; Neurotoxicity Syndromes; Parkinson Disease; Dyskinesias; Dyskinesia, Drug-Induced; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agents; Anticonvulsants; Antiparkinson Agents; Anti-Dyskinesia Agents; Topiramate; Amantadine
• Other Study ID Numbers: TOP-DYSK