Effect of Intravenous Amantadine on Gait Freezing in Parkinson's Disease

Study Overview
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Brief Summary
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A double-blinded randomized placebo-controlled trial of intravenous amantadine on gait freezing refractory to oral anti-parkinsonian medications in patients with Parkinson's disease. administration of IV amantadine or normal saline for 5 days, 2 times a day while keeping current oral anti-parkinsonian medications unchanged follow-up after administration of IV amantadine for 4 weeks allocation ratio of amantadine:normal saline is 2:1

Detailed Description
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Intravenous amantadine is known to be effective for parkinsonian motor symptoms abruptly aggravated and for disabling motor symptoms from severe motor fluctuation and dyskinesia in patients with Parkinson's disease. The study investigators experienced several open label cases who were benefit from intravenous amantadine in their parkinsonian motor symptoms and freezing of gait as well. In addition, there is a pilot open label trial in parkinsonian patients with refractory freezing of gait which showed marked benefit in patients with Parkinson's disease, but not in patients with parkinson-plus syndromes. This study was aimed to evaluate the efficacy of intravenous amantadine in both levodopa-unresponsive freezing of gait and disabling off state freezing of gait in patients with Parkinson's disease.

Official Title
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Randomized Double-blind Placebo-controlled Trial of Intravenous Amantadine on Gait Freezing in Patients With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: amantadine sulfate
* Drug: 0.9% sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the diagnosis of Parkinson's disease according to the United Kingdom Parkinson's Disease Brain Bank criteria presence of freezing of gait and the scores of Freezing of Gait Questionnaire 7 or more having been treated with oral dopamine replacement therapy for 6 months or more score of Korean version of mini-mental status examination is 20 or more Exclusion Criteria: presence of significant cognitive dysfunction, behavioral or psychiatric disorders presence of severe cardiac disease presence of renal failure, seizure, peptic ulcer disease, liver disease, pheochromocytoma, chronic exhaustive disease, or malignancy participation to other clinical trial within 4 weeks pregnancy or lactating women hypersensitivity to study drugs history of intoxication to heavy metals

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: amantadine<br>administration of intravenous amantadine sulfate 200mg/500ml/bottle 1 bottle infusion over 3 hours, twice a day for consecutive 5 days | Drug: amantadine sulfate<br>* infusion of amantadine sulfate 100mg/500ml/bottle over 3 hours twice a day<br>* Other names: PK-merz;|
| Placebo Comparator: placebo<br>administration of 0.9% sodium chloride 500ml/bottle 1 bottle infusion over 3 hours twice a day for consecutive 5 days | Drug: 0.9% sodium chloride<br>* infusion of normal saline 500ml/bottle over 3 hours twice a day<br>* Other names: normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in scores on Freezing of Gait Questionnaire |  | after completion of 5-day schedule of IV amantadine treatment compared with baseline status | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in scores on Freezing of Gait Questionnaire |  | after 4-weeks of follow-up compared with baseline status | 
| changes of scores on the Unified Parkinson's disease Rating Scale Part III |  | after completion of IV amantadine treatment compared with baseline status | 
| changes of scores on the Unified Parkinson Disease Rating Scale Part III |  | after 4- weeks of follow-up compared with baseline status |