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

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

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

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: amantadine sulfate; Drug: 0.9% sodium chloride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Boramae Hospital
  • Seoul, Korea, Republic of
    • Hanyang University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: amantadine; administration of intravenous amantadine sulfate 200mg/500ml/bottle 1 bottle infusion over 3 hours, twice a day for consecutive 5 days	Drug: amantadine sulfate; infusion of amantadine sulfate 100mg/500ml/bottle over 3 hours twice a day; Other Names: PK-merz
Placebo Comparator: placebo; 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; infusion of normal saline 500ml/bottle over 3 hours twice a day; Other Names: normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Jee-Young Lee
• Collaborators: Samsung Medical Center; Seoul National University Bundang Hospital; Hanyang University; Seoul National University Boramae Hospital
• Investigators: Principal Investigator: Jinwhan Cho, M.D.,Ph.D., Department of Neurology, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: March 10, 2011
• First Posted (Estimate): March 14, 2011

Study Record Updates

• Last Update Posted (Estimate): August 9, 2012
• Last Update Submitted That Met QC Criteria: August 8, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; 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; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: SB11F001