Efficacy Study of Amantadine to Treat Gait Dysfunction and Freezing in Parkinson's Disease

Study Overview
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Brief Summary
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The purpose of this study is to explore the efficacy of the drug Amantadine for the treatment of freezing of gait in patients with Parkinson's Disease. The investigators hypothesize that amantadine is useful for management of freezing of gait in subjects with Parkinson's Disease.

Detailed Description
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Subjects who meet the eligibility requirements for the study will be randomized to Amantadine versus a matching placebo.

Official Title
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Efficacy of Amantadine for Gait Dysfunction and Gait Freezing in Patients With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Amantadine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with idiopathic PD as determined by UK brain bank diagnostic criteria H&Y stage 2.5-3 Presence of freezing of gait (FOG) as determined by UPDRS Part I score > 2 Ability to walk for 2 minutes in the ON and OFF state Stable regimen of PD medications for 30 days prior to screening Ability to comply with the study procedures If female, be either post menopausal for at least 2 years, surgically sterilized or have undergone hysterectomy or, if of child bearing potential they must be willing to avoid pregnancy by using an adequate method of contraception as defined in Section 6.4.10 for four weeks prior to, during and four weeks after the last dose of trial medication. For the purposes of this trial, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive. Willing and able to provide informed consent. Exclusion Criteria: Presence of other co morbid conditions that can contribute to gait dysfunction (orthopedic, rheumatologic, cardiac, other) Presence of freezing of gait (FOG) ONLY in medications ON state Presence of freezing of gait (FOG) ONLY in medications OFF state Presence of significant cognitive dysfunction as determined by Montreal Cognitive Assessment (MoCA) <20 Presence of clinically significant depression as determined by geriatric depression scale (GDS)- 15>5 Presence of clinically significant hallucinations Inability to sign informed consent Participation in the physical therapy aimed at management of PD for the duration of the study (PT for orthopedic issues will be allowed) Contraindications for use of Amantadine ( prior history of allergic reaction, history of known renal insufficiency with Cr > 2) If female, be pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amantadine<br>Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day | Drug: Amantadine<br>* Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day. Amantadine will then be administered orally twice daily in the morning with breakfast and at noon with lunch (AM and NN).<br>* Other names: Symmetrel;|
| Placebo Comparator: placebo<br>Sugar Pill | Drug: Placebo<br>* Sugar Pill<br>* Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timed Up and Go (TUG) - ON Usual Medication | This is a walking assessment. The subject will begin in the seated position, stand up, walk 7 meters, turn around, and sit back down. The entire process from leaving the chair to returning to the chair will be timed. Also, the Timed Up and Go (TUG) will be done both in the ON and OFF states. | Baseline, change at 4 weeks | 
| Timed Up and Go (TUG) - OFF Usual Medication | This is a walking assessment. The subject will begin in the seated position, stand up, walk 7 meters, turn around, and sit back down. The entire process from leaving the chair to returning to the chair will be timed. Also, the Timed Up and Go (TUG) will be done both in the ON and OFF states. | Baseline, change at 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Timed Up and Go (mTUG) | The subject sits in the chair approximately 3 1/2 meters away from doorway with the door closed. Subject then stands up and walks one meter to a 40cm X 40cm box taped on the floor. Within the box the patient turns clockwise (360 degrees), then turns counterclockwise (360 degrees). Walk to open the door and walk through the doorway, turn around and return to the chair. Modified Timed Up and Go (mTUG) completed in three components including walking the course without additional tasks, carrying a tray with a cup of water, and counting backwards from 100, in both ON and OFF state. | Baseline, change in 4 weeks | 
| Analysis of Motor Functioning Using the Parkinson's Home Diaries | Subject will record motor activity as OFF, ON (mobility improved) or asleep on the diary every half hour for two days. Subjects further define ON time according to dyskinesia categories none, non-troublesome or troublesome. The home diaries are used as an evaluation measure of the intervention by assessing the change in off time and change in on time with troublesome dyskinesia. The difference in time experiencing dyskinesia while ON meds relative to the time OFF meds at baseline and at 4 weeks is compared. | Baseline, change in 4 weeks | 
| Freezing of Gait Questionnaire | A questionnaire that is used to assess the likelihood of the subject freezing in a number of different scenarios. 0=No freezing of gait to 24=severe freezing of gait | Baseline, change in 4 weeks | 
| Clinical Global Impression (CGI) | Global Improvement is the second scale in the clinical global impression (CGI). Total overall improvement is judged by whether or not, in the judgment of the assessor, the improvement is entirely due to the drug treatment. It is also a 1-7 point weighted scale, going from very much improved (1) to very much worse (7). A zero score is assigned if the score is not assessed. | 4 weeks | 
| Parkinson's Disease Questionnaire-39 (PDQ-39) | The Parkinson's Disease Questionnaire-39 (PDQ39) is a copyrighted instrument to assess symptoms of Parkinson's disease (PD) with 39 questions relating to mobility, activities of daily living, emotional well-being, social support, cognition, communication and bodily discomfort. The test asks subjects to rate each question regarding their Parkinson's disease symptoms over the past month. (range 0 to 100, lower scores reflect better quality of life) | Baseline, week 4 | 
| Gait Analysis Testing | Use of an accelerometer such as Motorola Droid and wireless acceleration sensors to record gait parameters step time, walking speed, and cadence during the timed up and go (TUG) and modified timed up and go (mTUG) components. The sensors will be attached to the subject's legs and trunk using Velcro straps. The accelerometer will be held or clipped onto the subject in order to measure his or her acceleration. This is done within clinic and during the visit time. | Baseline, week 4, week 7, week 11 | 
| Fatigue Severity Scale (FSS) | A questionnaire used to discriminate between Parkinson Disease (PD) patients with fatigue and those without fatigue. Range 9 to 63, higher scores indicate greater fatigue severity. | Baseline, change in 4 weeks | 
| Number Who Completed Medication as Randomized | Tolerability analysis as determined by the number of subjects completing each arm of the study. | week 4 | 
| Number of Participants With Drug Safety Reports | Analyzing the safety of the medication, Amantadine. Data regarding the medication will be collected from the patient on each visit including any adverse events since the last visit, frequency and severity of falls. This is done in order to determine the safety of Amantadine. | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Freezing of gait, gait dysfunction