Back to resultsEfficacy Study of Amantadine to Treat Gait Dysfunction and Freezing in Parkinson's Disease
Primary Purpose
Parkinson's Disease
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Amantadine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Freezing of gait, gait dysfunction
Eligibility Criteria
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
Sites / Locations
- Northwestern University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Amantadine
placebo
Arm Description
Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day
Sugar Pill
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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
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.
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)
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.
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.
Number Who Completed Medication as Randomized
Tolerability analysis as determined by the number of subjects completing each arm of the study.
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.
Full Information
NCT ID
NCT01652534
First Posted
August 15, 2011
Last Updated
October 23, 2019
Sponsor
Northwestern University
1. Study Identification
Unique Protocol Identification Number
NCT01652534
Brief Title
Efficacy Study of Amantadine to Treat Gait Dysfunction and Freezing in Parkinson's Disease
Official Title
Efficacy of Amantadine for Gait Dysfunction and Gait Freezing in Patients With Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Terminated
Why Stopped
Due to lack of recruitment
Study Start Date
June 2011 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
Subjects who meet the eligibility requirements for the study will be randomized to Amantadine versus a matching placebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Freezing of gait, gait dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Amantadine
Arm Type
Active Comparator
Arm Description
Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Sugar Pill
Intervention Type
Drug
Intervention Name(s)
Amantadine
Other Intervention Name(s)
Symmetrel
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar Pill
Intervention Description
Sugar Pill
Primary Outcome Measure Information:
Title
Timed Up and Go (TUG) - ON Usual Medication
Description
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.
Time Frame
Baseline, change at 4 weeks
Title
Timed Up and Go (TUG) - OFF Usual Medication
Description
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.
Time Frame
Baseline, change at 4 weeks
Secondary Outcome Measure Information:
Title
Modified Timed Up and Go (mTUG)
Description
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.
Time Frame
Baseline, change in 4 weeks
Title
Analysis of Motor Functioning Using the Parkinson's Home Diaries
Description
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.
Time Frame
Baseline, change in 4 weeks
Title
Freezing of Gait Questionnaire
Description
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
Time Frame
Baseline, change in 4 weeks
Title
Clinical Global Impression (CGI)
Description
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.
Time Frame
4 weeks
Title
Parkinson's Disease Questionnaire-39 (PDQ-39)
Description
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)
Time Frame
Baseline, week 4
Title
Gait Analysis Testing
Description
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.
Time Frame
Baseline, week 4, week 7, week 11
Title
Fatigue Severity Scale (FSS)
Description
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.
Time Frame
Baseline, change in 4 weeks
Title
Number Who Completed Medication as Randomized
Description
Tolerability analysis as determined by the number of subjects completing each arm of the study.
Time Frame
week 4
Title
Number of Participants With Drug Safety Reports
Description
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.
Time Frame
Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tanya Simuni, MD
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy Study of Amantadine to Treat Gait Dysfunction and Freezing in Parkinson's Disease
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