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

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01652534
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Amantadine; Drug: Placebo	Phase 3

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Amantadine for Gait Dysfunction and Gait Freezing in Patients With Parkinson's Disease
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Amantadine Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day	Drug: Amantadine; 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).; Other Names: Symmetrel
Placebo Comparator: placebo Sugar Pill	Drug: Placebo; Sugar Pill; Other Names: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. Timed Up and Go (TUG) - ON Usual Medication [Baseline, change at 4 weeks]

   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.

2. Timed Up and Go (TUG) - OFF Usual Medication [Baseline, change at 4 weeks]

   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

1. Modified Timed Up and Go (mTUG) [Baseline, change in 4 weeks]

   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.

2. Analysis of Motor Functioning Using the Parkinson's Home Diaries [Baseline, change in 4 weeks]

   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.

3. Freezing of Gait Questionnaire [Baseline, change in 4 weeks]

   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

4. Clinical Global Impression (CGI) [4 weeks]

   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.

5. Parkinson's Disease Questionnaire-39 (PDQ-39) [Baseline, week 4]

   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)

6. Gait Analysis Testing [Baseline, week 4, week 7, week 11]

   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.

7. Fatigue Severity Scale (FSS) [Baseline, change in 4 weeks]

   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.

8. Number Who Completed Medication as Randomized [week 4]

   Tolerability analysis as determined by the number of subjects completing each arm of the study.

9. Number of Participants With Drug Safety Reports [Week 4]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects with idiopathic PD as determined by UK brain bank diagnostic criteria

2. H&Y stage 2.5-3

3. Presence of freezing of gait (FOG) as determined by UPDRS Part I score > 2

4. Ability to walk for 2 minutes in the ON and OFF state

5. Stable regimen of PD medications for 30 days prior to screening

6. Ability to comply with the study procedures

7. 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.

8. Willing and able to provide informed consent.

Exclusion Criteria:

1. Presence of other co morbid conditions that can contribute to gait dysfunction (orthopedic, rheumatologic, cardiac, other)

2. Presence of freezing of gait (FOG) ONLY in medications ON state

3. Presence of freezing of gait (FOG) ONLY in medications OFF state

4. Presence of significant cognitive dysfunction as determined by Montreal Cognitive Assessment (MoCA) <20

5. Presence of clinically significant depression as determined by geriatric depression scale (GDS)- 15>5

6. Presence of clinically significant hallucinations

7. Inability to sign informed consent

8. Participation in the physical therapy aimed at management of PD for the duration of the study (PT for orthopedic issues will be allowed)

9. Contraindications for use of Amantadine ( prior history of allergic reaction, history of known renal insufficiency with Cr > 2)

10. If female, be pregnant or lactating

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Tanya Simuni, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tanya Simuni, Professor of Neurology Director, Parkinson's Disease and Movement Disorders Center, Northwestern University
• ClinicalTrials.gov Identifier: NCT01652534
• Other Study ID Numbers: M012010
• First Posted: Jul 30, 2012
• Last Update Posted: Nov 13, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Tanya Simuni, Professor of Neurology Director, Parkinson's Disease and Movement Disorders Center, Northwestern University: Freezing of gait; gait dysfunction
• Additional relevant MeSH terms: Parkinson Disease; Amantadine

Study Results

Participant Flow

Pre-assignment Detail	There was a total of 3 participants enrolled into the study. All 3 participants were randomized to receive either Amantadine or Placebo and crossed over after a washout period.

Arm/Group Title	Amantadine, Then Placebo	Placebo, Then Amantadine
Arm/Group Description	Participants first received Amantadine 100 mg tablet orally once a day for one week, then two tablets orally twice a day for one week. After a washout period of 3 weeks, they then placebo tablet (matching Amantadine 100mg tablet) orally for 4 weeks.	Participants first received Placebo tablet (matching Amantadine 100 mg tablet) orally once a day for one week, then Amantadine placebo two tablets orally twice a day for one week. After a washout period of 4 weeks, then they received Amantadine 100mg tablet orally for 4 weeks.
Period Title: Overall Study
STARTED	2	1
COMPLETED	1	1
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Amantadine Crossover to Placebo	Placebo Crossover to Amantadine	Total
Arm/Group Description	For first 4 weeks of study Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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). Crossover to Placebo (sugar pill) at week 7	For first 4 weeks of study, Placebo (sugar pill) Crossover to Amantadine at week 7 Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	2 100%	1 100%	3 100%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	2 100%	1 100%	3 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	1 100%	3 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

participants who could complete the task. Note: for the 2 participants who were tested while on placebo, one did not complete baseline, and one did not complete week 4, so a change could not be computed.

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	3	1
Baseline	16.7	17.4
Change at 4 weeks	0.04

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

participants who could complete the task.

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	2	2
Baseline	23	19.5
Change at 4 weeks	-3.5	8.6

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

participants who completed task

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	1	1
Baseline - ON	14 (0)	16 (0)
change in 4 weeks - ON	1 (0)	-1 (0)
Baseline - OFF	16 (0)	20 (0)
change in 4 weeks - OFF	2 (0)	1 (0)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

patients who report being ON and OFF medication and experience dyskinesia under either condition at baseline and after 4 weeks of either Amantadine or Placebo. NOTE: only one patient reported both dyskinesia at baseline and 4 weeks and only under the placebo condition. Others did not report any OFF time, so the difference could not be calculated.

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	1	1
Baseline	90 (0)	150 (0)
Change at 4 weeks	450 (0)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants who completed questionnaire

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	3	2
Baseline	10	15
Change at 4 weeks	-2	1

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

number completing study up to assessment

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	3	2
Median (Full Range) [score on a scale]	2	4.5

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants completing questionnaire

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	2	0
Baseline	38

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

No data was collected from the portable devices that were used.

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	0	0

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants who completed questionnaire

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	2	2
Baseline	27	26
change in 4 weeks	1.5	-5

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

participants who completed study to time of assessment

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	3	2
Count of Participants [Participants]	3 150%	2 200%

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	Amantadine 100mg daily, for a week, if it is tolerated Amantadine will increase to 1 tab twice a day Amantadine: 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).	Sugar Pill Placebo: Sugar Pill
Measure Participants	3	2
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	Amantadine		Placebo
Arm/Group Description	Participants during Amantadine 100 mg tablet orally once a day for one week, then two tablets orally twice a day for one week.		Participants during Placebo tablet (matching Amantadine 100 mg tablet)
All Cause Mortality
	Amantadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Serious Adverse Events
	Amantadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Amantadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.