The Effect of Donepezil on Gait and Balance in Parkinson's Disease

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01521117
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

This study involves Parkinson's disease (PD). Symptoms include slow movement, tremor, and muscle rigidity. Current medications for the treatment of PD do not improve gait and balance difficulties in individuals with PD. Donepezil (study drug) has been found to reduce falls in individuals with PD. The mechanism in which this reduction of falls occurs is unclear. The investigators study will look at what aspects of gait and balance are improved by the study drug. The study drug is not approved to treat PD in the United States or other countries because we do not know enough about it.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Donepezil; Drug: Placebo	Phase 4

Detailed Description

Parkinson's disease (PD) is a common neuro-degenerative disease affecting about 2% of the adult population in the United States over the age of 65. Some of the most disabling symptoms of Parkinson's disease are balance and gait dysfunction, leading to falls. These symptoms do not respond to current dopamine directed therapies. Evidence from both pathologic studies and advanced imaging has demonstrated that a cholinergic deficiency in the thalamus and basal ganglia is found in individuals with PD who fall compared to non-fallers. The central acting acetylcholine esterase inhibitor, donepezil, has been demonstrated to decrease falls in individuals with PD. The mechanism by which falls decreased is unknown. Our open label pilot data indicates that donepezil can improve quantitative measures of balance in individuals with PD. Suggesting that improvements in balance in the mechanism by which donepezil reduces falls. Our goal is to determine whether donepezil will:

• Improve quantitative measures of balance in subjects with Parkinson's disease compared to placebo.

• Improve quantitative measures of gait in subjects with Parkinson's disease compared to placebo.

• Improve cognitive measures in non-demented subjects with Parkinson's disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo Controlled, Crossover Study to Evaluate the Effect of Donepezil on Gait and Balance in Parkinson's Disease
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Donepezil, Then Placebo Donepezil 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6. After a washout period of 4 weeks, placebo 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6.	Drug: Donepezil; Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.; Other Names: Aricept ; Drug: Placebo; Use 1 capsule (5 mg) once per day for first 21 days than 10mg qday for 21 days.; Other Names: Sugar Pill
Experimental: Placebo, Then Donepezil Placebo 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6. After a washout period of 4 weeks, donepezil 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6.	Drug: Donepezil; Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.; Other Names: Aricept ; Drug: Placebo; Use 1 capsule (5 mg) once per day for first 21 days than 10mg qday for 21 days.; Other Names: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. Sensory Organization Test - Composite Score [Change from Day 1 of each treatment phase to Day 42 of each treatment phase]

   Balance was measured using the Sensory Organization test (SOT) on the NeuroCom Balance Master Clinical Research System platform (Neurocom International, Inc), which tests sway in 6 conditions, eyes open, eyes closed, and a moving visual surround first with a stable platform then with a moving platform. Center of Pressure (CoP) was calculated from the recordings. Forces and moments were recorded at 100Hz sampling frequency. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability).

2. Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform). [Change from Day 1 of each treatment phase to Day 42 of each treatment phase]

   Condition 4 of the Sensory Organization Test. The participants eyes are open as the surround moves and the platform remains stable. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability).

Secondary Outcome Measures

1. Trails B - A [Change from Day 1 of each treatment phase to Day 42 of each treatment phase]

   The Trail Making Test (TMT) consists of two parts (A & B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test provides information about visual search speed, scanning, speed of processing, and executive functioning. Part A measures processing speed and part B measures executive functioning. The TMT is time to complete each part of the test in seconds. Higher scores indicate greater impairment. Subtracting part A from part B (Trails B-A) is theorized to reduce the influence of the working memory and visuo-spatial demands and, therefore, provides a relatively pure indicator of executive function. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Idiopathic Parkinson's disease, defined by the UK Brain Bank criteria, with a Hoehn and Yahr score of 2 to 4

• Treated with levodopa for at least a year and on a stable antiparkinsonian regimen for at least one month

• Abnormal computerized dynamic posturography (CDP) on screening defined as a composite score below 65 (range 1-100)

Exclusion Criteria:

• Dementia defined by MMSE less than 27

• Other medical conditions other than PD affecting balance or gait as determined by the investigators

• Unable to stand unassisted for 30 minutes

• Current use of an acetylcholinesterase inhibitors or drugs with known anticholinergic properties

• Medical or psychiatric co-morbidities that may interfere with compliance or might place subject in danger as determined by the investigators

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parkinson's Center of Oregon - Oregon Health and Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Oregon Health and Science University

Investigators

• Principal Investigator: Seth Kareus, MD, Movement Disorders Program - Parkinson's Center of Oregon - Oregon Health and Science University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amie Hiller, MD, Principal Investigator, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01521117
• Other Study ID Numbers: OHSU-7363
• First Posted: Jan 30, 2012
• Last Update Posted: Oct 5, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Amie Hiller, MD, Principal Investigator, Oregon Health and Science University: donepezil; parkinson's disease; balance; cholinesterase inhibitor
• Additional relevant MeSH terms: Parkinson Disease; Donepezil

Study Results

Participant Flow

Recruitment Details

Participants were recruited through a large university movement disorders clinic in the Northwest. Inclusion criteria were idiopathic PD, treated with levodopa for at least a year, on a stable antiparkinson regiment for at least one month, abnormal dynamic posturography. Exclusion criteria: dementia (MMSE < 27), another medical condition affecting gait, unable to stand unassisted for 30 minutes, taking a cholinesterase inhibitor or anticholinergic medication.

Arm/Group Title	Donepezil, Then Placebo	Placebo, Then Donepezil
Arm/Group Description	Donepezil: Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days. After a washout of 4 weeks, Placebo: Use 1 capsule (5 mg) once per day for first 21 days 10mg qday for 21 days.	Placebo: Use 1 capsule (5 mg) once per day for first 21 days 10mg qday for 21 days. After a washout of 4 weeks, Donepezil: Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.
Period Title: First Intervention (6 Weeks)
STARTED	10	11
COMPLETED	5	8
NOT COMPLETED	5	3
Period Title: First Intervention (6 Weeks)
STARTED	5	8
COMPLETED	5	8
NOT COMPLETED	0	0
Period Title: First Intervention (6 Weeks)
STARTED	5	8
COMPLETED	5	5
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Total
Arm/Group Description	Total of all study completers.
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70 (6)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Region of Enrollment (participants) [Number]
United States	10 100%
Unified Parkinson's Disease Rating Scale - Motor Section (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	24 (7)
Parkinson's Disease Duration (years) (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.5 (8)
Mini-Mental Status Exam (MMSE) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	29.2 (0.4)
Trials B-A (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	59 (32)

Outcome Measures

1. Primary Outcome

Title	Sensory Organization Test - Composite Score
Description	Balance was measured using the Sensory Organization test (SOT) on the NeuroCom Balance Master Clinical Research System platform (Neurocom International, Inc), which tests sway in 6 conditions, eyes open, eyes closed, and a moving visual surround first with a stable platform then with a moving platform. Center of Pressure (CoP) was calculated from the recordings. Forces and moments were recorded at 100Hz sampling frequency. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability).
Time Frame	Change from Day 1 of each treatment phase to Day 42 of each treatment phase

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	Donepezil: Use 1 capsule (5 mg) of donepezil once per day for 21 days	Placebo: Use 1 capsule (5 mg) once per day for 21 days
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	7.7 (21.6)	0.6 (8.9)

2. Primary Outcome

Title	Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform).
Description	Condition 4 of the Sensory Organization Test. The participants eyes are open as the surround moves and the platform remains stable. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability).
Time Frame	Change from Day 1 of each treatment phase to Day 42 of each treatment phase

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	Donepezil: Use 1 capsule (5 mg) of donepezil once per day for 21 days	Placebo: Use 1 capsule (5 mg) once per day for 21 days
Measure Participants	10	10
Mean (Standard Error) [units on a scale]	6.52 (2.99)	-0.89 (2.82)

3. Secondary Outcome

Title	Trails B - A
Description	The Trail Making Test (TMT) consists of two parts (A & B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test provides information about visual search speed, scanning, speed of processing, and executive functioning. Part A measures processing speed and part B measures executive functioning. The TMT is time to complete each part of the test in seconds. Higher scores indicate greater impairment. Subtracting part A from part B (Trails B-A) is theorized to reduce the influence of the working memory and visuo-spatial demands and, therefore, provides a relatively pure indicator of executive function. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase.
Time Frame	Change from Day 1 of each treatment phase to Day 42 of each treatment phase

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	Donepezil: Use 1 capsule (5 mg) of donepezil once per day for 21 days	Placebo: Use 1 capsule (5 mg) once per day for 21 days
Measure Participants	10	10
Mean (Standard Deviation) [seconds]	9.4 (95.6)	1.4 (39.9)

Adverse Events

Arm/Group Title	Donepezil		Placebo
Arm/Group Description	Donepezil: Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days in either the first or last 6 weeks of the study.		Placebo: Use 1 capsule (5 mg) once per day for first 21 days 10mg qday for 21 days in either the first or last 6 weeks of the study.
All Cause Mortality
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/16 (0%)
Serious Adverse Events
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/18 (33.3%)		1/16 (6.3%)
Gastrointestinal disorders
Gastrointestinal	4/18 (22.2%)	7	0/16 (0%)	0
General disorders
Fall	2/18 (11.1%)	2	0/16 (0%)	0
Nervous system disorders
Worsening Parkinsonism	1/18 (5.6%)	1	0/16 (0%)	0
Possible Transient ischemic attacks	0/18 (0%)	0	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.