Trial Outcomes & Findings for The Effect of Donepezil on Gait and Balance in Parkinson's Disease (NCT NCT01521117)

Last Updated: 2021-10-05

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

21 participants

Primary outcome timeframe

Change from Day 1 of each treatment phase to Day 42 of each treatment phase

Results posted on

2021-10-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Donepezil, Then Placebo 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, Then Donepezil 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.
First Intervention (6 Weeks) STARTED	10	11
First Intervention (6 Weeks) COMPLETED	5	8
First Intervention (6 Weeks) NOT COMPLETED	5	3
Washout (4 Weeks) STARTED	5	8
Washout (4 Weeks) COMPLETED	5	8
Washout (4 Weeks) NOT COMPLETED	0	0
Second Intervention (6 Weeks) STARTED	5	8
Second Intervention (6 Weeks) COMPLETED	5	5
Second Intervention (6 Weeks) NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Donepezil, Then Placebo 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, Then Donepezil 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.
First Intervention (6 Weeks) Adverse Event	5	1
First Intervention (6 Weeks) Scheduling Issues	0	2
Second Intervention (6 Weeks) Adverse Event	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total n=10 Participants Total of all study completers.
Age, Continuous	70 years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants
Unified Parkinson's Disease Rating Scale - Motor Section	24 units on a scale STANDARD_DEVIATION 7 • n=5 Participants
Parkinson's Disease Duration (years)	10.5 years STANDARD_DEVIATION 8 • n=5 Participants
Mini-Mental Status Exam (MMSE)	29.2 units on a scale STANDARD_DEVIATION 0.4 • n=5 Participants
Trials B-A	59 seconds STANDARD_DEVIATION 32 • n=5 Participants

PRIMARY outcome

Timeframe: Change from Day 1 of each treatment phase to Day 42 of each treatment phase

Outcome measures

Outcome measures
Measure	Donepezil n=10 Participants Donepezil: Use 1 capsule (5 mg) of donepezil once per day for 21 days	Placebo n=10 Participants Placebo: Use 1 capsule (5 mg) once per day for 21 days
Sensory Organization Test - Composite Score	7.7 score on a scale Standard Deviation 21.6	0.6 score on a scale Standard Deviation 8.9

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Donepezil n=10 Participants Donepezil: Use 1 capsule (5 mg) of donepezil once per day for 21 days	Placebo n=10 Participants Placebo: Use 1 capsule (5 mg) once per day for 21 days
Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform).	6.52 units on a scale Standard Error 2.99	-0.89 units on a scale Standard Error 2.82

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Donepezil n=10 Participants Donepezil: Use 1 capsule (5 mg) of donepezil once per day for 21 days	Placebo n=10 Participants Placebo: Use 1 capsule (5 mg) once per day for 21 days
Trails B - A	9.4 seconds Standard Deviation 95.6	1.4 seconds Standard Deviation 39.9

Adverse Events

Donepezil

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Donepezil n=18 participants at risk 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 n=16 participants at risk 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.
Gastrointestinal disorders Gastrointestinal	22.2% 4/18 • Number of events 7	0.00% 0/16
Nervous system disorders Worsening Parkinsonism	5.6% 1/18 • Number of events 1	0.00% 0/16
Nervous system disorders Possible Transient ischemic attacks	0.00% 0/18	6.2% 1/16 • Number of events 1
General disorders Fall	11.1% 2/18 • Number of events 2	0.00% 0/16

Additional Information

Amie Hiller, MD

Oregon Health & Science University

Phone: 503 721 1091

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place