Parkinson's Disease
Conditions
Keywords
donepezil, parkinson's disease, balance, cholinesterase inhibitor
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.
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.
Interventions
DRUGDonepezil
Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.
DRUGPlacebo
Use 1 capsule (5 mg) once per day for first 21 days than 10mg qday for 21 days.
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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.
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | Total |
|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 6 |
| Mini-Mental Status Exam (MMSE) | 29.2 units on a scale STANDARD_DEVIATION 0.4 |
| Parkinson's Disease Duration (years) | 10.5 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
| Trials B-A | 59 seconds STANDARD_DEVIATION 32 |
| Unified Parkinson's Disease Rating Scale - Motor Section | 24 units on a scale STANDARD_DEVIATION 7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 16 |
| other Total, other adverse events | 6 / 18 | 1 / 16 |
| serious Total, serious adverse events | 0 / 18 | 0 / 16 |
Outcome results
Primary
Sensory Organization Test - Composite Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Sensory Organization Test - Composite Score | 7.7 score on a scale | Standard Deviation 21.6 |
| Placebo | Sensory Organization Test - Composite Score | 0.6 score on a scale | Standard Deviation 8.9 |
Primary
Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform).
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform). | 6.52 units on a scale | Standard Error 2.99 |
| Placebo | Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform). | -0.89 units on a scale | Standard Error 2.82 |
Secondary
Trails B - A
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Trails B - A | 9.4 seconds | Standard Deviation 95.6 |
| Placebo | Trails B - A | 1.4 seconds | Standard Deviation 39.9 |