Parkinson's Disease
Conditions
Keywords
parkinsons disease, falling
Brief summary
The purpose of this study is to find out if a medication that increases levels of a brain chemical called acetylcholine will improve balance and reduce falls in patients with parkinson's disease who have the problem of very poor balance and are frequently falling or nearly falling on a daily basis. Donepezil, a drug approved for the treatment of Alzheimer's dementia, will reduce falls in subjects with Parkinson's disease and balance impairment.
Detailed description
This trial is a double-blinded cross-over design comparing donepezil with placebo in 40 subjects with idiopathic Parkinson's disease who report frequent falls or near falls (\>2/week). The purpose of this study is to find out if a medication that increases levels of a brain chemical called acetylcholine will improve balance and reduce falls in patients with parkinson's disease who have the problem of very poor balance and are frequently falling or nearly falling on a daily basis. Donepezil, a drug approved for the treatment of Alzheimer's dementia, will reduce falls in subjects with Parkinson's disease and balance impairment.
Interventions
DRUGDonepezil
donepezil, 5 mg, capsule, once a day, 3 weeks
sugar pill, one capsule, once a day, 3 weeks
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age over 21 * Diagnosis of Parkinson's disease * Treated with dopaminergic medication for at least 1 year
Exclusion criteria
* Must be ambulatory (can use walker or cane) * No obvious remediable cause of falls * Falls are on basis of non-CNS etiologies (cardiogenic, orthopedic, peripheral neuropathy, etc) * Dementia present (MMSE \< 25) * Not taking cholinergic or anticholinergic medications 10 days prior to screening visit * No Warfarin use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fall Frequency Per Day | 6 weeks | The primary outcomes were fall frequency determined using daily event recording by the subjects onto postcards which accumulated data for six weeks per phase. Falls were defined as landing on the floor. Fall frequency is the number of reported falls divided by the number of days reported. Postcards were mailed back to the investigator weekly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Near Falls Per Day | 6 weeks | The secondary outcome was near fall frequency determined using daily event recording by the subjects onto postcards which accumulated data for six weeks per phase. Near falls were defined as a fall that did not land on the floor (for example grabbing a handrail or a table). Near fall frequency is the number of reported near falls divided by the number of days reported. Postcards were mailed back to the investigator weekly. |
Participant flow
Recruitment details
Adult subjects were those diagnosed with probable idiopathic PD, defined as manifesting two of three cardinal features (tremor, rigidity, bradykinesia), without any other historical or physical signs to suggest another diagnosis, and were recruited from the Oregon Health and Science University (OHSU) Movement Disorders clinic.
Pre-assignment details
This is a cross-over treatment trial. Each drug phase, donepezil or identical placebo, lasted 6 weeks, with a three week washout period in between. In each drug phase, subjects were instructed to take one tablet (mg of donepezil or placebo) for three weeks and to increase to two tablets (10 mg) for the remaining three weeks.
Participants by arm
| Arm | Count |
|---|---|
| Donepezil (6 Weeks), Washout (3 Weeks), Placebo (6 Weeks) Donepezil 5 mg qam weeks 1-3, 10 mg qam weeks 3-6 then Nothing weeks 7-9 then Placebo (sugar pill) 5 mg qam weeks 10-13, 10 mg qam weeks 14-16 | 11 |
| Placebo (6 Weeks), Washout (3 Weeks), Placebo (6 Weeks) Placebo (sugar pill) 5 mg qam weeks 1-3, 10 mg qam weeks 3-6 then Nothing weeks 7-9 then Donepezil 5 mg qam weeks 10-13, 10 mg qam weeks 14-16 | 12 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (6 Weeks) | Adverse Event | 2 | 1 |
| Second Intervention (6 Weeks) | Adverse Event | 0 | 1 |
| Second Intervention (6 Weeks) | Withdrawal by Subject | 1 | 0 |
| Washout | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo (6 Weeks), Washout (3 Weeks), Placebo (6 Weeks) | Donepezil (6 Weeks), Washout (3 Weeks), Placebo (6 Weeks) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 4 Participants | 10 Participants |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 11.5 | 71.5 years STANDARD_DEVIATION 10.2 | 68.4 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment United States | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Fall Frequency Per Day
The primary outcomes were fall frequency determined using daily event recording by the subjects onto postcards which accumulated data for six weeks per phase. Falls were defined as landing on the floor. Fall frequency is the number of reported falls divided by the number of days reported. Postcards were mailed back to the investigator weekly.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Fall Frequency Per Day | 0.13 Number Falls/Day | Standard Error 0.13 |
| Placebo | Fall Frequency Per Day | 0.25 Number Falls/Day | Standard Error 0.34 |
Comparison: Means and standard deviations were calculated to describe the subject baseline characteristics. Paired t-tests evaluated the difference between baseline and end of treatment frequency of falls. Changes post-treatment from baseline in secondary measures were also compared between the donepezil and placebo phases with paired t-tests or Wilcoxon signed rank tests when data was nonparametric. SPSS was used for the analysis.p-value: 0.049t-test, 2 sided
Secondary
Frequency of Near Falls Per Day
The secondary outcome was near fall frequency determined using daily event recording by the subjects onto postcards which accumulated data for six weeks per phase. Near falls were defined as a fall that did not land on the floor (for example grabbing a handrail or a table). Near fall frequency is the number of reported near falls divided by the number of days reported. Postcards were mailed back to the investigator weekly.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Frequency of Near Falls Per Day | 2.50 Number Near Falls/Day | Standard Error 4.1 |
| Placebo | Frequency of Near Falls Per Day | 2.04 Number Near Falls/Day | Standard Error 2.08 |
Comparison: Means and standard deviations were calculated to describe the subject baseline characteristics. Paired t-tests evaluated the difference between baseline and end of treatment frequency of falls. Changes post-treatment from baseline in secondary measures were also compared between the donepezil and placebo phases with paired t-tests or Wilcoxon signed rank tests when data was nonparametric. SPSS was used for the analysis.p-value: 0.27t-test, 2 sided