Cognitive Impairment, Parkinson's Disease
Conditions
Keywords
Parkinson's disease
Brief summary
The purpose of this study is to determine the safety and effectiveness of a drug called atomoxetine for the treatment of cognitive impairment for Parkinson 's disease. Atomoxetine (ATM) is an approved drug currently on the market for the treatment of attention deficit. It works to increase the amount of norepinephrine (a chemical in the brain that helps keep us awake and alert) in our brain. ATM has not been approved by the Food and Drug Administration (FDA) to be used in the treatment of PD.
Interventions
DRUGAtomoxetine
The study drug target dose is ATM 80mg per day; given as a once daily dose of an 80mg capsule. Patients will titrate up to target dose by starting on ATM 40mg capsules: 1 capsule daily for 14 days. Following study visit 3 (after 2 weeks on the titration dose), patients will increase the dose of ATM to 80mg daily.
DRUGPlacebo
Sponsors
Michael J. Fox Foundation for Parkinson's Research
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of idiopathic PD according to the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria * Male or female subjects aged between 35 and 75 years, inclusive at the time of consent * Hoehn & Yahr Stage I-IV * Diagnosis of PD mild cognitive impairment (MCI), Montreal Cognitive Assessment (MoCa) score 21-25 * Stable concomitant medications for 60 days
Exclusion criteria
* Secondary parkinsonism or atypical parkinsonism, Prior Deep Brain Stimulation (DBS) or other brain surgery * PD Dementia; MoCA score \<21 * Presence of Psychosis, pregnancy, suicidal ideation on the Columbia Suicide Severity Rating Scale (C-SSRS) type 4 or 5 in past 3 months. * Current treatment with anticholinergics, monoamine oxidase (MAO) inhibitors or neuroleptics (including quetiapine) * Serious cardiac abnormalities, Narrow angle glaucoma, Pheochromocytoma, Bipolar Disorder * Liver Function Tests (LFTs) \>1.5 X upper limit of normal value
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Global Statistical Test Combined Information on Change From Baseline on a Battery of Standardized Executive Function Tests | change from baseline and 10 weeks | Patients were ranked on each outcome and ranks were summed. The mean summed-ranks were compared by treatment group by a global statistical test (GST). Higher scores indicate better performance. The total summed-ranks range from 7 - 210 (7 outcomes x N=30). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in NAB: Part A | change from baseline and 10 weeks | Neuropsychological Assessment Battery Numbers & Letters A Efficiency \| T-score\| age & education normed\| range 19-70 Higher scores mean a better outcome. |
| Change in NAB: Part D | change from baseline and 10 weeks | Neuropsychological Assessment Battery Numbers & Letters D Efficiency \| T-score\| age & education normed\| range 19-70 Higher scores mean a better outcome. |
| Change in D-KEFS: Inhibition Time | change from baseline and 10 weeks | Delis-Kaplan Executive Function System Color-Word Inhibition Time \| Scaled \| age normed\| range 1-16 Higher scores mean a better outcome. |
| Change in PASAT | change from baseline and 10 weeks | Paced Auditory Serial Addition Test 3-second interstimulus interval \| Z-score\| age & education normed\| range -5 to +5 Higher scores mean a better outcome. |
| Change in D-KEFS: Number-Letter Switching Time | change from baseline and 10 weeks | Delis-Kaplan Executive Function System Trail Making Number/Letter Switching \| Scaled \| age normed\| range 1-16 Higher scores mean a better outcome. |
| Change in WAIS-IV: Digit Span | change from baseline and 10 weeks | Wechsler Adult Intelligence Scale, fourth edition Digit Span \| Scaled \| age\| 1-16 Higher scores mean a better outcome. |
| Change in D-KEFS: Inhibition-Switching Time | change from baseline and 10 weeks | Delis-Kaplan Executive Function System Color-Word Inhibition/Switching \| Scaled \| age normed\| range 1-16 Higher scores mean a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine The study drug target dose is Atomoxetine (ATM) 80 milligram (mg) per day; given as a once daily dose of an 80mg capsule. Patients will titrate up to target dose by starting on ATM 40mg capsules: 1 capsule daily for 14 days. Following study visit 3 (after 2 weeks on the titration dose), patients will increase the dose of ATM to 80mg daily.
Atomoxetine: The study drug target dose is ATM 80mg per day; given as a once daily dose of an 80mg capsule. Patients will titrate up to target dose by starting on ATM 40mg capsules: 1 capsule daily for 14 days. Following study visit 3 (after 2 weeks on the titration dose), patients will increase the dose of ATM to 80mg daily. | 15 |
| Placebo Patients in the placebo arm will follow the same titration schedule as those in the active arm. Patients will titrate up to target dose by starting 40mg capsules: 1 capsule daily for 14 days. Following study visit 3 (after 2 weeks on the titration dose), patients will increase the dose to 80mg daily.
Placebo | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Atomoxetine | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 6.5 | 66.8 years STANDARD_DEVIATION 7 | 66.7 years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 29 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 29 Participants | 14 Participants |
| Region of Enrollment United States | 15 Participants | 30 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 12 Participants | 22 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
The Global Statistical Test Combined Information on Change From Baseline on a Battery of Standardized Executive Function Tests
Patients were ranked on each outcome and ranks were summed. The mean summed-ranks were compared by treatment group by a global statistical test (GST). Higher scores indicate better performance. The total summed-ranks range from 7 - 210 (7 outcomes x N=30).
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Atomoxetine | The Global Statistical Test Combined Information on Change From Baseline on a Battery of Standardized Executive Function Tests | 99.5 summed-ranks |
| Placebo | The Global Statistical Test Combined Information on Change From Baseline on a Battery of Standardized Executive Function Tests | 117.5 summed-ranks |
Comparison: The primary comparison between ATM and placebo used O'Brien's Global Statistical Test (GST) to analyze change from baseline to 10 weeks for the set of neuropsychological measures included in the primary efficacy outcome.p-value: 0.25Global Statistical Test
Secondary
Change in D-KEFS: Inhibition-Switching Time
Delis-Kaplan Executive Function System Color-Word Inhibition/Switching \| Scaled \| age normed\| range 1-16 Higher scores mean a better outcome.
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change in D-KEFS: Inhibition-Switching Time | -0.87 units on a scale | Standard Deviation 1.63 |
| Placebo | Change in D-KEFS: Inhibition-Switching Time | -0.2 units on a scale | Standard Deviation 1.63 |
Secondary
Change in D-KEFS: Inhibition Time
Delis-Kaplan Executive Function System Color-Word Inhibition Time \| Scaled \| age normed\| range 1-16 Higher scores mean a better outcome.
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change in D-KEFS: Inhibition Time | -0.77 units on a scale | Standard Deviation 1.4 |
| Placebo | Change in D-KEFS: Inhibition Time | -0.3 units on a scale | Standard Deviation 1.17 |
Secondary
Change in D-KEFS: Number-Letter Switching Time
Delis-Kaplan Executive Function System Trail Making Number/Letter Switching \| Scaled \| age normed\| range 1-16 Higher scores mean a better outcome.
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change in D-KEFS: Number-Letter Switching Time | -0.9 units on a scale | Standard Deviation 1.33 |
| Placebo | Change in D-KEFS: Number-Letter Switching Time | -0.67 units on a scale | Standard Deviation 1.43 |
Secondary
Change in NAB: Part A
Neuropsychological Assessment Battery Numbers & Letters A Efficiency \| T-score\| age & education normed\| range 19-70 Higher scores mean a better outcome.
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change in NAB: Part A | -0.71 units on a scale | Standard Deviation 1.05 |
| Placebo | Change in NAB: Part A | -0.23 units on a scale | Standard Deviation 1.07 |
Secondary
Change in NAB: Part D
Neuropsychological Assessment Battery Numbers & Letters D Efficiency \| T-score\| age & education normed\| range 19-70 Higher scores mean a better outcome.
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change in NAB: Part D | -0.35 units on a scale | Standard Deviation 1.31 |
| Placebo | Change in NAB: Part D | -0.11 units on a scale | Standard Deviation 0.75 |
Secondary
Change in PASAT
Paced Auditory Serial Addition Test 3-second interstimulus interval \| Z-score\| age & education normed\| range -5 to +5 Higher scores mean a better outcome.
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change in PASAT | -0.96 units on a scale | Standard Deviation 1.96 |
| Placebo | Change in PASAT | 0.42 units on a scale | Standard Deviation 1.22 |
Secondary
Change in WAIS-IV: Digit Span
Wechsler Adult Intelligence Scale, fourth edition Digit Span \| Scaled \| age\| 1-16 Higher scores mean a better outcome.
Time frame: change from baseline and 10 weeks
Population: Intent-to-treat sample of all patients randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change in WAIS-IV: Digit Span | -0.17 units on a scale | Standard Deviation 0.8 |
| Placebo | Change in WAIS-IV: Digit Span | 0 units on a scale | Standard Deviation 0.67 |