Atomoxetine Treatment for Cognitive Impairment in Parkinson's Disease (ATM-Cog)

Study Overview
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Brief Summary
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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.

Official Title
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Atomoxetine Treatment for Cognitive Impairment in Parkinson's Disease (ATM-Cog)

Conditions
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Parkinson's Disease, Cognitive Impairment

Intervention / Treatment
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* Drug: Atomoxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atomoxetine<br>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. | Drug: Atomoxetine<br>* 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.<br>* Other names: Strattera;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | change from baseline and 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | change from baseline and 10 weeks | 
| 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. | change from baseline and 10 weeks | 
| 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. | change from baseline and 10 weeks | 
| 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. | change from baseline and 10 weeks | 
| 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. | change from baseline and 10 weeks | 
| 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. | change from baseline and 10 weeks | 
| Change in WAIS-IV: Digit Span | Wechsler Adult Intelligence Scale, fourth edition Digit Span | Scaled | age| 1-16 Higher scores mean a better outcome. | change from baseline and 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease