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

Phase 2

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Atomoxetine	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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 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: 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 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 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.