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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Cognitive Impairment
• Intervention / Treatment: Drug: Placebo; Drug: Atomoxetine

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: 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.; Other Names: Strattera
Placebo Comparator: 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.	Drug: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Vanessa K Hinson, MD, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: November 28, 2012
• First Submitted That Met QC Criteria: November 29, 2012
• First Posted (Estimate): November 30, 2012

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: July 25, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Parkinson's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Parkinson Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: ATM-Cog

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No