Effects of Atomoxetine in Mild Cognitive Impairment (ATX-001)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Allan I Levey, MD, Emory University
ClinicalTrials.gov Identifier:
NCT01522404
First received: January 25, 2012
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to find out if atomoxetine causes a change in the biologic markers (substances that may indicate the presence of a disease) in the cerebrospinal fluid (CSF) of participants diagnosed with Mild Cognitive Impairment (MCI). In this research study, the spinal fluid of subjects with MCI who take atomoxetine will be compared to spinal fluid of those who take capsules containing inactive material, also known as placebo. At the six-month timepoint, subjects who were taking placebo during the first six months will be placed on active study medication, and those who received active study medication will be reassigned to placebo. After completion of the study, subjects will be able to receive open-label atomoxetine.

This study will also evaluate if the drug is safe and well-tolerated. Additionally, information will be gathered to identify the dose of atomoxetine that is most beneficial, and how taking this medication affects thinking and behavior, as well as imaging and blood biomarkers. The results of this research will help determine if atomoxetine alters signs of inflammation and other biomarkers associated with Alzheimer's disease.


Condition Intervention Phase
Mild Cognitive Impairment
Drug: Atomoxetine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A 6 Month, Phase II Randomized, Double-Blind, Placebo Controlled, Flexible Dosing, Crossover Trial of Atomoxetine in Subjects With Mild Cognitive Impairment.

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Cerebrospinal fluid biomarkers of inflammation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Biomarkers of noradrenergic function [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Adverse Events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Cerebrospinal fluid biomarkers of neurodegeneration [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Imaging biomarkers of neurodegeneration [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Cognitive measures [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Behavioral symptoms [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atomoxetine
Active treatment
Drug: Atomoxetine
6 month, crossover, dose escalating (up to a maximum dose of 100 mg per day) of oral atomoxetine
Other Names:
  • Statterra
  • Primary Outcome Measure
Placebo Comparator: Inactive compound Drug: Placebo
At the six-month timepoint, subjects who were taking placebo during the first six months will be placed on active study medication.
Other Name: Inactive compound

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • Subjective memory concern per subject, study partner or clinician
  • Clinician diagnosis of amnestic MCI; single or multi-domain
  • Abnormal memory per Logical Memory subscale from Wechsler Memory Scale-Revised
  • MMSE score 24-30 inclusive. Exceptions considered for <8 yrs.education
  • Clinical Dementia Rating 0.5. Memory Box score must be >=0.5
  • General cognition & functional performance preserved
  • Cholinesterase inhibitors & memantine, if stable x12 wks.
  • Stability of medications x4 wks. May washout from psychoactive medication x4 wks.
  • Geriatric Depression Scale ≤6
  • Male/female outpatients aged 50-90 (inclusive)
  • Study partner has regular contact w/ subject, can provide reliable assessment of subject's level of function, & can be available for all visits, either in person or by telephone, throughout trial
  • Visual & auditory acuity adequate for testing
  • Good general health
  • Women of child-bearing potential willing to use medically acceptable birth control or practice abstinence throughout trial
  • Modified Rosen Hachinski ≤4
  • Completed 6th grade or has good work history
  • Fluent in English
  • Able to understand nature of study. Must provide written informed consent prior to conduct of any study procedures
  • Willing to undergo repeated MRIs & PET scans
  • Agrees to APOE, CYP2D6 & biomarker testing
  • Agrees to 3 lumbar punctures over course of study

Exclusion

  • Significant neurologic disease other than MCI
  • Screening/baseline MRI scan w/ evidence of infection, large vessel infarction or other focal structural lesion that could account for memory deficits. Subjects w/ multiple lacunes or lacunes in a critical memory structure
  • Contraindication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, or excessive weight)
  • Clinically significant suicide risk, based on MD's judgment per structured clinician interview. Suicide attempt within past yr.
  • Major depression, bipolar disorder within past yr., or history of schizophrenia. Psychotic features, agitation or behavioral problems within last 3 mos.
  • History of alcohol or substance abuse/dependence within past 2 yrs.
  • Allergic to atomoxetine
  • Uncontrolled medical condition that may preclude completion of study, or medical condition which would represent contraindication to atomoxetine (e.g. hepatic insufficiency, untreated hypertension, untreated cardiovascular or cerebrovascular disease)
  • Known serious cardiac problems. History of narrow angle glaucoma. History of pheochromocytoma
  • Clinically significant abnormal findings on screening lab tests or exam. Abnormalities in Vitamin B12 level, TFTs or LFTs that may interfere w/ study. Low Vitamin B12 level (unless homocysteine & methylmalonic acid indicate no clinical significance)
  • Slow metabolizer of atomoxetine
  • Women who are pregnant or lactating, or plan to become pregnant during study
  • Behavioral symptoms requiring current use of neuroleptics, chronic anxiolytics, sedative hypnotics
  • Current use of warfarin
  • Inability to obtain initial Cerebrospinal fluid sample
  • Use within 60 days of a monoamine oxidase inhibitor or potent CYP2D6 inhibitor
  • Current use of anti-psychotics or the following anti-depressant medications: duloxetine, venlafaxine, desvenlafaxine, imipramine, amitryptiline
  • Current participation in another clinical trial.
  • Current/recent participation in procedures involving radioactive agents such that total radiation dose exposure to subject in any given year > limits of annual & total dose commitment set forth in US CFR Title 21 Section 361.1
  • Cerebrospinal fluid profile inconsistent with underlying AD pathology
  • Reasonable likelihood for non-compliance w/ protocol or any other reason, in opinion of investigator
  • Exceptions may be considered on individual basis at discretion of protocol director
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522404

Contacts
Contact: Margaret L Walker, Ph.D. 404-728-6942 mlwalke@emory.edu

Locations
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Sub-Investigator: James J. Lah, MD, PhD         
Sub-Investigator: William T. Hu, MD, PhD         
Sub-Investigator: Janet S. Cellar, DNP         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Allan I. Levey, MD, PhD Emory University
  More Information

No publications provided

Responsible Party: Allan I Levey, MD, Professor and Chair, Department of Neurology, Emory University
ClinicalTrials.gov Identifier: NCT01522404     History of Changes
Other Study ID Numbers: IRB00054397, 5U01AG010483, ATX-001
Study First Received: January 25, 2012
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Mild Cognitive Impairment
Memory Loss
Alzheimer's Disease

Additional relevant MeSH terms:
Mild Cognitive Impairment
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Atomoxetine
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014