Effects of Atomoxetine in Mild Cognitive Impairment
Condition: Mild Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the safety of atomoxetine and its effect primarily
      on 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).
      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 study will also explore rates of change in biomarkers of
      neurodegeneration (Aß, tau, brain atrophy rates). The results of this research will help
      determine if atomoxetine alters signs of inflammation and other biomarkers associated with
      Alzheimer's disease.
    

Detailed description: 
      The Alzheimer's Disease (AD) epidemic is a looming crisis, with an urgent need for new
      therapies to delay or prevent symptom onset and progression. Advances in AD biomarker
      research have demonstrated changes in amyloid, brain metabolism, and other pathophysiologies
      prior to the onset of memory loss, with some markers possibly changing one or two decades
      earlier. Since MCI coincides with the onset of brain atrophy, this early stage of AD
      pathogenesis may offer a critical window of time to initiate novel therapies aimed at the
      secondary wave of events that lead to progressive neurodegeneration.

      From recently emerged basic research in animal models of AD: loss of norepinephrine (NE)
      incites a pro-inflammatory condition that is neurotoxic and reduces Aß clearance, and
      remarkably, rescue of norepinephrine reverses these effects and slows neurodegeneration. This
      study seeks to extend this proof-of-concept to humans for the first time. The study proposes
      that atomoxetine, a selective norepinephrine transport inhibitor, is an ideal drug to
      translate these findings to humans because it is already FDA-approved and safe in the elderly

      Subjects with mild cognitive impairment (amnestic or multi-domain subtypes) will be randomly
      assigned to treatment with placebo or flexible doses of the Norepinephrine Transporter (NET)
      inhibitor atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a
      maximum of 100 mg po daily or the maximum tolerated dose. Participants will be treated for
      upto 29 weeks, and will undergo venous blood draws and lumbar puncture for biomarker analyses
      at baseline and up to weeks 29. At a maximum of 29 weeks time point, subjects assigned to
      active treatment will crossover to placebo and those subjects who were initially randomized
      to placebo will initiate active treatment.

      Participants who complete study are eligible to receive open-label Atomoxetine at the
      maximum-tolerated dose received during the double-blind phase of the trial. Subjects in the
      open label are seen every at week 29 upto maximum of 2 years.
    

Intervention name(s): Atomoxetine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects in this intervention will receive Atomoxetine up to 29 weeks, crossover, dose escalating (up to a maximum dose of 100 mg per day) of oral atomoxetine; Subjects in this intervention will receive inactive compound up to weeks 29 and will cross over to the other group
Other intervention name(s): Strattera; Primary Outcome Measure; Inactive compound
Intervention MeSH terms: Atomoxetine Hydrochloride
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Mild Cognitive Impairment; Memory Loss; Alzheimer's Disease