Recall Enhancement Through Treatment With Atomoxetine in MS (RETAIN-MS)
Condition: Memory Disorders; Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Memory Disorders; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this crossover trial is to investigate whether atomoxetine (versus placebo)
      improves memory function in persons with memory deficits due to multiple sclerosis.
    

Detailed description: 
      Approximately half of persons with multiple sclerosis (MS) develop memory decline, which
      makes it difficult to maintain gainful employment, manage a household, and lead a
      fully-engaged social life. There are currently no validated symptomatic treatments for memory
      deficits in persons with MS. The study team will perform a fourteen week double-blind
      phase-two crossover randomized controlled trial (RCT) of atomoxetine (80mg qd, six weeks)
      versus placebo (six weeks) to improve memory in MS patients with documented memory impairment
      (two-week washout between phases). Atomoxetine is a non-stimulant selective norepinephrine
      reuptake inhibitor FDA-approved to treat cognitive-behavioral symptoms of attention deficit /
      hyperactivity disorder (ADHD; Strattera, Eli Lilly). Pre-clinical evidence suggests that
      atomoxetine may also improve memory by targeting brain mechanisms responsible for memory
      function (norepinephrine in the hippocampus). Twenty-four MS patients demonstrating objective
      memory impairment on neuropsychological screening tests will be randomly assigned to
      once-daily orally-administered atomoxetine or identically-encapsulated placebo. After a
      two-week washout period, patients will be switched to the opposite condition. The RCT will be
      performed at the Corinne Goldsmith Dickinson Center for MS at the Icahn School of Medicine at
      Mount Sinai. Baseline and follow-up evaluations will assess change in objective memory
      function (Primary Outcome), as well as Secondary Outcomes of patient-reported memory change,
      additional objective measures of memory function, and a measure of speeded symbol-digit
      coding (the most widely-used test of cognition in persons with MS). Tertiary / Other Outcomes
      examine sustained attention, processing speed, working memory, fatigue, mood, manual
      dexterity, and walking speed. The researchers predict that atomoxetine will lead to
      significantly greater improvements in Primary and Secondary memory outcomes relative to
      placebo. Consistent with the ADHD literature, there may be additional benefits of atomoxetine
      versus placebo on measures of attention, processing speed, and working memory. Results of
      this phase 2 trial will inform decisions / planning for a possible phase 3 trial, which may
      ultimately support the use of non-stimulant, once-daily atomoxetine as a memory treatment
      option for MS patients.
    

Intervention name(s): Atomoxetine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Atomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks); Identically encapsulated placebo, with dose matched to experimental agent (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks)
Other intervention name(s): Strattera (Eli Lilly)
Intervention MeSH terms: Atomoxetine Hydrochloride
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Memory Disorders; Multiple Sclerosis; Atomoxetine Hydrochloride