NCT03091400

Recall Enhancement Through Treatment With Atomoxetine in MS (RETAIN-MS)

Phase Two Randomized Controlled Crossover Trial of Atomoxetine to Treat Memory Impairment Due to Multiple Sclerosis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Icahn School of Medicine at Mount Sinai · Academic / Other
• Sex: All
• Age: 21 Years – 60 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Memory Disorders
• Multiple Sclerosis

Interventions

Type	Name	Description
DRUG	Atomoxetine	Atomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks)
DRUG	Placebo	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)

Timeline

• Start date: 2017-03-16
• Primary completion: 2018-06-11
• Completion: 2018-06-11
• First posted: 2017-03-27
• Last updated: 2020-03-13
• Results posted: 2020-03-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study