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

NCT ID: NCT03091400

Last Updated: 2020-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-16
• Study Completion Date: 2018-06-11

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Atomoxetine

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

Group Type: EXPERIMENTAL

Atomoxetine

Intervention Type: DRUG

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

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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)

Interventions

Atomoxetine

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

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Strattera (Eli Lilly)

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Multiple Sclerosis based on the Revised McDonald criteria
• Age 21 - 60 years.
• Patient self-report of memory decline from previously higher level of functioning.
• Memory Impairment on validated neuropsychological memory screening tests, as follows:

1. performance ≤16th percentile on both (i) Rey Auditory Verbal Learning Test (RAVLT) Total Learning (TL) and (ii) WMS-IV Visual Reproduction I (VR-I); and b) mean normative memory performance (RAVLT TL and WMS-IV VR-I) is at least 1.0 standard deviation below expectations based on the Wechsler Test of Adult Reading (WTAR)

Exclusion Criteria

• Current stimulant medication usage.
• Previous diagnosis or treatment for ADHD or any neurologic condition other than multiple sclerosis (e.g., traumatic brain injury, epilepsy)
• Clinical relapse of MS within 60 days of screening,
• Change in disease-modifying therapy within 90 days of screening,
• Below average estimated premorbid intelligence (WTAR, < 16th percentile),
• Severe cognitive impairment indicated by a Mini-Mental Status Examination (MMSE) < 24/30.
• Contraindications for atomoxetine use: (a) self-reported history of suicidal ideation within the last twelve months (Columbia Suicide Severity Rating Scale), (b) diagnosis of bipolar illness, (c) moderate or severe current depressive symptomatology (Beck Depression Inventory Fast Screen ≥ 9), (d) diagnosis of hepatic disease, (e) narrow angle glaucoma, (f) pheochromocytoma, (g) monoamine oxidase inhibitor within 14 days of study drug start, (h) taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine), (i) diagnosis of heart disease, (j) pregnant or planning pregnancy during the study period, (k) breastfeeding, (l) hypersensitivity to atomoxetine or component of formulation.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

James F. Sumowski

Assoicate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James F Sumowski, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

GCO 16-1552

Identifier Type: -

Identifier Source: org_study_id