A Phase 2 interventional study of Atomoxetine and Placebo in Memory Disorders and Multiple Sclerosis, sponsored by Icahn School of Medicine at Mount Sinai. Completed at 1 site in United States. Open to participants aged 21 Years to 60 Years. Per ClinicalTrials.gov, last updated 2020-03-13.
Sponsored by Icahn School of Medicine at Mount Sinai · Phase 2, Interventional, and Treatment
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.
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.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
This study's enrollment of 11 is below the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →Icahn School of Medicine at Mount Sinai is the lead sponsor of 764 studies on the registry; 181 are open to participants now.
Of its 121 completed or terminated interventional studies of FDA-regulated products, 82 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Memory Impairment on validated neuropsychological memory screening tests, as follows:
Exclusion Criteria:
Atomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks)
Drug: Atomoxetine
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)
Drug: Placebo
Atomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks)
Also known as: Strattera (Eli Lilly)
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)
Change in Memory Change
Composite memory function (mean normative z-score) across verbal memory and visuospatial memory tasks: (1) Selective Reminding Test (SRT) assesses verbal learning of a 12-item word list over six trials (a. Total Learning; possible raw score range of 0-72), and recall after a delay (b: Delayed Recall; possible raw score range of 0-36); (2) Brief Visuospatial Memory Test, Revised (BVMT-R; possible raw score range of 0-36) assesses learning of six geometric shapes in six locations over three trials (c. Total Learning), and recall after a delay (d. Delayed Recall; possible raw score range of 0-12). Results reported as composite memory at follow-up minus baseline. Higher scores indicate better outcomes.
Time frame: baseline and 14 weeks
Change in Patient-Reported Memory Change
Patients will endorse memory change over the past six weeks as: much improved (3), improved (2), slightly improved (1), unchanged (0), slightly worse (-1), worse (-2), much worse (-3).
Time frame: baseline and 14 weeks
Change in CANTAB Paired Associate Learning
CANTAB Paired Associate Learning (Total Errors Adjusted; possible raw score range of 0-70): a tablet-based memory task requiring subjects to study and recall the location of complex visual images not easily verbalized. Errors are tallied. Results reported as follow-up minus baseline. Higher scores indicate worse outcomes.
Time frame: baseline and 14 weeks
Change in NIH Toolbox Picture Sequence Memory Test
NIH Toolbox Picture Sequence Memory Test (possible raw score range of 0-31): a tablet-based task requiring subjects to study the sequence of many activity scenes (e.g., flying a kite) presented visually and audibly. Correct sequences tallied. Results reported as follow-up minus baseline. Higher scores indicate better outcomes.
Time frame: baseline and 14 weeks
Change in Perceived Deficits Questionnaire (PDQ)
Perceived Deficits Questionnaire (PDQ): the PDQ asks subjects to rate twenty cognitive difficulties on a scale from never (0) to almost always (4). Total ranges from 0-80. Results reported as follow-up minus baseline. Higher scores indicate worse outcomes. If a change is detected, will proceed to identify which of the four subscales were affected: retrospective memory, prospective memory, attention, planning / organization.
Time frame: baseline and 14 weeks
Change in Symbol Digit Modalities Test
Symbol Digit Modalities Test (Oral Version, total raw; possible range of 0-110): A test of processing speed requiring subjects to rapidly complete symbol-digit pairings based on a key. Incidental learning may contribute to performance. Total correct in 90 seconds is tallied. Results reported as follow-up minus baseline. Higher scores indicate better outcomes.
Time frame: baseline and 14 weeks
Enrollment Period: 03/16/2017 - 02/20/2018. There was a two-phase screening. Of the 35 participants who met initial screening criteria (e.g., age, MS diagnosis), 24 did not meet secondary screening requirements (e.g., objective memory impairment on assessment). Eleven (11) participants met secondary screening requirements and were randomized.
| Milestone | Atomoxetine Then Placebo | Placebo Then Atomoxetine |
|---|---|---|
| Started | 5 | 6 |
| Completed | 5 | 6 |
| Not completed | 0 | 0 |
| Milestone | Atomoxetine Then Placebo | Placebo Then Atomoxetine |
|---|---|---|
| Started | 5 | 6 |
| Completed | 4 | 6 |
| Not completed | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Milestone | Atomoxetine Then Placebo | Placebo Then Atomoxetine |
|---|---|---|
| Started | 4 | 6 |
| Completed | 4 | 6 |
| Not completed | 0 | 0 |
Composite memory function (mean normative z-score) across verbal memory and visuospatial memory tasks: (1) Selective Reminding Test (SRT) assesses verbal learning of a 12-item word list over six trials (a. Total Learning; possible raw score range of 0-72), and recall after a delay (b: Delayed Recall; possible raw score range of 0-36); (2) Brief Visuospatial Memory Test, Revised (BVMT-R; possible raw score range of 0-36) assesses learning of six geometric shapes in six locations over three trials (c. Total Learning), and recall after a delay (d. Delayed Recall; possible raw score range of 0-12). Results reported as composite memory at follow-up minus baseline. Higher scores indicate better outcomes.
| z-score | Atomoxetine | Placebo |
|---|---|---|
| Change in Memory Change | 0.32 ± 0.60 | 0.24 ± 0.46 |
Patients will endorse memory change over the past six weeks as: much improved (3), improved (2), slightly improved (1), unchanged (0), slightly worse (-1), worse (-2), much worse (-3).
| score on a scale | Atomoxetine | Placebo |
|---|---|---|
| Change in Patient-Reported Memory Change | 0.70 ± 1.16 | 0.90 ± 1.37 |
CANTAB Paired Associate Learning (Total Errors Adjusted; possible raw score range of 0-70): a tablet-based memory task requiring subjects to study and recall the location of complex visual images not easily verbalized. Errors are tallied. Results reported as follow-up minus baseline. Higher scores indicate worse outcomes.
| score on a scale | Atomoxetine | Placebo |
|---|---|---|
| Change in CANTAB Paired Associate Learning | -10.30 ± 11.98 | -8.10 ± 15.56 |
NIH Toolbox Picture Sequence Memory Test (possible raw score range of 0-31): a tablet-based task requiring subjects to study the sequence of many activity scenes (e.g., flying a kite) presented visually and audibly. Correct sequences tallied. Results reported as follow-up minus baseline. Higher scores indicate better outcomes.
| score on a scale | Atomoxetine | Placebo |
|---|---|---|
| Change in NIH Toolbox Picture Sequence Memory Test | 4.50 ± 5.80 | 3.20 ± 2.97 |
Perceived Deficits Questionnaire (PDQ): the PDQ asks subjects to rate twenty cognitive difficulties on a scale from never (0) to almost always (4). Total ranges from 0-80. Results reported as follow-up minus baseline. Higher scores indicate worse outcomes. If a change is detected, will proceed to identify which of the four subscales were affected: retrospective memory, prospective memory, attention, planning / organization.
| score on a scale | Atomoxetine | Placebo |
|---|---|---|
| Change in Perceived Deficits Questionnaire (PDQ) | -6.60 ± 9.97 | -5.90 ± 13.14 |
Symbol Digit Modalities Test (Oral Version, total raw; possible range of 0-110): A test of processing speed requiring subjects to rapidly complete symbol-digit pairings based on a key. Incidental learning may contribute to performance. Total correct in 90 seconds is tallied. Results reported as follow-up minus baseline. Higher scores indicate better outcomes.
| score on a scale | Atomoxetine | Placebo |
|---|---|---|
| Change in Symbol Digit Modalities Test | 7.20 ± 7.07 | 5.50 ± 5.42 |
Collected over 14 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Atomoxetine | 0/10 (0%) | 0/10 (0%) | 4/10 (40%) |
| Placebo | 0/10 (0%) | 0/10 (0%) | 1/10 (10%) |
| Event | Atomoxetine | Placebo |
|---|---|---|
| DiarrheaGastrointestinal disorders | 1/10 | 0/10 |
| DizzinessNervous system disorders | 1/10 | 0/10 |
| Abnormal dreamsPsychiatric disorders | 1/10 | 0/10 |
| FatigueGeneral disorders | 0/10 | 1/10 |
| Urinary HesitationRenal and urinary disorders | 1/10 | 0/10 |
| Pelvic/testicular painReproductive system and breast disorders | 1/10 | 0/10 |
| Painful UrinationRenal and urinary disorders | 1/10 | 0/10 |
| Age, Continuous(years) | Atomoxetine, Then Placebo | Placebo, Then Atomoxetine | Total |
|---|---|---|---|
| Mean | 42.0 ± 9.1 | 46.0 ± 5.4 | 44.4 ± 6.9 |
| Sex: Female, Male(Participants) | Atomoxetine, Then Placebo | Placebo, Then Atomoxetine | Total |
|---|---|---|---|
| Female | 1 | 2 | 3 |
| Male | 3 | 4 | 7 |
| Ethnicity (NIH/OMB)(Participants) | Atomoxetine, Then Placebo | Placebo, Then Atomoxetine | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 2 | 3 |
| Not Hispanic or Latino | 3 | 4 | 7 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Atomoxetine, Then Placebo | Placebo, Then Atomoxetine | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 1 | 4 |
| White | 1 | 5 | 6 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in Feb 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Icahn School of Medicine at Mount Sinai