Memory DisordersPhase 2NCT03091400
Recall Enhancement Through Treatment With Atomoxetine in MS (RETAIN-MS)
A Phase 2 study testing Atomoxetine in people with Memory Disorders and Multiple Sclerosis, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 60 years
- Conditions the study is for
- Memory Disorders, Multiple Sclerosis
- What is being tested?
- Atomoxetine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Mar 2017to 11 Jun 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Phase Two Randomized Controlled Crossover Trial of Atomoxetine to Treat Memory Impairment Due to Multiple Sclerosis
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.
Read the 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
- Being tested
- Atomoxetine, Placebo
- Keywords
- Memory Disorders, Multiple Sclerosis, Atomoxetine Hydrochloride
- Medical subject headings
- Memory Disorders, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtomoxetineDrug
Also called Strattera (Eli Lilly)
Atomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks)
PlaceboDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Atomoxetine | Experimental | Atomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks) Receives: Drug: Atomoxetine |
| Placebo | Placebo comparator | 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline and 14 weeks
Secondary outcomes (5)
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: baseline and 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start16 Mar 2017
- Primary completion11 Jun 2018
- Study completion11 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Memory DisordersStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James F. Sumowski, Icahn School of Medicine at Mount Sinai
- Investigators
- James F Sumowski, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03091400
- Sponsor's protocol ID
- GCO 16-1552
- Status last verified
- Feb 2020
- First submitted
- 16 Mar 2017
- Last updated
- 13 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Two Randomized Controlled Crossover Trial of Atomoxetine to Treat Memory Impairment Due to Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT03091400
- Acronym / sponsor ID
- GCO 16-1552
- Conditions
- Memory Disorders, Multiple Sclerosis
- Keywords
- Memory Disorders, Multiple Sclerosis, Atomoxetine Hydrochloride
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- 16 Mar 2017 (actual)
- Primary completion
- 11 Jun 2018 (actual)
- Study completion
- 11 Jun 2018 (actual)
- First posted
- 27 Mar 2017 (actual)
- Results
- Posted 13 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atomoxetine | Experimental | Drug: AtomoxetineAtomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks) |
| Placebo | Placebo comparator | Drug: PlaceboIdentically 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) |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (7 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtomoxetineAlso: Strattera (Eli Lilly)Atomoxetine (40 mg qd titration dose for first seven days, followed by 80 mg qd target dose for remaining five weeks) | Drug | Atomoxetine |
| PlaceboIdentically 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 |
Primary outcome
Change in Memory Change
Time frame: baseline and 14 weeks
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.
5 secondary outcomes
Change in Patient-Reported Memory Change
Time frame: baseline and 14 weeks
Change in CANTAB Paired Associate Learning
Time frame: baseline and 14 weeks
Change in NIH Toolbox Picture Sequence Memory Test
Time frame: baseline and 14 weeks
Change in Perceived Deficits Questionnaire (PDQ)
Time frame: baseline and 14 weeks
Change in Symbol Digit Modalities Test
Time frame: baseline and 14 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James F Sumowski, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atomoxetine in people with Memory Disorders and Multiple Sclerosis, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Memory Change (time frame: baseline and 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2020.