Cognitive Decline, Multiple Sclerosis
Conditions
Brief summary
A DIGITAL THERAPEUTIC TO IMPROVE THINKING IN MULTIPLE SCLEROSIS WHO: 65 participants with a confirmed diagnosis of Multiple Sclerosis (MS) WHY: Purpose of the study is to compare the effect of 2 tablet-based brain training digital tools on important components of thinking (cognition). WHAT: Complete a set of tests (physical and cognitive) at baseline, 6 weeks and 14 weeks, and use one of two brain training tools on an iPad in your home, for 25 minutes a day, 5 days a week, for 6 weeks. WHERE: UCSF WEILL INSTITUTE FOR NEUROSCIENCES (675 Nelson Rising Lane, San Francisco, CA)
Detailed description
The purpose of this study is to begin to test a brain training video game in people with Multiple Sclerosis (MS). Visit 1. After informed consent, you will complete a series of questions about your functioning and mood. You will then complete a series of tests (vision, hand tapping, walking). Then, you will complete a set of thinking tests. The first set will be paper and pencil. The second set will be on a tablet or a computer. You will use your study code to sign into these tools and you won't provide any personal details for the digitized tests. Finally, you will complete the cognitive training tool. There are two versions of this digital, iPad based tool, which takes about 25 minutes to complete and is designed to be entertaining. You will be randomized into 1 of 2 groups: each group will play a version of the brain training game. You will not be told what group/game type you were randomized into. You will be given the tablet with the game on it to take home, and to practice this game 5 times a week for 6 weeks. Visit 2. After the 6 weeks of at-home training, you will then come back to the research study unit to do a repeat of the initial visit (with physical and cognitive assessments). At this study visit, you will also be returning the iPad. Visit 3. You will then return 8 weeks after Visit 2, to do a repeat of the assessments. You will be compensated for each study visit (visit 1: $50, visit 2: $100, visit 3: $150).
Interventions
DEVICETablet-based Game
Tablet-based game aimed at improving processing speed and attention.
Sponsors
Akili Interactive Labs, Inc.
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Study assessment administrator is blinded to what digital tool the subject has been assigned.
Eligibility
Sex/Gender
ALL
Age
18 Years to 71 Years
Healthy volunteers
No
Inclusion criteria
* Adult men or women diagnosed with multiple sclerosis (MS) or clinically isolated syndrome (CIS) * SDMT z-score range (-2 to +1) * Wifi available in home * Able to use a tablet (iPad) * Able to attend 3 study visits in person.
Exclusion criteria
* Clinician's assessment of visual, cognitive, or motor impairment that would preclude participation. * A clinical relapse within the last 30 days. * Steroid treatment for clinical relapse within the last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Processing Speed After 6 Weeks of Treatment With a Digital Therapeutic 'Game 1', vs. 'Game 2'. | Baseline and 6 weeks | Processing speed is being measured by the Symbol Digit Modalities Test (SDMT) score. SDMT measures the time to pair abstract symbols with specific numbers. The test requires visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items in 90 seconds. (max=110, min=0). Higher scores indicate improvement. Lower scores indicate worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least 4-point Increase in SDMT Above Their Baseline Value 8 Weeks After Treatment | 14 weeks | Number of participants showing a clinically meaningful 4+ point increase in SDMT (symbol digit modalities test) relative to baseline SDMT score. Comparison of SDMT changes 8 weeks after end of treatment with Tool 1 vs. Tool 2. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2 | Baseline and 6 weeks | Comparison of changes in mood (depression, anxiety). Depression measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Possible range of scores is zero to 60, with the higher scores indicating the presence of more symptomatology. Anxiety measured using the State-Trait Anxiety Inventory - State subtest (STAI-S) and the State-Trait Anxiety Inventory - Trait subtest (STAI-T). Both have 20 questions and a score range 20-80, with higher scores indicating greater anxiety. |
| Change in Fatigue After 6 Weeks Treatment With Game 1 vs. Game 2. | Baseline and 6 weeks | Fatigue is being measured by the Modified Fatigue Impact Scale (MFIS) which has participants rank 21 items on 1 to 4 (never to always) scale. The score is the sum of these subscales. (max=84, min=0) Lower scores indicate improvement. Higher scores indicate worsening. |
| Change in a Digital Cognitive Battery After 6 Weeks Treatment With Game 1 vs. Game 2. | Baseline and 6 weeks | Comparison of changes in scores on Match, a tablet-based assessment of processing speed and executive function. Performance is gauged on a continuous scale using the total number of correct responses given in 2-minutes. The minimum possible score is 0 (no correct responses) with higher scores indicating better performance (no maximum possible score). |
| Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | Baseline and 6 weeks | Comparison of changes in cognition, as assessed using the BICAMS battery (Brief International Cognitive Assessment for Multiple Sclerosis) and PASAT (Paced Auditory Serial Addition Test). The BICAMS battery is composed of 3 tests (for all, higher scores indicate better performance): (1) The Symbol Digit Modalities Test (SDMT), a measure of information processing speed where performance is gauged by the number of correct responses given in 90-seconds, with a minimum possible score of 0 and maximum of 110. (2) The California Verbal Learning Test-II (CVLT-II) is a 5-trial auditory/verbal learning test with a total min. score of 0 and max of 80. (3) The Brief Visuospatial Memory Test -- Revised (BVMT-R) is a visual and spatial memory test given in 3 trials with a total min score of 0 and max of 36. The PASAT is a test of information processing and attention with a minimum score of 0 and maximum of 60. Higher scores indicate better performance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AKL-T03 Tablet-based game aimed at improving processing speed and attention. | 23 |
| AKL-T09 Control, tablet-based word finding game | 21 |
| Total | 44 |
Baseline characteristics
| Characteristic | AKL-T09 | Total | AKL-T03 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 7 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 37 Participants | 18 Participants |
| Age, Continuous | 49.2 years STANDARD_DEVIATION 10.9 | 51.1 years STANDARD_DEVIATION 12.6 | 52.9 years STANDARD_DEVIATION 14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 18 Participants | 35 Participants | 17 Participants |
| Region of Enrollment United States | 21 participants | 44 participants | 23 participants |
| Sex: Female, Male Female | 18 Participants | 35 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 9 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change in Processing Speed After 6 Weeks of Treatment With a Digital Therapeutic 'Game 1', vs. 'Game 2'.
Processing speed is being measured by the Symbol Digit Modalities Test (SDMT) score. SDMT measures the time to pair abstract symbols with specific numbers. The test requires visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items in 90 seconds. (max=110, min=0). Higher scores indicate improvement. Lower scores indicate worsening.
Time frame: Baseline and 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T03 | Change in Processing Speed After 6 Weeks of Treatment With a Digital Therapeutic 'Game 1', vs. 'Game 2'. | 6.10 score on a scale | Standard Deviation 4.62 |
| AKL-T09 | Change in Processing Speed After 6 Weeks of Treatment With a Digital Therapeutic 'Game 1', vs. 'Game 2'. | 3.55 score on a scale | Standard Deviation 7.51 |
Secondary
Number of Participants With at Least 4-point Increase in SDMT Above Their Baseline Value 8 Weeks After Treatment
Number of participants showing a clinically meaningful 4+ point increase in SDMT (symbol digit modalities test) relative to baseline SDMT score. Comparison of SDMT changes 8 weeks after end of treatment with Tool 1 vs. Tool 2.
Time frame: 14 weeks
Population: 39 participants (97.5%) returned for Visit 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AKL-T03 | Number of Participants With at Least 4-point Increase in SDMT Above Their Baseline Value 8 Weeks After Treatment | 14 Participants |
| AKL-T09 | Number of Participants With at Least 4-point Increase in SDMT Above Their Baseline Value 8 Weeks After Treatment | 7 Participants |
Other Pre-specified
Change in a Digital Cognitive Battery After 6 Weeks Treatment With Game 1 vs. Game 2.
Comparison of changes in scores on Match, a tablet-based assessment of processing speed and executive function. Performance is gauged on a continuous scale using the total number of correct responses given in 2-minutes. The minimum possible score is 0 (no correct responses) with higher scores indicating better performance (no maximum possible score).
Time frame: Baseline and 6 weeks
Population: Match data was unavailable for some participants (n = 6, 3 per group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T03 | Change in a Digital Cognitive Battery After 6 Weeks Treatment With Game 1 vs. Game 2. | 0.94 number of correct responses | Standard Deviation 3.54 |
| AKL-T09 | Change in a Digital Cognitive Battery After 6 Weeks Treatment With Game 1 vs. Game 2. | 0.35 number of correct responses | Standard Deviation 4.66 |
Other Pre-specified
Change in Fatigue After 6 Weeks Treatment With Game 1 vs. Game 2.
Fatigue is being measured by the Modified Fatigue Impact Scale (MFIS) which has participants rank 21 items on 1 to 4 (never to always) scale. The score is the sum of these subscales. (max=84, min=0) Lower scores indicate improvement. Higher scores indicate worsening.
Time frame: Baseline and 6 weeks
Population: Missing fatigue survey data (MFIS) for 2 participants, 1 per study group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T03 | Change in Fatigue After 6 Weeks Treatment With Game 1 vs. Game 2. | -4.79 score on a scale | Standard Deviation 6.27 |
| AKL-T09 | Change in Fatigue After 6 Weeks Treatment With Game 1 vs. Game 2. | -2.95 score on a scale | Standard Deviation 9.55 |
Other Pre-specified
Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2
Comparison of changes in mood (depression, anxiety). Depression measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Possible range of scores is zero to 60, with the higher scores indicating the presence of more symptomatology. Anxiety measured using the State-Trait Anxiety Inventory - State subtest (STAI-S) and the State-Trait Anxiety Inventory - Trait subtest (STAI-T). Both have 20 questions and a score range 20-80, with higher scores indicating greater anxiety.
Time frame: Baseline and 6 weeks
Population: Missing data for 6 participants on trait anxiety (STAI-T), 3 per study group; as well as for 2 participants on depression (CES-D) and state anxiety (STAI-S) measures, 1 per study group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKL-T03 | Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2 | Depression (CES-D) | 1.11 score on a scale | Standard Deviation 6.14 |
| AKL-T03 | Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2 | Anxiety - State (STAI-S) | .05 score on a scale | Standard Deviation 4.64 |
| AKL-T03 | Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2 | Anxiety - Trait (STAI-T) | .77 score on a scale | Standard Deviation 4.1 |
| AKL-T09 | Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2 | Depression (CES-D) | -.90 score on a scale | Standard Deviation 5.57 |
| AKL-T09 | Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2 | Anxiety - State (STAI-S) | .21 score on a scale | Standard Deviation 8.93 |
| AKL-T09 | Change in Mood After 6 Weeks Treatment With Game 1 vs. Game 2 | Anxiety - Trait (STAI-T) | .35 score on a scale | Standard Deviation 3.35 |
Other Pre-specified
Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2.
Comparison of changes in cognition, as assessed using the BICAMS battery (Brief International Cognitive Assessment for Multiple Sclerosis) and PASAT (Paced Auditory Serial Addition Test). The BICAMS battery is composed of 3 tests (for all, higher scores indicate better performance): (1) The Symbol Digit Modalities Test (SDMT), a measure of information processing speed where performance is gauged by the number of correct responses given in 90-seconds, with a minimum possible score of 0 and maximum of 110. (2) The California Verbal Learning Test-II (CVLT-II) is a 5-trial auditory/verbal learning test with a total min. score of 0 and max of 80. (3) The Brief Visuospatial Memory Test -- Revised (BVMT-R) is a visual and spatial memory test given in 3 trials with a total min score of 0 and max of 36. The PASAT is a test of information processing and attention with a minimum score of 0 and maximum of 60. Higher scores indicate better performance.
Time frame: Baseline and 6 weeks
Population: Missing PASAT data for 3 participants, 2 in AKL-T03 and 1 in AKL-T09. Data for other measures (SDMT, BVMT-R and CVLT-II) were collected from all participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKL-T03 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | SDMT | 6.10 score on a scale | Standard Deviation 4.62 |
| AKL-T03 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | CVLT-II | 2.05 score on a scale | Standard Deviation 9.14 |
| AKL-T03 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | BVMT-R | 0.70 score on a scale | Standard Deviation 4.47 |
| AKL-T03 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | PASAT | 2.72 score on a scale | Standard Deviation 5.41 |
| AKL-T09 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | PASAT | 2.53 score on a scale | Standard Deviation 7.19 |
| AKL-T09 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | SDMT | 3.55 score on a scale | Standard Deviation 7.51 |
| AKL-T09 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | BVMT-R | 3.25 score on a scale | Standard Deviation 5.23 |
| AKL-T09 | Change in Paper and Pencil Cognitive Testing After 6 Weeks Treatment With Game 1 vs. Game 2. | CVLT-II | 5.20 score on a scale | Standard Deviation 8.6 |