Computer Assisted Cognitive Rehabilitation for Persons With Multiple Sclerosis
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: University of Texas at Austin

 
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Computer Assisted Cognitive Rehabilitation Intervention  
for Persons With Multiple Sclerosis 
 
NCT #03200899 
 
January 7, 2021 (revised) 
 
 
 
Investigators:  Alexa Stuifbergen, PhD, RN, Principal Investigator 
 
Co-investigators:  Heather Becker, PhD;  Francisco Perez, PhD 
 
 
 
 
 

 
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PROTOCOL AND PROPOSED STATISTICAL ANALYSIS:  
 
This study will test the effects of an intervention (MAPSS-MS) to promote the cognitive 
functioning of persons with MS. The effectiveness of the intervention will be examined using a 
prospective, longitudinal, randomized pretest/posttest usual care comparison group design. The 
intervention consists of an efficacy-building group intervention that will incorporate an 
individualized computer-based practice component (CACR) to help participants build self-
efficacy for skills to improve cognitive functioning and activities of daily living. The group 
component of the intervention will provide information specific to cognitive difficulties 
experienced with MS, help participants assess their difficulties and identify strategies to manage 
cognitive difficulties and improve performance. The group exercises will focus on helping 
persons translate the skills they are practicing in the CACR component into everyday life to 
improve overall functioning and health. 
 
Participants will be recruited from three metropolitan communities in Texas: Houston, San 
Antonio and Dallas/Fort Worth.  The Houston metro area has a population of over 5.9 million 
persons. The population is approximately 26% white/non-Hispanic, 44% Hispanic, 24% Black, 
and 6% Asian. The San Antonio metro area has a population of 2.2 million persons; 63% are 
Hispanic and 7% are African American.  More than 6.3 million people live in the Dallas/Fort 
Worth metroplex; 13% are African-American, 4% Asian or Pacific Islander and 21% are 
Hispanic or Latino of any race. The Lone Star Chapter of the National MS Society has active 
offices in each community to support recruitment and implementation. 
  
PI Stuifbergen and Co-I Perez have worked with staff of the Lone Star Chapter of the National 
MS Society for over 20 years and are well known by MS clinicians throughout the state.  The 
research team has substantial experience with conducting multi-site interventions and data 
collection (RO1HD035047, R21 NR011076; RO1 NR03195) with persons with MS. Use of the 
three communities will assure the ability to recruit sufficient participants and support the 
diversity of the sample (MS predominates in women and whites). Neurologists who are MS 
Specialists in each community have agreed to assist with recruitment (see letters of support) and 
serve as consultants for patient referral.  The Lone Star Chapter of the National MS Society 
serves more than 21,000 persons with MS in 174 counties in Texas including these communities.  
 
 
SAMPLE: The sample for this study will consist of persons with physician-diagnosed MS living 
in the identified Texas metropolitan areas who are concerned about their cognitive problems.  
 
SAMPLE SIZE: Power analyses were conducted using data from our recent preliminary study. 
The initial sample size estimate was based upon an f value of .38 for the interaction of time by 
group for the CVLT-Total. The alpha level was set at .01 to account for the multiple analyses that 

 
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are proposed to answer the research questions.  A minimum sample of 80 was estimated to have 
80% power to detect a statistically significant time x experimental group interaction with a .38 
effect size.  However, we propose to power the study based upon a lower f value of .28, which 
corresponds more closely to the effect sizes observed for the other neuropsychological tests.  
Therefore, 180 individuals will be needed to detect an effect size (f) of .28 as statistically 
significant.  This larger sample size will also provide sufficient power for the more complex 3 
site nested design. Based on our preliminary study we estimate that 20% of potential participants 
who respond to recruitment materials will not meet the inclusion criteria and an additional 25-
30% will be unable to attend the classes when scheduled. Thus, we will need to screen 320 
persons to recruit a sample of 180 participants (60 at each site). Given the number of participants 
who consent and do not complete the full data collection we will need to recruit up to 230 
persons with MS.  The number of persons with MS in the 3 communities is more than sufficient.  
 
INCLUSION/EXCLUSION CRITERIA: To participate, subjects must be diagnosed with MS, 
age 18 to 60, and capable of understanding and complying with the study protocol.  Participants 
must be able to read and write in English and have visual acuity of at least 20/70 with correction 
in order to work on the computer screen. All participants must have a clinically definite 
diagnosis of MS that is documented by their physician.  Participants must have stable disease at 
the time of entry into the study (relapse free for at least 90 days), have subjective concerns about 
their cognitive functioning (based on the Perceived Deficits Questionnaire), have home internet 
access, and be willing to participate in an 5 month study involving education/skill building, 
support and data collection. Participants may be of either gender or any ethnic/racial group. 
Subjects will be excluded if they have other medical causes of dementia or other neurological 
disorders that may impact cognition or emotions, evidence of major psychiatric disorder or if 
they have major functional limitations that preclude them from participating in the study.  
 
RECRUITMENT AND SCREENING: Participants will be recruited in a variety of ways 
including fliers in offices of physicians, targeted mailings to persons with MS on the mailing list 
of the National MS Society, contact with support groups, notices in MS newsletters and “word of 
mouth.” Letters of support for recruitment are appended. Recruitment materials will instruct 
potential participants to call the research office 800 number for additional information about the 
study. The project staff will have a script to screen potential participants for inclusion/exclusion 
criteria and will explain the study procedures and requirements to those who are eligible. The 
Perceived Deficits Questionnaire (Sullivan, Edgley & Dehoux, 1990) will be administered by 
phone and those scoring indicating they experience at least 5 problems “sometimes” or more 
often will be eligible to participate. Participants will be asked to provide the name and address of 
their physician, who will be asked to verify the diagnosis and give a medical clearance for the 
individual to participate. Recruitment will be ongoing in order to establish a pool of potential 
participants at each of the three sites. Nine cohorts of 20-22 subjects will be randomly selected 
(three times at each of three sites) during the study and subjects within the cohort will be 
randomly assigned (following baseline testing) to the treatment or comparison group. In prior 
studies, small intervention class sizes (n=10-12) enhanced self-efficacy through vicarious 
experience and modeling. 
 
Persons who do not qualify to participate in the study based on the screening criteria will be 
thanked for their interest and receive a brochure from the MS Society on cognitive strategies. 

 
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INTERVENTION: MAPSS - MS 
The overall purpose of the MAPSS-MS intervention is to help the individual acquire the highest 
level of cognitive functioning and functional independence.  This is accomplished through 
teaching the use of compensatory skills, retraining skills (the CACR component) and 
environmental/lifestyle support for cognitive functioning. The MAPSS-MS has two components: 
(a) Group sessions focused on building efficacy for use of cognitive strategies and (b) an 
innovative computer assisted cognitive rehabilitation (CACR) program. The home-based 
computer component will enable the participants to engage in intensive practice sessions without 
leaving their homes.  Translation of skills practiced to everyday issues will be a focus of the 
group sessions. 
 
Group Component The investigators’ prior work will drive the content and process aspects of the 
MAPSS-MS (Memory, Attention & Problem Solving Skills for Persons with MS) intervention - 
specifically the health promotion intervention for women with MS (R01HD35047). The intent of 
the efficacy-based wellness intervention is to engage individuals in assessing their present health 
behaviors, setting meaningful goals for change and addressing the barriers, resources and skills 
necessary to improve health behaviors and consequently quality of life. In this study, we will use 
the same process and strategies (Stuifbergen, et al., 1999; Stuifbergen et al., 2003) to assist 
participants to acquire knowledge regarding the specific MS-related cognitive impairments; 
assess and acknowledge their cognitive concerns, build the skills necessary to implement 
compensatory self-management strategies of cognitive difficulties and set goals for integrating 
new cognitive skills into their everyday lives.   
 
The group program will consist of weekly 2-hour classes over an 8 week period that present 
information, guide participants in self-assessment of cognitive problems, resources and barriers 
to cognitive functioning and enhancing self-efficacy for use of strategies to maximize cognitive 
functioning. Four major topic areas will be included in the lifestyle change classes (1) 
Identifying common cognitive problems experienced with MS (2) Compensatory Strategies to 
Maximize cognitive Skills (3) Maximizing Cognitive Health with a MS – Lifestyle adjustments 
(e.g. physical activity and energy conservation) to promote cognitive functioning (3) Adjusting 
to Changes in Cognitive Skills (4) Stress Management (controlling anxiety) and Enhancing 
Cognition. At each session, the facilitator will evaluate the participants on CACR exercises 
prescribed at the last session, troubleshoot cognitive strategies and performance difficulties, and 
prescribe the therapy exercise assignments for the upcoming week.  
 
 
 
Computer Assisted Cognitive Rehabilitation (CACR) protocol:  In response to the feedback 
obtained in preliminary studies, we will use the computer training exercises from Lumosity. The 
computer protocol for this multi-site trial follows: 
  
Computer Protocol:  The computer training methodology developed by Lumos Labs, Inc. (San 
Francisco, CA) uses an open-innovation model targeting effectiveness, designed to adapt to the 
individual user, offering novel and engaging tasks and challenges within a integrated, 
hierarchical structure.  The Lumosity program has been used in research with childhood cancer 

 
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survivors, healthy adults, and older persons with mild cognitive impairment. The Lumosity 
website (www.lumosity.com) delivers interactive programs and applications that run directly in 
standard web browsers. Users need only a computer, tablet, or smart phone to access the website 
and securely log into the program. The PIs will contract with Lumos Labs, (see letter of support) 
for use of the Lumosity program including development of a suite of specific games/training 
activities and the collection and delivery of data collected on all participants enrolled in the 
study. Research staff will register each participant on the Lumosity website using anonymous 
user ID numbers and passwords allowing participants unlimited access throughout the 8-week 
intervention period. The delivery of the computer exercises over the Internet allows the 
participant to complete the exercises from any location on any device with Internet access at any 
time. During the first group session the facilitator will demonstrate logging on and navigating the 
website before having the participants practice these skills and work through sample exercises 
using laptops connected to the internet. As each participant works through a session, the data is 
saved on the website’s servers and the participant is able to start subsequent sessions where 
he/she stopped progressing in hierarchical fashion. Each participant will be asked to complete a 
minimum of 45 minutes of training thee times per week and to keep a written log of practice 
times and dates. The researchers will monitor the skills practiced and the success at various 
levels via data reports provided via e-mail by Lumos, Labs. 
  
The facilitator will prescribe 2 consecutive weeks of practice with 4 of the Lumosity boost 
programs addressing the most common problems experienced by persons with MS.  The tasks 
are arranged so that the most basic cognitive skills (attention) are addressed first.  As the user 
progresses, the tasks become more challenging. Each boost is set up in a game like format.  The 
facilitator will be available to participants by phone and email and will contact each participant 
weekly by phone to assess for any problems using the program. 
  
Weeks 1 & 2 Attention Boost: provides training targeting visual field and focusing. Exercises 
include: Lost in Migration, a selective attention task based on the flanker test paradigm, and Bird 
Watching. 
Weeks 3 & 4 Memory Boost: provides training on skills essential to store, retain and recall 
information, events and procedures. Working memory skills are frequently used to accomplish 
everyday functioning (using a phone) and evidence suggests that working memory can be 
expanded and enhanced by practice and the use of compensation techniques. Exercises in the 
memory boost include: Spatial Speed Match, which targets working memory and is based on the 
n-back working memory paradigm, and Memory Matrix, which target spatial memory.  
Weeks 5 & 6 Flexibility Boost:  provides training on executive function/flexibility skills that play 
a major role in information processing, abstract thinking, problem solving, initiation and 
inhibition. Exercises address task switching, which is trained in the Brain Switching game, 
response inhibition, planning, and verbal fluency. 
Weeks 7 & 8 Problem Solving Boost: provides training on problem solving skills to analyze the 
facts of a situation so that accurate conclusions are made (e.g. calculating a restaurant bill). This 
boost includes logical reasoning games such as By the Rules, based on the Wisconsin Card 
Sorting Test, arithmetic, and quantitative reasoning. 
 
Comparison Group: Persons who are randomly assigned to the usual care comparison group will 
receive their usual care and a referral to “MyBrainGames”, available for free at 

 
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MultipleScerosis.com. The games (Shopping List, Word Connect and Round Up) were launched 
in 2009 by the MS Technology collaborative and challenge the player’s processing speed, 
working memory attention and task switching ability. We will not prescribe any specific amount 
of practice and participants will be asked to keep a log of any practice time– our preliminary 
studies have shown that self-report logs are significantly correlated (r=.96) to electronic 
monitoring logs. Participants will receive a weekly phone call to maintain their connection to the 
study but no other interventions. The comparison group will be asked to complete all data 
collection on the same schedule as the intervention participants and offered the printed 
intervention materials after the study.  
 
Data Analysis: Inferential analysis will be used to test the study hypotheses. Data analyses will 
be conducted using SPSS.. Neuropsychological data will be scored by the testers and verified by 
a second staff member.  Data will be entered and checked for accuracy. Internal consistency 
reliability coefficients for all self-report measures will be assessed with an expectation of alpha = 
.80 or above. Descriptive analyses will be used to obtain a profile of the sample. The groups will 
be compared at baseline on demographic and disease variables. Preliminary analysis for tests of 
assumptions such as normality, independence of errors, homogeneity of variance, and outliers 
will be conducted to determine if data transformations are necessary.  
 
Missing data are often problematic for randomized controlled trials and various strategies are 
often used to manage missing data.  We will use intention-to-treat strategies to handle missing 
data. More specifically, a “last observation carried forward” (LOCF) strategy in which missing 
data points are imputed based on the participant’s existing data.  
 
To account for cohort and city effects, multi-level analyses using SAS Proc Mixed will be 
conducted and any major effects observed will be included in subsequent analyses. A repeated 
measures (RM-ANOVA) design will be used to determine time and time by group effects on 
performance and self-report outcomes. Because of the large variability expected in a community-
residing sample of persons with MS, we will use Analysis of Covariance (ANCOVA) to control 
for the differences among participants that are not germane to assessing the magnitude of the 
difference attributable to the treatment. Therefore, ANCOVAs will be performed to determine 
the differences between the intervention group and comparison groups at T2, T3, and T4, after 
controlling for baseline scores. Separate analyses will be conducted for each outcome measure.