Feasibility and Initial Efficacy of a Wheelchair Exercise-training Intervention for Persons With Multiple Sclerosis
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: The University of Texas Health Science Center, Houston

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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Feasibility and initial efficacy of a wheelchair exercise-training intervention for 
persons with multiple sclerosis 
 
NCT05888727   
 
Version Date: 06/17/2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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Protocol Template Version Jan 2018 
Adapted from NIH protocol template and ICH Guidelines 
 
 
Protocol Title: 
Feasibility and initial efficacy of a wheelchair exercise-training intervention 
for persons with multiple sclerosis 
Principal Investigator: 
Stephanie Silveira, PhD 
 
Co-Investigators: 
Robert W. Motl, PhD & Katherine Froehlich-Grobe, PhD 
 
Study Coordinator: 
Angela Piasecki 
 
Population: 
Twenty-four adults with multiple sclerosis who use wheelchairs for mobility 
in Texas 
Number of Sites: 
UTHealth Houston 
 
Study Duration: 
2 years 
 
Subject Duration: 
6 months 
 
 
General Information 
− The proposed study will examine the feasibility of a stakeholder-informed, home-based, remotely 
supported and supervised exercise training program for wheelchair users with multiple sclerosis 
(MS). The proposed exercise training program was developed in partnership with community 
members using semi-structured interviews, a community advisory board, and focus group feedback 
wherein community members provided insights to develop and refine an exercise training program 
that suit the needs and preferences of wheelchair users with MS. 
 
Background Information 
− 
Dr. Silveira recently initiated a targeted agenda for creating an exercise training intervention that 
could be assist in managing MS consequences and optimizing health and well-being among 
wheelchair users with MS (1-3). Dr. Silveira first conducted a qualitative study that explored the 
needs and preferences for exercise training among 20 wheelchair users with MS (1). Participants 
expressed interest in a home-based, remotely supported and supervised exercise program that 
included strength and aerobic training. This provided a foundation for Dr. Silveira’s NIH F32 
fellowship, guided by Prof. Motl and Prof. Froehlich-Grobe, that created the first wheelchair exercise 
training program for persons with MS. The F32 research included two phases of community- 
engaged feedback to refine and finalize the stakeholder-informed exercise training program. In 
Phase I, we convened a Community Advisory Board (CAB) of 10 persons with MS who completed 5 
weekly meetings and provided feedback on the primary components of the program: exercise 
prescription, equipment, and behavioral coaching (2). Dr. Silveira updated the intervention materials 
based on feedback received during CAB meetings and in Phase II we convened three focus groups to 
refine and verify the stakeholder perceptions regarding the appropriateness of the exercise program 

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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(3). The collective process yielded a novel wheelchair exercise training program that is ready to be 
examine for feasibility before testing within a formal clinical trial. 
 
1. Silveira SL, Richardson EV, Motl RW. Informing the design of exercise programs for persons 
with multiple sclerosis who use wheelchairs: a qualitative inquiry of perceived components. Disability 
and Rehabilitation. 2019:1-11. 
2. Silveira SL, Froehlich-Grobe K, Motl RW. Developing a community-engaged wheelchair exercise 
program for persons with MS: community advisory board formation and feedback. Disabil Rehabil Assist 
Technol. 2021 Dec 10:1-8. doi: 10.1080/17483107.2021.2010819. Epub ahead of print. PMID: 34892990; 
PMCID: PMC9215208. 
3. Silveira SL, Froehlich-Grobe K, Motl RW. Formative evaluation of an exercise training program for 
persons with multiple sclerosis who are wheelchair users. Eval Program Plann. 2023 Apr;97:102243. doi: 
10.1016/j.evalprogplan.2023.102243. Epub 2023 Jan 21. PMID: 36696872. 
 
− 
Ultimately, the this study extends Dr. Silveira’s line of research and may initiate a significant 
paradigm shift in rehabilitation research and practice by providing a critically needed home- 
based exercise training program for enhancing health, quality of life, participation, and 
independence of wheelchair user with MS. 
 
Objectives 
− 
To examine the feasibility, acceptability, and initial efficacy of a stakeholder-informed, home-based, 
remotely supported and supervised exercise training program for wheelchair users with multiple 
sclerosis (MS) compared to an attention/contact wellness control program. 
− 
Feasibility will be operationalized using ongoing assessment of as recruitment, retention, and safety. 
We hypothesize that the intervention will be feasible in terms of reaching recruitment goals (n=24; 
12 per group) within a one-year period, retaining ≥80% of those participants through the full 16- 
week study period, and safe in terms of <10% of participants reporting adverse events. We are 
defining our recruitment goals as participants who matriculate and are randomized, therefore we 
aim to consent up to 28 participants. 
− 
Acceptability will be operationalized as participant satisfaction and perceptions measured in post- 
intervention formative surveys and interviews. We hypothesize that a greater proportion of 
participants in the SPIN exercise training condition will report high satisfaction and positive 
perceptions regarding the exercise training program compared with the attention/contact wellness 
control condition. 
− 
The study will further examine changes scientific outcomes of interest (i.e., metabolic health, MS 
symptoms, and exercise behavior change) for determining effect size and sample size estimates in 
powering a larger clinical trial. We hypothesize that the SPIN exercise training intervention program 
will lead to greater improvements in metabolic health outcomes (i.e., HbA1c, cholesterol, glucose, 
and triglycerides), MS symptoms (i.e., fatigue, pain, depression, and quality of life) and exercise 
behavior compared to the attention/control wellness program. 
 
Study Design 
− 
Parallel group, randomized controlled trial 

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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− 
The study is funded for a 2 year period and participants will be involved in study procedures for 
approximately 6 months. 
− 
The primary outcome of interest is feasibility (i.e., recruitment, retention, and safety). The 
secondary outcome of interest is acceptability (i.e., participant satisfaction and perceptions). 
− 
The tertiary outcomes of interest are scientific outcomes of initial efficacy(i.e., metabolic health, MS 
symptoms, and exercise behavior). 
− 
Safety will be assessed in terms of incidence of participants reporting adverse events. 
 
Study Population 
− 
Eligibility criteria: (a) diagnosis of MS; (b) self-reported use of a wheelchair (i.e., manual wheelchair, 
power wheelchair, or scooter) ≥50% of the time; (c) age of 18 years or older; (d) relapse free for the 
past 30 days; and (e) being non-active defined as not engaging in regular physical activity 
(30 minutes accumulated per day) on more than 2 days of the week during the previous 6 months 
(i.e., not meeting current physical activity guidelines for MS). During telephone screening 
participants will complete an exercise pre-participation health screen and if participants report any 
symptoms or conditions contradictive of exercise then physician clearance will be required before 
enrollment. 
− 
Inclusion/exclusion criteria align with the samples that were engaged in our community-engaged 
foundational studies and numerous clinical trials in persons with MS and other wheelchair users 
such as spinal cord injury. 
− 
Participants will be recruited using clinic visits at UTHealth Houston and Harris Health MS clinics and 
flyers in the local community. Specifically, Dr. Lin will facilitate contact with potential participants in 
the UTHealth Houston and Harris Health clinics. 
 
Study Procedures 
− 
Interested participants will contact the Study Coordinator for a telephone screening, which includes 
a comprehensive description of the study followed by screening for inclusion criteria. Participants 
deemed eligible for the study will then be sent a consent form to review and sign using through 
REDCap. When the Study Coordinator receives the signed consent form, participants will be mailed a 
pre-test/baseline assessment packet. The pre-test assessment packet will include Actigraph GT3X+ 
accelerometer and instructions to wear the accelerometer on the non-dominant wrist for 7 days as 
well as an order for blood sample collection at a Quest Diagnostics/LabCorp location that is 
convenient for them. Participants will complete a battery of questionnaires online using REDCap. 
When the Study Coordinator receives the accelerometer and notification that a blood sample has 
been collected, participants will be randomized into the exercise training intervention condition or 
attention/contact control condition using the REDCap randomization module. Following 
randomization, participants will be mailed their condition-specific program materials as well as 
instructions for downloading Zoom. All participants will receive behavioral coaching, which is 
founded in Social Cognitive Theory (SCT) behavior change principles. Each participant will meet one- 
on-one with the same behavioral coach, the PI, weekly for the first 8 weeks of the program, and 
biweekly for the last 8 weeks (total of 12 meetings). Meetings will be recorded for auditing and 
training purposes as outlined in the consent form. The research team created 12 SCT-based, 
condition-specific newsletters that serve as the curriculum underpinning each program. Post-test 
assessment of tertiary outcomes following the 16-week intervention will mirror baseline 

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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assessments. Participants will be asked to complete an additional evaluation questionnaire to assess 
satisfaction with the program and usability of intervention components. All participants will be 
invited to complete a post-test semi-structured interview via Zoom to provide feedback on their 
experiences and suggestions for refining the program. All participants will be compensated $75 for 
completing each assessment, and an additional $25 will be provided for those who complete the 
post-test interview. 
− 
Informed Consent: Prior to completing any assessments we will review the Informed Consent 
document with each participant. The member of the research team will explain each section of this 
document and answer any questions. Participants will be asked to sign this document using REDCap 
before completing assessments and being enrolled in the study. Participants will be provided with a 
copy of the Informed Consent document for their records. 
− 
Blood Draw (Assessment 1&2): Participants will be asked to complete a blood draw at a Question 
Diagnostics location in their local community that will take approximately 30 minutes. Biological 
samples will be collected and stored at Quest Diagnostics using their standardized clinical trial 
protocol. The samples will be disposed of immediately following analyses. They will draw 4mL of 
blood using a standardized protocol. This is about 1 teaspoon of blood. The biomarkers they will 
collect include HbA1c, cholesterol, glucose, triglycerides, and insulin. 
− 
Questionnaires (Assessment 1&2): Participants will be asked to complete a battery of questionnaires 
online using REDCap at each assessment that will take 20-30 minutes. The battery of questionnaires 
includes a demographic and clinical characteristics questionnaire; the Patient Determined Disease 
Steps scale for assessing clinical disability status; the Godin Leisure Time Exercise Questionnaire; 
Fatigue Severity Scale; McGill Pain Questionnaire; Hospital Anxiety and Depression Scale; Multiple 
Sclerosis Impact Scale 29 as a quality of life measure; and the Leisure Time Physical Activity 
Questionnaire for People with Disabilities. Participants may skip any questions that make them feel 
uncomfortable. 
− 
Physical Activity Assessment (Assessment #1&2): Participants will be asked to complete a standard 
7-day accelerometery protocol using Actigraph wGT3X-bt) accelerometers 
(https://actigraphcorp.com/actigraph-wgt3x-bt/). Participants will be asked to wear the 
accelerometer on your non-dominant wrist during waking hours for 7 days. 
− 
Coaching Sessions: You will be asked to join a Zoom call with your MS Behavioral Specialist coach 
throughout the study. The calls will consist of obtaining feedback on your progress and discussing 
topics relevant to your progress in the assigned program. These calls will be recorded and kept on a 
HIPAA compliant OneDrive folder for three years for future training and random auditing purposes 
then destroyed. 
− 
Formative Evaluation (Assessment #2): Participants will be asked to complete a brief survey, online 
regarding your perceptions and experiences in the exercise training program that will take 
approximately 5-10 minutes. Participants may skip any questions that make them feel 
uncomfortable. We will also invite participants to complete an interview online, using Zoom that will 
last 20-30 minutes to provide feedback on the program they completed. 
− 
Exercise Intervention: The exercise program includes both aerobic and strength training components 
to be completed over 16-weeks. The aerobic exercise prescription is progressive and individualized. 
Each participant starts with a goal of 10 minutes aerobic training the first 2-week period (i.e., 

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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accommodation period). Participants are then assigned to one of three trajectories of progression 
over the remaining 14-week period to reach a final goal of at least two, 30-minute aerobic workouts 
per week. Fifteen resistance training exercises were developed that include body weight 
movements and use of study-provided resistance bands or wrist weights for targeting upper body, 
core muscle groups, and lower body that are adaptable for manual or power wheelchair users. 
During the proposed program, participants will choose the resistance training exercises those that 
best suit their functional capabilities and goals. The resistance training prescription begins with 1 
set of 10 repetitions of 5 exercises performed 2 days a week. Similar to the aerobic exercise 
prescription, three trajectories of progression for the resistance training will be used (i.e., sets, 
repetitions, and exercises) over the remaining 14 weeks to reach a final goal of at least 2 sets of 15 
repetitions of 10 exercises. The participant manual includes instructions on precautions and safety 
for exercise that will be reviewed with all participants during the first coaching call. Coaches will 
check-in regularly with each participant to assess safety and report any adverse events to IRB. 
− 
Wellness Intervention: The attention/contact wellness control condition will mirror the 
exercise training intervention condition, but focuses on implementing health behaviors other than 
physical activity (e.g., diet and emotional wellbeing) over 16 weeks. This program is an adapted 
version of the WellMS program from Prof. Motl’s Phase III clinical trial (NCT03490240) that Dr. 
Silveira delivered and coached during an initial postdoctoral fellowship. The program is based on SCT 
principles of behavior change and integrates wellness resources from the NMSS. The research team 
has created 12 Newsletters split into six different topics, with each topic addressed in two 
newsletters. The topics include Stress Management, Emotional Regulation, Diet, Sleep, Balance and 
Fall Risk, and Fatigue. All coaching chats and newsletters will occur with the same frequency as in 
the exercise training intervention condition. Participants will be provided with a participant manual, 
logbook, and calendar. Participants will work with their behavioral coach on goal setting specific to 
wellness behaviors. 
 
Data and Safety Monitoring 
− 
All testing will be performed by trained personnel and all equipment will be calibrated daily before 
testing. If an individual indicates discomfort or the desire to discontinue testing, tests will be 
terminated immediately. All adverse events will be reported to the UTHealth Houston IRB and 
reviewed by the investigative team. Should any of these individuals and/or the IRB identify that any 
adverse event may be related to the study protocol, testing will be suspended and the protocol will 
be amended accordingly. Adverse events will be tracked using a REDCap database for assessing the 
primary study outcomes. 
 
Statistics 
− 
The planned enrolled sample size of 28 participants (i.e., 12 per group that matriculate and are 
randomized) is justified for pilot clinical trials when there is no prior information for sample size 
estimation. 
− 
Dr. Silveira (PI) will lead the data analyses given her expertise in both quantitative and qualitative 
data analyses. Participant characteristics will be reported using means/medians and standard 
deviations/interquartile ranges for continuous variables. Categorical measures will be presented as 
counts and percentages. The analysis will use the intent-to-treat principle where patients will be 

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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analyzed in their randomization assignment. Descriptive statistics including frequencies and 
percentages will be utilized to assess the feasibility metrics for the primary and secondary outcomes 
(Hypothesis 1 & Hypothesis 2). The scientific outcomes in Hypothesis 3 (i.e., metabolic health 
outcomes, MS symptoms, and exercise behavior) will be examined using 2 time by 2 group mixed 
factor ANOVA with estimation of Cohen’s d values for effect sizes. Participant’s change in scientific 
outcomes will be further examined and compared with the ≥0.5 SD will be considered meaningful 
change based on benchmarks established in previous research. 
 
Ethics 
− 
First, following screening all participants deemed eligible for the study will then be sent a consent 
form to review and sign using through REDCap. The PI will review the consent document to ensure 
participants understand study procedures and sign the document prior to enrollment. During 
consent process the research team will emphasize the voluntary nature of all research procedures 
and assess consent at each following contact as consent is an ongoing process. 
 
Data handling and record keeping 
− 
All paper and electronic data collected from this study will be stored in a secure location on the 
UTHealth Houston campus and/or a secure UTHealth Houston server for at least three (3) years 
past the end of this research in a locked filing cabinet behind a locked door or password 
protected computer in PI’s campus office as appropriate. Research records will be labeled with a 
code and the master key linking names with codes will be maintained in a separate and secure 
location. 
− 
All participants will be assigned an identification number and all data collection, as well as data 
analyses, will be conducted with the coded non-identifiable data; there will be no link between 
the ID number and the subject’s name. All data will be kept in a locked file cabinet and only 
aggregated data will be used for presentation or publication purposes. There will not be a link 
between the identification number and participant for purposes of tracking participants over 
time. We will not maintain a link between identification number and the subject's name after 
completion of the study procedures, and there is no intention of linking data collected in the 
current project with data collected in another project. We will retain screening data for those 
who qualify and volunteer, and destroy the screening data for those who are excluded or do not 
volunteer. 
− 
Only the members of the research team listed on the IRB application will have access to the 
data. Any members of the research team who are added during the study period will be 
submitted as an amendment to the IRB prior to having access to study data or interacting with 
any human subjects. 
 
Quality control and assurance 
− 
A data and safety monitoring plan is established to ensure the safety of all participants involved in 
the study and ensure validity and integrity of the collected data. The PI will be responsible for 
execution of this plan and data collection methods using HIPAA compliant software including 
REDCap. Our laboratory currently has protocols in place for participant safety and data integrity, 
however should the need arise a report of a serious adverse event, the appropriate forms for the 
UTHealth IRB will be completed with copies provided to the funder. Participants will be asked to 

IRB NUMBER: HSC-SPH-23-0719 
IRB APPROVAL DATE: 06/17/2024 
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contact the research team via telephone or e-mail in occurrence of an adverse event or any other 
problem. Life-threatening adverse events will be reported within 24 hours and serious, but non-life- 
threatening adverse events will be reported within three days. 
 
Publication Plan 
− 
The research team will submit a protocol manuscript prior to initiating recruitment and primary 
outcomes manuscript outlining results from this study. The final results from the study will be 
presented at a national rehabilitation conference. 
− 
Aggregated data will be used for presentation or publication purposes related to reporting of results 
and subsequent grant proposals. Data will be reported such that the identity of all participants will 
be protected in all publications and presentations. 
− 
A report of the overall study findings in lay terminology will be provided to all participants following 
the completion of data analyses.