Multiple SclerosisNCT07447115
Exercise With and Without Cognitive Training
A study testing Effect of Exercise with and Without Cognitive Training on Gait in people with Multiple Sclerosis, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This proposal aims to conduct a 10-week randomized controlled trial comparing walking and resistance training with and without computerized cognitive training in older Veterans with Multiple Sclerosis, followed by 12 months of fall tracking with sensors and fall calendars. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Effect of Exercise with and Without Cognitive Training on Gait
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2027to 1 May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- US Veteran
- Diagnosis of Multiple Sclerosis
- Relapse free in the last 30 days
- Capable of standing unaided for at least 1 minute
- Expanded Disability Status Scale <6.5
- Ability to speak and understand English
Who cannot join
- Any neurological disorder other than MS
- Modified Telephone Interview for Cognitive Status <20
- Current participation in an exercise or cognitive rehabilitation study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033-4004
Joe R Nocera, PhD, 404-321-6111 ext. 6354, joenocera@emory.edu
Katherine Hsieh, PhD
About this study
Official title: The Effect of Exercise With and Without Cognitive Training on Gait in Older Veterans With Multiple Sclerosis
This proposal aims to conduct a 10-week randomized controlled trial comparing walking and resistance training with and without computerized cognitive training in older Veterans with Multiple Sclerosis, followed by 12 months of fall tracking with sensors and fall calendars. The primary objectives of this proposed CDA2 are to provide critical preliminary data on 1) the feasibility of conducting a 10-week RCT, 2) preliminary treatment effects on gait, cognition, and falls, and 3) neuroinflammatory biomarkers. Dr. Katherine Hsieh will receive hands-on training in the design and conduct of clinical trials (Dr. Hackney), mechanisms underlying physical activity, cognitive rehabilitation, and falls (Drs. Twamley, Hackney, \& Kesar), fall detection technology (Prof. Sanford), and clinical problems faced by MS participants (Dr. Backus) to achieve her long-term career goal of becoming an independent falls prevention investigator.
Read the detailed description
Significance to VA: A key aim of this proposal is to equip Dr. Katherine Hsieh with the expertise to become an independent VA investigator leading fall prevention trials for older Veterans with Multiple Sclerosis (MS). MS is a chronic, neurodegenerative disease affecting 55,00-70,000 Veterans. Over 28,000 MS cases are reported annually to the VA, and within the Paralyzed Veterans of America, 1 in 4 members have MS. Gait and cognitive impairments are the two of the most common MS symptoms and two of the most important predictors of falls, which lead to fractures, disability, and even death. Adults 55 years and older are the largest group of people living with MS, and the combination of MS symptoms and aging puts older MS Veterans at a high risk of falls. Preventing falls in older Veterans with MS is needed to improve their independence and quality of life. Innovation and Impact: This proposal seeks to utilize an innovative method of combining walking and resistance training with computerized cognitive training on fall risk outcomes. Falls are associated with slower gait speed and declines in processing speed, attention, executive function, and verbal memory. In people with MS, walking and resistance training improves gait function, and computerized cognitive training improves executive functions, processing speed, and attention. Whether combining computerized cognitive training with walking and resistance training provides additional benefits to gait, cognition, and falls remains unclear. Specific Aims: The objectives of this CDA2 proposal are to: 1) determine the feasibility of conducting a 10-week RCT comparing walking and resistance training with and without computerized cognitive training; 2) obtain estimates of intervention effects on gait, cognitive function, and prospective falls; 3) explore neuroinflammatory mechanisms underlying treatment effects. In addition, the PI has established a team of mentors (Drs. Hackney, Twamley, Sanford, Backus, and Kesar) to achieve five career development goals: 1) advance knowledge in the design and conduct of clinical trials; 2) examine mechanisms underlying physical activity, cognitive rehabilitation, and falls in older MS Veterans; 3) develop expertise in the use and implementation of fall detection technology; 4) acquire basic knowledge of clinical problems faced by people with MS; and 5) enhance professional skills including grant writing, scientific communication, and mentorship. Methodology: This trial will enroll 30 older Veterans with MS aged 55 or older randomized to 10 weeks, 3x/week of walking and resistance exercises with computerized cognitive training (n=15) or computer games (n=15). Participants will complete a battery of physical and cognitive tasks at baseline and 10-week follow-up. Following the intervention, the investigators will track falls for 12 months with an Apple watch and fall calendars. Aim 1, feasibility, will be measured with randomization, adherence, retention, and satisfaction to the 10-week trial. Aim 2 will compare gait and mobility, cognition, and future falls between intervention groups. Aim 3 will explore neuroprotective responses using brain-derived neurotrophic factor, interleukin-6, and tumor necrosis alpha to examine group differences and explore subgroup analyses.
Path to Translation/Implementation: Results of this study will provide critical preliminary data on gait, cognition, and falls to power and inform a full-scale RCT as the investigator's next Parent Merit. The investigators will also possess pilot data on biomarkers to identify responders and non-responders and target specific subgroups. Ultimately, this study aims to implement exercise and cognitive training to maximize functional independence for older Veterans with MS. In addition, leading this RCT and longitudinal study, along with taking didactic coursework and training, will help the investigator accomplish her long-term career goal to become an independent falls prevention investigator. By the conclusion of this CDA2, the investigator will possess the knowledge, skills, abilities, and preliminary data necessary to successfully compete for a Parent Merit award and launch her career as a VA falls prevention scientist.
- Conditions
- Multiple Sclerosis
- Being tested
- Effect of Exercise with and Without Cognitive Training on Gait
- Keywords
- Aging, Multiple Sclerosis, Mobility, Walking, Cognition, Rehabilitation, Falls
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Effect of Exercise with and Without Cognitive Training on GaitBehavioural
This behavioral trial aims to determine the effect of exercise with and without computerized cognitive training on gait in older Veterans with Multiple Sclerosis.
| Study group | Role | What they receive |
|---|---|---|
| Computerized Cognitive Training | Experimental | This group will complete 75 minutes of walking and resistance exercises followed by computerized cognitive training. Exercises will include treadmill walking and resistance training using bodyweight, dumbbells, and/or bands, following guidelines from the National MS Society. Progression and intensity will be individualized and gradual over time. Sessions are 3x per week for 10 weeks. After a cool-down, participants will use RehaCom for 30 minutes. Cognitive modules will progress in difficulty and tailored. Modules will target attention, executive function, logical reasoning, and memory. Receives: Behavioral: Effect of Exercise with and Without Cognitive Training on Gait |
| Active Control | Active comparator | This group will complete the same exercises as the experimental group. After their cool-down, they will use a computer for 30 minutes to play puzzle games. These games were not developed to provide cognitive rehabilitation. Games will vary each session. Receives: Behavioral: Effect of Exercise with and Without Cognitive Training on Gait |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gait speed
Participants will walk 10m at their usual and fast speeds to measure gait speed in meters/second.
Measured: Baseline & 10-week Follow-up
Exit questionnaire
Satisfaction will be examined with an exit questionnaire that uses a Likert questionnaire (5 point scale) to assay enjoyment of the intervention, willingness to continue with the intervention should participants have the opportunity and whether the participants noted improvement in aspects of well being, e.g., mood, quality of life, mental activity, physical activity, and whether the participants noted improvement in motor function, eg gait, balance, strength, etc.
Measured: 10-week Follow-up
Secondary outcomes (10)
Static Postural Control
Participants will stand for 30 seconds in challenging balance conditions. Time (in seconds) before needing to take a recovery step will be measured.
Measured: Baseline & 10-week Follow-up
Symbol Digit Modality Test
This is a test of processing speed. Participants are asked to match symbols with corresponding numbers. The score is the number of correctly matched symbols within two minutes.
Measured: Baseline & 10-week Follow-up
California Verbal Learning Test
This is a test of memory. Participants are read a list of words and asked to memorize them over the course of 5 trials. The scale ranges from 1-15 with higher scores being better.
Measured: Baseline & 10-week Follow-up
Falls efficacy scale (FES)
This is a 16-item questionnaire to measure fear of falling when doing different activities. Scale ranges from 16-64.
Measured: Baseline & 10-week Follow-up
Number of falls per month
Number of falls will be tracked via fall calendars or sensors for 12 months following the intervention.
Measured: 1 year follow up after intervention, e.g., at 15 months.
Brain-derived neurotrophic factor
BDNF will be measured in picograms/mL to determine neurotrophic effects from the intervention
Measured: Baseline & 10-week Follow-up
Tumor necrosis alpha
TNF-alpha will be measured in picograms/mL to determine inflammatory effects from the intervention
Measured: Baseline & 10-week Follow-up
Interleukin-6
IL-6 will be measured to determine inflammatory effects from the intervention
Measured: Baseline & 10-week Follow-up
Time to complete the Timed Up and Go
Begin sitting in a chair, walk 3 meters, turn around a cone, and walk back and sit in the chair. The time to complete the TUG is measured in seconds.
Measured: Baseline & 10-week Follow-up
Brief Visuospatial Memory Test
Participants are presented an image for 10 seconds and asked to reproduce the image.
Measured: Baseline & 10-week Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2026
- Study start4 Jan 2027 (estimated)
- Primary completion4 Jan 2028 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized controlled trial (RCT) in which participants will be grouped into a computerized cognitive training or active control.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Katherine Hsieh, PhD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07447115
- Sponsor's protocol ID
- RRD9-014-25M
- Other IDs
- 1IK2RD000353-01A1
- Status last verified
- Feb 2026
- First submitted
- 25 Feb 2026
- Last updated
- 3 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Exercise With and Without Cognitive Training on Gait in Older Veterans With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT07447115
- Acronym / sponsor ID
- RRD9-014-25M
- Conditions
- Multiple Sclerosis
- Keywords
- Aging, Multiple Sclerosis, Mobility, Walking, Cognition, Rehabilitation, Falls
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 4 Jan 2027 (estimated)
- Primary completion
- 4 Jan 2028 (estimated)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 3 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This proposal aims to conduct a 10-week randomized controlled trial comparing walking and resistance training with and without computerized cognitive training in older Veterans with Multiple Sclerosis, followed by 12 months of fall tracking with sensors and fall calendars. The primary objectives of this proposed CDA2 are to provide critical preliminary data on 1) the feasibility of conducting a 10-week RCT, 2) preliminary treatment effects on gait, cognition, and falls, and 3) neuroinflammatory biomarkers. Dr. Katherine Hsieh will receive hands-on training in the design and conduct of clinical trials (Dr. Hackney), mechanisms underlying physical activity, cognitive rehabilitation, and falls (Drs. Twamley, Hackney, \& Kesar), fall detection technology (Prof. Sanford), and clinical problems faced by MS participants (Dr. Backus) to achieve her long-term career goal of becoming an independent falls prevention investigator.
Detailed description
Significance to VA: A key aim of this proposal is to equip Dr. Katherine Hsieh with the expertise to become an independent VA investigator leading fall prevention trials for older Veterans with Multiple Sclerosis (MS). MS is a chronic, neurodegenerative disease affecting 55,00-70,000 Veterans. Over 28,000 MS cases are reported annually to the VA, and within the Paralyzed Veterans of America, 1 in 4 members have MS. Gait and cognitive impairments are the two of the most common MS symptoms and two of the most important predictors of falls, which lead to fractures, disability, and even death. Adults 55 years and older are the largest group of people living with MS, and the combination of MS symptoms and aging puts older MS Veterans at a high risk of falls. Preventing falls in older Veterans with MS is needed to improve their independence and quality of life. Innovation and Impact: This proposal seeks to utilize an innovative method of combining walking and resistance training with computerized cognitive training on fall risk outcomes. Falls are associated with slower gait speed and declines in processing speed, attention, executive function, and verbal memory. In people with MS, walking and resistance training improves gait function, and computerized cognitive training improves executive functions, processing speed, and attention. Whether combining computerized cognitive training with walking and resistance training provides additional benefits to gait, cognition, and falls remains unclear. Specific Aims: The objectives of this CDA2 proposal are to: 1) determine the feasibility of conducting a 10-week RCT comparing walking and resistance training with and without computerized cognitive training; 2) obtain estimates of intervention effects on gait, cognitive function, and prospective falls; 3) explore neuroinflammatory mechanisms underlying treatment effects. In addition, the PI has established a team of mentors (Drs. Hackney, Twamley, Sanford, Backus, and Kesar) to achieve five career development goals: 1) advance knowledge in the design and conduct of clinical trials; 2) examine mechanisms underlying physical activity, cognitive rehabilitation, and falls in older MS Veterans; 3) develop expertise in the use and implementation of fall detection technology; 4) acquire basic knowledge of clinical problems faced by people with MS; and 5) enhance professional skills including grant writing, scientific communication, and mentorship. Methodology: This trial will enroll 30 older Veterans with MS aged 55 or older randomized to 10 weeks, 3x/week of walking and resistance exercises with computerized cognitive training (n=15) or computer games (n=15). Participants will complete a battery of physical and cognitive tasks at baseline and 10-week follow-up. Following the intervention, the investigators will track falls for 12 months with an Apple watch and fall calendars. Aim 1, feasibility, will be measured with randomization, adherence, retention, and satisfaction to the 10-week trial. Aim 2 will compare gait and mobility, cognition, and future falls between intervention groups. Aim 3 will explore neuroprotective responses using brain-derived neurotrophic factor, interleukin-6, and tumor necrosis alpha to examine group differences and explore subgroup analyses.
Path to Translation/Implementation: Results of this study will provide critical preliminary data on gait, cognition, and falls to power and inform a full-scale RCT as the investigator's next Parent Merit. The investigators will also possess pilot data on biomarkers to identify responders and non-responders and target specific subgroups. Ultimately, this study aims to implement exercise and cognitive training to maximize functional independence for older Veterans with MS. In addition, leading this RCT and longitudinal study, along with taking didactic coursework and training, will help the investigator accomplish her long-term career goal to become an independent falls prevention investigator. By the conclusion of this CDA2, the investigator will possess the knowledge, skills, abilities, and preliminary data necessary to successfully compete for a Parent Merit award and launch her career as a VA falls prevention scientist.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized controlled trial (RCT) in which participants will be grouped into a computerized cognitive training or active control.
| Arm | Type | Receives |
|---|---|---|
| Computerized Cognitive Training | Experimental | Behavioral: Effect of Exercise with and Without Cognitive Training on GaitThis group will complete 75 minutes of walking and resistance exercises followed by computerized cognitive training. Exercises will include treadmill walking and resistance training using bodyweight, dumbbells, and/or bands, following guidelines from the National MS Society. Progression and intensity will be individualized and gradual over time. Sessions are 3x per week for 10 weeks. After a cool-down, participants will use RehaCom for 30 minutes. Cognitive modules will progress in difficulty and tailored. Modules will target attention, executive function, logical reasoning, and memory. |
| Active Control | Active comparator | Behavioral: Effect of Exercise with and Without Cognitive Training on GaitThis group will complete the same exercises as the experimental group. After their cool-down, they will use a computer for 30 minutes to play puzzle games. These games were not developed to provide cognitive rehabilitation. Games will vary each session. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- US Veteran
- Diagnosis of Multiple Sclerosis
- Relapse free in the last 30 days
- Capable of standing unaided for at least 1 minute
- Expanded Disability Status Scale <6.5
Key exclusion criteria (3 listed)
- Any neurological disorder other than MS
- Modified Telephone Interview for Cognitive Status <20
- Current participation in an exercise or cognitive rehabilitation study
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 |
|---|---|---|
| Effect of Exercise with and Without Cognitive Training on GaitThis behavioral trial aims to determine the effect of exercise with and without computerized cognitive training on gait in older Veterans with Multiple Sclerosis. | Behavioural | Active Control, Computerized Cognitive Training |
Primary outcome
Gait speed
Time frame: Baseline & 10-week Follow-up
Participants will walk 10m at their usual and fast speeds to measure gait speed in meters/second.
Exit questionnaire
Time frame: 10-week Follow-up
Satisfaction will be examined with an exit questionnaire that uses a Likert questionnaire (5 point scale) to assay enjoyment of the intervention, willingness to continue with the intervention should participants have the opportunity and whether the participants noted improvement in aspects of well being, e.g., mood, quality of life, mental activity, physical activity, and whether the participants noted improvement in motor function, eg gait, balance, strength, etc.
10 secondary outcomes
Static Postural Control
Time frame: Baseline & 10-week Follow-up
Symbol Digit Modality Test
Time frame: Baseline & 10-week Follow-up
California Verbal Learning Test
Time frame: Baseline & 10-week Follow-up
Falls efficacy scale (FES)
Time frame: Baseline & 10-week Follow-up
Number of falls per month
Time frame: 1 year follow up after intervention, e.g., at 15 months.
Brain-derived neurotrophic factor
Time frame: Baseline & 10-week Follow-up
Tumor necrosis alpha
Time frame: Baseline & 10-week Follow-up
Interleukin-6
Time frame: Baseline & 10-week Follow-up
Time to complete the Timed Up and Go
Time frame: Baseline & 10-week Follow-up
Brief Visuospatial Memory Test
Time frame: Baseline & 10-week Follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2026.
- Individual participant dataSharing planned: No
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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.
Katherine Hsieh, PhD principal investigator
Atlanta VA Medical and Rehab Center, Decatur, GA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Effect of Exercise with and Without Cognitive Training on Gait in people with Multiple Sclerosis, run by VA Office of Research and Development 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 6 inclusion and 3 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: opening soon, as of the sponsor's last update on 3 Mar 2026. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Katherine Hsieh, PhD ((404) 321-6111, khsieh5@gsu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gait speed (time frame: Baseline & 10-week Follow-up). The study lists 2 primary outcomes in all. 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 3 Mar 2026.