Multiple SclerosisNCT02106052
Study of Exercise on Impact of Cognitive Functioning in Multiple Sclerosis Patients
A study testing Aerobic exercise and Stretching and toning exercise in people with Multiple Sclerosis, run by University of Washington at 1 site in United States.
Trial summary
Cognitive impairment affects roughly 50% of people with multiple sclerosis (MS). There are currently no satisfactory medical treatments for cognitive impairments related to MS and alternative forms of treatment are needed. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Aerobic exercise and Stretching and toning exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to May 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- English as primary language.
- At least 9th grade education.
- Physician confirmed, clinically definite MS diagnosis as defined by the revised McDonald criteria.
- All MS subtypes will be included.
- MS diagnosis at least 6 months prior.
- Impaired speed of information processing and working memory based on either the PASAT-3" or the SDMT (i.e. z <-1.5 controlling for age, education and sex).
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- Physician clearance to engage in aerobic exercise training.
- Able to walk at least 100 meters without assistance (Expanded Disability Severity Scale score equivalent 0-5.5).
- Currently exercising less than public health recommendations (engaging in less than 30 minutes of structured physical activity less than 3 times per week during the past 6 months).
- Willingness not to undertake additional structured exercise or leisure time physical activity during the 6-month trial.
- Willing and able to participate in either exercise training program 3 days per week for 6 months at a YMCA in the Greater Seattle Area.
Who cannot join
- Near visual acuity with correction 20/70 or worse.
- Contra-indications for exercise training based on American Heart Association (AHA)/ACSM screening criteria using PAR-Q.
- Using any medication known to have adverse effects on motor or cognitive function, including monoamine oxidase inhibitors, sympathomimetics, antipsychotic agents, modafinil, oxybutynin, tricyclic antidepressants, cholinesterase inhibitors and anticonvulsants other than gabapentin and pregabalin. The following are permitted if the patient has been on a stable dose for at least 6 weeks: short acting benzodiazepines (qhs administration only), anti-spasmodics, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.
- Received steroids in last 30 days.
- Relapse in the last 90 days.
- Undergone neuropsychological testing within the past 6-months.
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- Neurological/psychological disease other than MS that may impact cognitive status, e.g. Alzheimer's disease, Parkinson's, stroke, TIA, Vascular Dementia, Huntington's, traumatic brain injury or chronic CNS infection.
- Dementia based on a definition validated in people with MS using the MACFIMS (> 2 SD below the mean on at least one memory test and > 2 SD below the mean on at least one neuropsychological test in another domain).
- Prior history of diagnosis or treatment for serious mental illness (obsessive-compulsive disorder, schizophrenia, other psychotic disorders, bipolar disorder).
- Diagnosis of major depressive disorder prior to the diagnosis of MS.
- History of significant developmental or learning disorder that may affect participation and confound interpretation of study results.
- Current major depressive disorder.
- Current alcohol or other drug abuse as measured by the WHO Alcohol, Smoking and Substance Involvement Screening Test (WHO ASSIST V3.0).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Aerobic Exercise on Cognition in Multiple Sclerosis (MS Exercise Study)
Cognitive impairment affects roughly 50% of people with multiple sclerosis (MS). There are currently no satisfactory medical treatments for cognitive impairments related to MS and alternative forms of treatment are needed. Exercise training can improve cognition in older adults and people with mild cognitive impairments, including those with early Alzheimer's disease. Therefore, the investigators plan to conduct the first definitive study that will test the theory that moderately intense aerobic exercise can improve cognition in people with MS-related impairment - specifically in information processing speed - more so than non-aerobic stretching and toning (both forms of exercise will be performed 3 days per week for 6 months).
Primary study hypothesis: The investigators hypothesize greater improvement in speed of information processing from pre- to post-treatment in the aerobic exercise group compared to the stretching and toning group (attention control).
Read more
Secondary study hypothesis: The investigators hypothesize greater improvement in other cognitive domains and patient reported outcomes from pre- to post-testing in the aerobic exercise group compared to the stretching and toning group (attention control).
The investigators plan to recruit 125 adults with MS who can walk without assistance and without rest for at least 100 meters and have mild weaknesses in information processing speed. The investigators will randomly assign 50% of participants to an aerobic exercise program and 50% to a non-aerobic exercise program (stretching and toning). In order to determine whether the intervention is successful, the investigators will compare cognitive functioning in both exercise groups before the exercise-training program, at the end of the 6-month training program and three months after the end of the training program. If our study findings support our hypotheses, this would be a relatively no-barriers treatment option to further explore for other people with MS including people with greater and lesser baseline disability.
- Conditions
- Multiple Sclerosis
- Being tested
- Aerobic exercise, Stretching and toning exercise
- Keywords
- cognitive function, cognitive impairment, cognitive intervention, cognitive improvement, information processing speed, exercise training program, aerobic exercise, stretching and toning, Multiple sclerosis, executive function
- Medical subject headings
- Multiple Sclerosis, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic exerciseOther
The aerobic exercise condition is a graduated program of supervised aerobic exercise up to one hour per day, three days per week, and lasting 6 months. The structured exercise portion of the sessions will initially last for 15-20 minutes at 40-50% heart rate reserve (HRR) and progressively increase up to 35-40 minutes in duration at 65-75% HRR during the last month of the program. The program will focus on large, dynamic movements of the lower extremities (e.g. leg cycling ergometry). There may be some individual variation in adaptations that dictate the exact characteristics of the program.
Stretching and toning exerciseOther
The stretching and toning condition is a supervised stretching program with Therabands up to one hour per day, three days per week, and lasting 6 months. The stretching exercises will be based on a manual published by the National Multiple Sclerosis Society (NMSS) that has been standardized, manualized for reproducibility, and the investigators will progressively include more exercises and sets with Therabands for resistance over the course of the 6-month period.
| Study group | Role | What they receive |
|---|---|---|
| Aerobic exercise | Active comparator | Not described Receives: Other: Aerobic exercise |
| Stretching and toning exercise | Other | Not described Receives: Other: Stretching and toning exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite score of the Paced Auditory Serial Addition Test-3 (PASAT-3") and the oral version of the Symbol-Digit Modalities Test (SDMT)
The PASAT-3" is an auditory processing speed measure in which patients are exposed to single digit numbers voiced every three seconds. After each number presentation, the patient's task is to respond with the sum of the last two digits presented. There are 60 stimuli. The main score is the number of correct responses. The SDMT will be used to measure visual processing speed. This test presents a stimulus key of numbers paired with abstract symbols at the top of a page. Patients scan the page below the key that has rows of symbols without the paired numbers. The task is to generate the associated numbers orally as fast as possible.
Measured: Baseline and six months after baseline.
Secondary outcomes (4)
Delis Kaplan Executive Function System Sorting Test (DKEFS)
The DKEFS will be used to assess higher executive function. Six cards are presented which can be sorted in at least eight different ways (e.g., card color, card shape, semantic association). Patients are allowed four minutes with each deck to sort the cards in as many ways possible. The dependent variables are the total number of correct sorts and the total verbal description score among the two decks.
Measured: The DKEFS will be administered at six months after baseline.
California Verbal Learning Test, second edition (CVLT2)
The CVLT2 will be used to evaluate multi-trial learning and long-term recall for verbal information. The test presents a list of 16 words over 5 learning trials using a selective reminding procedure. Patients are asked to recall as many words as they can after each trial followed by a delay interval, after which they are again asked to recall as many words from the list as possible. The investigators will use the total number of words recalled during the initial learning trials and the number of words recalled after the delay interval as outcomes for this study.
Measured: The CVLT2 will be administered at six months after baseline.
Brief Visuospatial Memory Test Revised (BVMTR)
The BVMTR will be used to assess visuospatial memory. The test presents a matrix of six visual designs over three learning trials, each time for 10 seconds. After each trial the patient is asked to reproduce the figures in their correct location. After a 20-25 minute delay, patients are again asked to redraw the designs. The investigators will use the total score over the three learning trials and the total number recalled after the 20-25 minute delay as outcomes.
Measured: The BVMTR will be administered at six months after baseline.
The Controlled Oral Word Association Test (COWAT)
The COWAT will be used to assess verbal fluency. The test requires patients to generate words orally that begin with a given letter of the alphabet. The outcome is the total number of correct words over the three trials.
Measured: The COWAT will be administered at six months after baseline.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2014 (estimated)
- Study startMar 2014
- Primary completionMay 2020 (estimated)
- Study completionMay 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Responsible party
- Principal investigator, Charles Bombardier, University of Washington
- Investigators
- Charles H Bombardier, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106052
- Sponsor's protocol ID
- 46598
- Status last verified
- Apr 2020
- First submitted
- 14 Mar 2014
- Last updated
- 5 May 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Bombardier CH, Motl RW, Benedict RHB, Temkin N, Qian P, Alexander K, Evans A, Thomas A, Toms K, Carey CM, Kraft GH. Exercise training and cognition in multiple sclerosis: The GET Smart trial protocol. Contemp Clin Trials. 2021 May;104:106331. doi: 10.1016/j.cct.2021.106331. Epub 2021 Feb 27.
PubMed 33652128
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Aerobic Exercise on Cognition in Multiple Sclerosis (MS Exercise Study)
- ClinicalTrials.gov ID
- NCT02106052
- Acronym / sponsor ID
- 46598
- Conditions
- Multiple Sclerosis
- Keywords
- cognitive function, cognitive impairment, cognitive intervention, cognitive improvement, information processing speed, exercise training program, aerobic exercise, stretching and toning
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 117 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Study start
- Mar 2014 (actual)
- Primary completion
- May 2020 (estimated)
- Study completion
- May 2020 (estimated)
- First posted
- 7 Apr 2014 (estimated)
- 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.
Cognitive impairment affects roughly 50% of people with multiple sclerosis (MS). There are currently no satisfactory medical treatments for cognitive impairments related to MS and alternative forms of treatment are needed. Exercise training can improve cognition in older adults and people with mild cognitive impairments, including those with early Alzheimer's disease. Therefore, the investigators plan to conduct the first definitive study that will test the theory that moderately intense aerobic exercise can improve cognition in people with MS-related impairment - specifically in information processing speed - more so than non-aerobic stretching and toning (both forms of exercise will be performed 3 days per week for 6 months).
Primary study hypothesis: The investigators hypothesize greater improvement in speed of information processing from pre- to post-treatment in the aerobic exercise group compared to the stretching and toning group (attention control).
Secondary study hypothesis: The investigators hypothesize greater improvement in other cognitive domains and patient reported outcomes from pre- to post-testing in the aerobic exercise group compared to the stretching and toning group (attention control).
The investigators plan to recruit 125 adults with MS who can walk without assistance and without rest for at least 100 meters and have mild weaknesses in information processing speed. The investigators will randomly assign 50% of participants to an aerobic exercise program and 50% to a non-aerobic exercise program (stretching and toning). In order to determine whether the intervention is successful, the investigators will compare cognitive functioning in both exercise groups before the exercise-training program, at the end of the 6-month training program and three months after the end of the training program. If our study findings support our hypotheses, this would be a relatively no-barriers treatment option to further explore for other people with MS including people with greater and lesser baseline disability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aerobic exercise | Active comparator | Other: Aerobic exercise |
| Stretching and toning exercise | Other | Other: Stretching and toning exercise |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- English as primary language.
- At least 9th grade education.
- Physician confirmed, clinically definite MS diagnosis as defined by the revised McDonald criteria.
- All MS subtypes will be included.
- MS diagnosis at least 6 months prior.
Key exclusion criteria (13 listed)
- Near visual acuity with correction 20/70 or worse.
- Contra-indications for exercise training based on American Heart Association (AHA)/ACSM screening criteria using PAR-Q.
- Using any medication known to have adverse effects on motor or cognitive function, including monoamine oxidase inhibitors, sympathomimetics, antipsychotic agents, modafinil, oxybutynin, tricyclic antidepressants, cholinesterase inhibitors and anticonvulsants other than gabapentin and pregabalin. The following are permitted if the patient has been on a stable dose for at least 6 weeks: short acting benzodiazepines (qhs administration only), anti-spasmodics, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.
- Received steroids in last 30 days.
- Relapse in the last 90 days.
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 |
|---|---|---|
| Aerobic exerciseThe aerobic exercise condition is a graduated program of supervised aerobic exercise up to one hour per day, three days per week, and lasting 6 months. The structured exercise portion of the sessions will initially last for 15-20 minutes at 40-50% heart rate reserve (HRR) and progressively increase up to 35-40 minutes in duration at 65-75% HRR during the last month of the program. The program will focus on large, dynamic movements of the lower extremities (e.g. leg cycling ergometry). There may be some individual variation in adaptations that dictate the exact characteristics of the program. | Other | Aerobic exercise |
| Stretching and toning exerciseThe stretching and toning condition is a supervised stretching program with Therabands up to one hour per day, three days per week, and lasting 6 months. The stretching exercises will be based on a manual published by the National Multiple Sclerosis Society (NMSS) that has been standardized, manualized for reproducibility, and the investigators will progressively include more exercises and sets with Therabands for resistance over the course of the 6-month period. | Other | Stretching and toning exercise |
Primary outcome
Composite score of the Paced Auditory Serial Addition Test-3 (PASAT-3") and the oral version of the Symbol-Digit Modalities Test (SDMT)
Time frame: Baseline and six months after baseline.
The PASAT-3" is an auditory processing speed measure in which patients are exposed to single digit numbers voiced every three seconds. After each number presentation, the patient's task is to respond with the sum of the last two digits presented. There are 60 stimuli. The main score is the number of correct responses. The SDMT will be used to measure visual processing speed. This test presents a stimulus key of numbers paired with abstract symbols at the top of a page. Patients scan the page below the key that has rows of symbols without the paired numbers. The task is to generate the associated numbers orally as fast as possible.
4 secondary outcomes
Delis Kaplan Executive Function System Sorting Test (DKEFS)
Time frame: The DKEFS will be administered at six months after baseline.
California Verbal Learning Test, second edition (CVLT2)
Time frame: The CVLT2 will be administered at six months after baseline.
Brief Visuospatial Memory Test Revised (BVMTR)
Time frame: The BVMTR will be administered at six months after baseline.
The Controlled Oral Word Association Test (COWAT)
Time frame: The COWAT will be administered at six months after baseline.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2020.
- Derived from this study: PubMed 33652128Bombardier CH, Motl RW, Benedict RHB, Temkin N, Qian P, Alexander K, Evans A, Thomas A, Toms K, Carey CM, Kraft GH. Exercise training and cognition in multiple sclerosis: The GET Smart trial protocol. Contemp Clin Trials. 2021 May;104:106331. doi: 10.1016/j.cct.2021.106331. Epub 2021 Feb 27.
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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.
Charles H Bombardier, PhD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aerobic exercise and Stretching and toning exercise in people with Multiple Sclerosis, run by University of Washington 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 11 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 5 May 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. 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?
Results are not available in the source record.
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?
Composite score of the Paced Auditory Serial Addition Test-3 (PASAT-3") and the oral version of the Symbol-Digit Modalities Test (SDMT) (time frame: Baseline and six months after baseline.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02106052, which also lists 1 linked publication.
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 5 May 2020; AzTrials last refreshed its copy on 30 Oct 2026.