Clinical trial NCT02106052: Study of Exercise on Impact of Cognitive Functioning in Multiple Sclerosis Patients
Official title: The Effect of Aerobic Exercise on Cognition in Multiple Sclerosis (MS Exercise Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Keywords: cognitive function
cognitive impairment
cognitive intervention
cognitive improvement
information processing speed
exercise training program
aerobic exercise
stretching and toning
Multiple sclerosis
executive function
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Multiple Sclerosis Society
First posted: 2014-04-07
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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).
* 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.

Exclusion Criteria:

* 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.
* 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).

Primary outcomes:
measure: Composite score of the Paced Auditory Serial Addition Test-3 (PASAT-3") and the oral version of the Symbol-Digit Modalities Test (SDMT)
timeFrame: Baseline and six months after baseline.
Secondary outcomes:
measure: Delis Kaplan Executive Function System Sorting Test (DKEFS)
timeFrame: The DKEFS will be administered at six months after baseline.
measure: California Verbal Learning Test, second edition (CVLT2)
timeFrame: The CVLT2 will be administered at six months after baseline.
measure: Brief Visuospatial Memory Test Revised (BVMTR)
timeFrame: The BVMTR will be administered at six months after baseline.
measure: The Controlled Oral Word Association Test (COWAT)
timeFrame: The COWAT will be administered at six months after baseline.
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Charles H Bombardier, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.