Study of Exercise on Impact of Cognitive Functioning in Multiple Sclerosis Patients

NCT ID: NCT02106052

Last Updated: 2020-05-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2020-05-31

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Aerobic exercise

Group Type: ACTIVE_COMPARATOR

Aerobic exercise

Intervention Type: OTHER

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 exercise

Group Type: OTHER

Stretching and toning exercise

Intervention Type: OTHER

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.

Interventions

Aerobic exercise

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.

Intervention Type: OTHER

Stretching and toning exercise

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.

Intervention Type: OTHER

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Multiple Sclerosis Society

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Charles Bombardier

Professor, Department of Rehabilitation Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles H Bombardier, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33652128 (View on PubMed)

Other Identifiers

46598

Identifier Type: -

Identifier Source: org_study_id