Physical Activity in Multiple Sclerosis (MS): A Novel Approach to Study Outcomes
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

Summary: 
      Physical activity and exercise interventions in multiple sclerosis (MS) have received great
      attention most recently and there exists several randomized clinical trials (RCTs) addressing
      the outcomes associated with such intervention. The majority of such interventions have
      primarily focused on directly influencing disease processes (e.g., inflammation, neurotrophic
      factors), the reduction of symptoms (e.g., fatigue, depression), improvement in physical
      functioning (e.g., gait, strength) or enhancing one's quality of life. To date, the evidence
      suggests that exercise intervention in MS holds anywhere from minimal to great promise
      depending on the outcome of interest. For some outcomes such as depression or cognition,
      findings are even less optimistic, being null, or inconsistent, at best. These inconsistent
      findings may be attributed to methodological issues such as use of subjective reports, lack
      of appropriate control group, poor compliance, and sample selection. The proposed
      investigation aims to address some of these issues by: (1) Obtaining objective measures of
      outcomes of interest (i.e., fatigue, cognition, and participation/activities of daily living
      [ADLs]) and; (2) assessing certain person-specific factors (e.g., personality) and
      intermediary factors that may be influenced by physical activity and indirectly result in
      improved outcomes (e.g., improvement in sleep and subsequent improvement in fatigue and/or
      cognition). Thus, the primary objective of the proposed investigation is to: (1) utilize
      innovative and objective measures of outcomes and; (2) obtain comprehensive assessment of
      intermediary variables (e.g., sleep) or person-specific characteristics (e.g., personality),
      which together may explain the inconsistent findings in the literature and has the following
      specific aims:

      To achieve these goals, individuals will complete a comprehensive assessment of cognition,
      person-specific factors, intermediary factors, physical fitness, and functional magnetic
      resonance imaging (fMRI) prior to and following a home based exercise intervention.
    

Detailed description: 
      PROPOSAL NARRATIVE Specific Aims Specific Aim 1: Utilize innovative and objective
      measures/techniques (i.e., brain imaging, structured clinical interviews, performance based
      assessment of functional activity) to examine the effects of physical activity on fatigue,
      cognition, and participation/activities of daily living (ADLs).

      Specific Aim 2: Obtain preliminary data to identify factors that may explain the
      inconsistencies in the literature pertaining to effects of physical activity on fatigue,
      cognition, and participation/ADLs. Specifically, intermediary factors may include sleep
      quality, depression, pain, and self-efficacy, which may be affected by the intervention and
      subsequently influence outcomes. Other potential factors that are independent of the
      intervention may include person-specific, baseline characteristics such as personality, trait
      anxiety, motivation, health beliefs and engagement in health-related behaviors, and certain
      demographics and disease variables (e.g., age).

      Procedures. Subjects will be randomly assigned to either the strength training or stretching
      group based on an a priori randomization scheme. All participants will complete pre and post
      assessments consisting of subjective and objective measures of fatigue, cognition, &
      participation/ADLs (Per Specific Aim 1). Additionally baseline physical functioning measures
      will be included.

      Fatigue Measures: Briefly, all imaging data for the study will be obtained using a 3.0 T
      Siemens Allegra scanner. The following anatomical images will be obtained: MPRAGE and
      localizer. fMRI will be performed during the performance of a cognitively fatiguing task
      (Modified SDMT [mSDMT]) during which the subject will be asked throughout the task to report
      on a scale of 0-100 how cognitively fatigued they feel "right now, at this moment." These
      ratings will then be used as an amplitude modulated regressor to determine where in the brain
      increased fatigue is associated with increased brain activity. Once this neural network is
      identified, we can compared the activation observed following the intervention.

      Intervention. The intervention will consist of a Home-based Resistance Training Intervention.
      Participants randomized to the home-based progressive resistance training (PRT) condition and
      will be provided with a training manual, an exercise log book, and resistance training
      equipment. The training manual will consist of a detailed description of the exercises to be
      performed and how to progress over 6-months. The exercise logbook will allow participants to
      provide a detailed recording of each training session. Home-based PRT equipment will consist
      of elastic bands (Thera-Band®, Hygenic Corporation, Akron, OH) and weighted vests. This
      equipment has been used successfully in supervised and home-based PRT interventions which
      have improved strength, function, and health-related outcomes in clinical populations,
      particularly older adults. Participants will be involved in an initial training session at
      Kessler Foundation (KF) to learn how to perform the exercise program including demonstration
      and practice of exercise techniques, use of training equipment, and how to monitor and record
      training progress. Four follow-up visits to KF will occur throughout the 4-month program to
      provide participants with individualized feedback and training progressions. The home-based
      PRT program is based on the American College of Sports Medicine (ACSM) guidelines for
      prescription of resistance training, as well as previous PRT programs in persons with MS.
      This prescription is further consistent with recently developed evidence-based guidelines for
      physical activity for persons with MS. The prescription will consist of 3 weekly sessions of
      1-3 sets, 8-12 repetitions of 10 exercises targeting lower body, upper body, and core muscle
      groups. The 10 exercises will include lunges, chair raises/squats, calf raises, knee flexion,
      knee extension, shoulder row, shoulder lateral raise, elbow flexion, elbow extension, and
      abdominal curls. The intensity of the training program will be prescribed based on the type
      or color of elastic band used and the amount of weight in the weighted vest, and is based on
      previous studies using these modalities.Five colors of elastic bands will be used which vary
      in level of resistance or difficulty (i.e., yellow < red < green < blue < black).
      Participants will begin with the yellow band and progress following the described color band
      progression. The amount of weight added to the weighted vest will be determined as a percent
      of each individual's body weight. The initial weight in the vest will be set as 0.5% of body
      weight. Vest weight progression will occur by adding 0.5 to 1.5% of body weight every 2 weeks
      for the first 12 weeks of the program. During the second half of the program, vest weight
      progression will occur by adding 0.05 to 1.0% of body weight every 2 weeks. At each follow-up
      training session, body weight will be re-assessed to ensure accurate training progression.
      Other progressions throughout the program will include increasing the number of sets and
      repetitions, and increasing the level of difficulty of the exercises (e.g., changing exercise
      position from sitting to standing). Individualized feedback and progress with the program
      will be provided during one-on-one phone chat sessions. This will provide participants with
      the opportunity to modify and adapt their goals as they progress through the program with the
      ultimate goal of developing the skills necessary to independently monitor and change their
      behavior. The behavioral content will be delivered through text-based materials and
      one-on-one phone chat sessions with a member of the research team not involved in outcome
      assessments. Text-based materials will be provided at the initial training session including
      the training manual, exercise log book, and information on self-monitoring and setting goals
      for the PRT program.

      Comparison Group. Individuals in the stretching condition will participate in a four month
      home-based stretching program developed by the National Multiple Sclerosis Society (NMSS).
      They will be provided text-based materials and asked to provide a weekly log book. In efforts
      to equate the attention received, individuals will come to KF at the same frequency as those
      receiving the PRT intervention and will also engage in the same number of chat sessions to
      assess their adherence to the program.
    

Intervention name(s): Strength training; Stretching
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Participants will engage in a home-based strength training program.; Participants will engage in a home-based stretching training program
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Exercise