Exercise & Brain Health in MS
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis
Study type: Interventional

Summary: 
      The purpose of this study is to learn more about multiple sclerosis (MS). The investigators
      are studying whether aerobic exercise is better than a stretching program at improving brain
      health in people with MS. We want to learn:

        1. If it is safe and practical for people with MS to participate in an aerobic exercise
           program with the goal of increasing cardiac fitness. Cardiac fitness is measured with
           exercise stress tests at the beginning and end of the study.

        2. If aerobic exercise improves brain metabolism, a reflection of brain health, more than
           stretching. Brain metabolism is measured by MRIs at the beginning and end of the study.

      There is a 50% chance of being in the aerobic exercise or the stretching program.

      There are between 8 and 36 visits to OHSU, depending on the intervention group. The total
      duration of the study is at most 21 weeks.
    

Detailed description: 
      Multiple sclerosis (MS) is a disease of brain, spinal cord and optic nerves. Current MS
      therapies reduce the frequency and severity of MS flare-ups, but do not help MS in later
      stages of disease characterized by slow progression of disability. One obstacle to developing
      therapies for progressive aspects of disease is a lack of ability to measure progression and
      brain repair.

      A new MRI technique developed by Bill Rooney, PhD, (co-investigator, OHSU Advanced Imaging
      Resource Center) looks at brain health by measuring levels of phosphorous. Phosphorous levels
      are thought to reflect energy stores produced by brain cells. The healthier the brain, the
      greater the energy stores seen as higher the levels of phosphorous on imaging. Dr. Rooney has
      shown decreased levels of phosphorous on brain MRIs from people with MS. We propose that
      therapies that boost brain cell health will lead to an increase in brain cell energy stores
      and be reflected by an increase in phosphorous levels on MRI spectroscopy.

      In order to test whether improvements in brain energy stores can be seen as increased
      phosphorous levels, we will use a therapy known to improve energy stores in muscles and see
      if it also does so in the brain. We measure how much aerobic exercise increases energy stores
      in muscles by measuring oxygen utilization during an exercise stress test. Therefore in this
      study, we will see if the aerobic exercise that improves muscle energy stores (seen as an
      increase in oxygen utilization) corresponds to an increase in brain energy stores (seen as an
      increase in phosphorous levels).

      Specific Aim 1. To determine if it is safe and feasible to conduct an aerobic exercise
      intervention in MS patients to achieve an increase in oxygen utilization by 5-15%.

      Hypothesis: An MS cohort undergoing a structured aerobic exercise program will increase their
      aerobic capacity by 5-15% as measured by oxygen utilization testing and not experience
      adverse events related to the exercise program.

      Specific Aim 2. To determine if brain phosphorous levels by MR spectroscopy before and after
      an aerobic exercise intervention increases in association with increases in oxygen
      utilization.

      Hypothesis: Aerobic exercise will increase energy stores in both muscles and the brain. Body
      energy stores will be measured by oxygen utilization testing and brain energy stores by
      phosphorous levels. We expect that increases in by oxygen utilization after a structured
      exercise program will be associated with increases in phosphorous levels. We do not expect
      increases in either by oxygen utilization or phosphorous levels in an MS cohort matched for
      sex and baseline aerobic capacity that participates in a non-aerobic stretching program of
      the same duration and intensity.

      Outcome measures: The primary outcome is change in brain phosphorous levels by MRI
      spectroscopy. The secondary outcomes are changes in oxygen utilization levels, walking and
      balance tests, and changes in cognitive function and energy levels.

      Methods: Participants will be enrolled over a 1 year period. Potential subjects will undergo
      a baseline exercise stress test for oxygen utilization. Participants matched by sex and
      baseline oxygen utilization level will undergo a baseline MRI spectroscopy study and then be
      randomly assigned to either an aerobic exercise program or a self-guided stretching program.
      The aerobic exercise program consists of supervised 30 minute sessions of either treadmill or
      stationary bicycle exercise, 4 days per week for 8 weeks. The self-guided home stretching
      program consists of 30 minute sessions, 4 days a week for 8 weeks with supervised sessions
      occurring every 2 weeks. All participants will undergo a final exercise stress test and MRI
      spectroscopy. Only participants who are matched and assigned to either exercise or stretching
      groups will undergo MRI testing and receive payment for participation.
    

Intervention name(s): Aerobic Exercise; Stretching; Aerobic Exercise- Healthy Subjects
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): Each subject will exercise 30 minutes per session, four times per week for 8 weeks at the OHSU Human Performance Laboratory (HPL). Choice of treadmill or cycle ergometer for each subject will be made based on subject ability by the HPL staff and maintained for the duration of the study. Exercise intensity will be determined by training heart rate to be provided to the subject based on the anaerobic threshold during initial stress test. Throughout the study, patients will be instructed not to alter their diet or baseline level of activity.; Each subject will follow a self-guided stretching program 30 minutes per session, four times per week for 8 weeks. The initial session will be supervised at the OHSU Human Performance Laboratory (HPL) and additional supervised sessions will occur every 2 weeks to support compliance with the program. Throughout the study patients will be instructed not to alter their diet or baseline level of activity.; Each subject will follow a self-guided aerobic exercise program 30 minutes per session, four times per week for 8 weeks. The initial session will be supervised at the OHSU Human Performance Laboratory (HPL) and additional supervised sessions will occur every 2 weeks to support compliance with the program. Throughout the study patients will be instructed not to alter their diet or baseline level of activity.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Exercise; MRI