Improving Cognition in People With Progressive Multiple Sclerosis Using Aerobic Exercise and Cognitive Rehabilitation
Condition: Multiple Sclerosis, Primary Progressive; Cognitive Impairment
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
Study type: Interventional

Summary: 
      Given that up to 70% of people with secondary progressive MS are cognitively impaired, the
      search for effective treatments is considered a priority by people living with the disease.
      This proposal will address the effectiveness of cognitive rehabilitation (CR) and exercise,
      either alone, or in combination in this regard. A team of MS researchers has been assembled
      from the USA, Canada, the United Kingdom, Italy, Denmark, Germany and Belgium for this. A
      total of 360 people with progressive MS will make up the sample. Brain MRIs will be
      undertaken in a third of the sample before and after the 12 weeks of treatment to document
      the functional changes that are expected to occur with symptom improvement.
    

Detailed description: 
      Aim: The broad aim of this proposal is to evaluate a multidisciplinary and multi-modal
      approach to rehabilitation in people with progressive MS. Cognitive rehabilitation and
      aerobic exercise will be evaluated individually and in combinations to address cognitive
      dysfunction as the primary outcome variable.

      Over 20 years have passed since the introduction of the first disease modifying treatment,
      interferon beta-1betaseron (b), for multiple sclerosis (MS).Since then 13 treatments have
      been approved and made it onto the market. All are for relapsing-remitting disease (RRMS),
      apart from mitoxantrone which is limited to progressive disease with relapses,
      Interferon-beta-1b, which is for secondary progressive disease (SPMS), but does not delay
      disability progression and Ocrelizumab for primary progressive MS only. Thus, for a sizeable
      proportion of people with MS there is no therapeutic option to slow progression. This raises
      the question, how are patients with primary and secondary progressive MS (PPMS and SPMS) to
      be helped? While research is underway to find a medication that holds promise of halting
      further deterioration in a disease that has already entered a progressive stage, patients and
      their clinicians are left with basically symptomatic treatments.

      Hypothesis: The investigators hypothesize that CR and aerobic exercise are effective
      treatments for cognitive impairment (processing speed deficits) in people with progressive
      MS. In particular a combination of these two treatment given twice weekly over 12 weeks is
      more effective than each individual treatment given alone or as sham. The investigators
      further hypothesize that improvements in processing speed will be matched on functional MRI
      (fMRI) by enhanced neural activity in networks associated with information processing speed.
    

Intervention name(s): Cognitive Rehabilitation; Sham Exercise; Sham Cognitive Rehabilitation; Aerobic Exercise
Intervention type(s): Other; Other; Other; Other
Intervention description(s): RehaCom software
Information processing speed and attention modules; Sets of balance and stretching exercises; Kompozer software
24 session module consisting of basic internet searches; Recumbent NuStep Bike
Aerobic cycling
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: We propose undertaking a randomized, blinded, sham controlled clinical trial investigating the effectiveness of CR and exercise, either singly or in combination, in treating cognitive dysfunction in people with progressive MS. Subjects will be randomly assigned to one of four groups: CR plus exercise; CR plus passive exercise; passive CR plus exercise and passive CR plus passive exercise. Subjects will receive one of these four treatments for 12 weeks, twice a week. One in three subjects will undergo structural and functional MRI to investigate how the brain responds to the two interventions.
Masking: Double (Participant, Investigator)
Primary purpose: Other