Effect of Computerized Cognitive Training in Persons With MS
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
Study type: Interventional

Summary: 
      Multiple sclerosis (MS) affects approximately one million people in the United States and 2.5
      million worldwide. Between one million and 1.75 million persons with MS (PwMS) worldwide are
      estimated to suffer from cognitive impairment. Unfortunately, there is currently no consensus
      on the best treatment for cognitive impairment in PwMS. The objective for this study is to
      determine if a computerized cognitive training using the BrainHQ platform can improve
      cognitive impairment in PwMS. The central hypothesis is that computerized cognitive training
      will show some improvement in cognitive impairment. The rationale for this study is to treat
      all aspects of MS, not just the physical symptoms and to help PwMS live their best life.
      Cognitive impairment is associated with higher rates of depression in PwMS and depression
      leads to medication non-adherence. This means the cognitive impairment so many PwMS are
      dealing with must be treated. Finding non-pharmacological interventions to mitigate cognitive
      declines are essential to ensure that quality of life for PwMS patients matches our ability
      to treat and mitigate their physical symptoms of MS. To obtain the overall objectives for
      this study the following specific aim will be pursued: Determine the effectiveness of
      computerized cognitive training on changes in cognitive impairment for PwMS. This will be
      accomplished by completing a randomized clinical trial with two groups: computerized
      cognitive training using BrainHQ and an active control group that will complete non-cognitive
      training programs on BrainHQ. Subjects will complete the BICAMS battery at baseline and at
      the end of their six week intervention. Subjects will be prescribed online activities through
      BrainHQ to complete 2-3 times a week for approximately 20-30 minutes each. Subjects will also
      be asked to wear an accelerometer for a week to determine if physical activity affects
      cognition. The proposed research is significant because MS is diagnosed on average at age 30,
      meaning a high percentage of the PwMS that are suffering with cognitive impairment are in
      their second, third and fourth decade when they are trying to raise a family, finish college,
      further their career and have active social lives.
    

Detailed description: 
      Kathy Healey, MS Specialist and participating personnel on this study, is one of the MS
      providers at the Nebraska Medicine MS Clinic. She helped determine the following
      inclusion/exclusion criteria as well as the protocol. She has enlisted the help of her
      colleagues to help identify eligible subjects. Patients will be identified by their MS
      provider as having cognitive impairment, having relapsing remitting MS, being between the
      ages of 19-60, not having a relapse or DMT change in the last 6 months, an EDSS of 2-5.5 and
      not undergoing cognitive therapy. The provider will then ask the patient if they are
      interested in participating in a research study and if so pass on their contact information
      to the PI. If patients meet the inclusion/exclusion criteria they will be asked to sign the
      consent form and then undergo screening to include Montreal Cognitive Assessment (MoCA), Test
      of Premorbid Functioning (ToPF), Generalized Anxiety Disorder (GAD-7), Beck Depression
      Inventory (BDI-2) and Modified Fatigue Impact Score (MFIS). While these tests are being used
      for screening purposed only and will not be administered by a certified neuropsychologist, if
      a subject answered a 2 (I would like to kill myself) or a 3 (I would kill myself if I had the
      chance) on the suicidal thoughts question of the BDI-II then Dr. Erica Schmidt would be
      contacted and the patient would be notified that the research team has to break
      confidentiality to help them with a safety plan that could include contacting their medical
      provider or sending them to the ER. Dr. Schmidt is a certified neuropsychologist and is very
      capable of making the proper decisions if a subject discloses moderate to high risk of
      suicide to ensure the safety of all subjects. If a subject answered a 1 (I have thoughts of
      killing myself but would not carry them out) then the subject would be asked to complete the
      Columbia Suicide Severity Rating Scale (C-SSRS). If the subject has more than low risk based
      on the C-SSRS then they would be excluded from the study and Dr. Schmidt would be contacted.
      All subjects that answer a one, two or three on the BDI-II will also be given a pamphlet that
      has information regarding how to make an appointment with a neuropsychologist as well as
      suicide hotline numbers.

      Once screened, those who meet the inclusion criteria based on their scores will be invited to
      continue on in the study. Eligible participants will be randomized using a block
      randomization table with group assignment: computerized cognitive training or control. Dr.
      Wichman, a biostatistician, has created a randomization chart to use to randomly assign the
      subjects. Since the PI is assigning BrainHQ programs to the participants she is unblinded and
      can use the randomization chart.

      All randomized subjects will be asked to complete the Human Activity Profile29, a physical
      activity questionnaire, and the Perceived Deficits Questionnaire32. They will also be asked
      to do a baseline Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
      battery. The BICAMS battery consists of the Symbol Digit Modalities Test (SDMT)33, the Brief
      Visuospatial Memory Test Revised (BVMT-R)34 and the California Verbal Learning Test 2nd
      edition (CVLT-II)35. The accelerometer will be given at the enrollment visit and participants
      asked to wear an accelerometer during waking hours over a 7 day period. Participants will
      return the device to researchers by mail. This visit will take approximately two hours.

      All subjects will be asked to complete the prescribed activities through BrainHQ, whether it
      is the control activities or the cognitive activities. Subjects randomized to the
      intervention group will complete prescribed cognitive training activities 3 times a week for
      20-30 minutes each time for 6 weeks. Subjects randomized to the control group will complete
      computerized control activities that are not cognitive training on BrainHQ 3 times a week for
      20-30 minutes each time for 6 weeks. The BrainHQ activities will be done on a personal
      computer or tablet. Subjects will not be provided devices as one of the inclusion criteria is
      that the patient have access to a computer and the internet. The cognitive training will
      consist of different exercises that are meant to improve processing speed, verbal memory and
      visual memory which are the domains that BICAMS tests. The control activities will be games
      similar to candy crush, connect four, gem swap and battleship. The subjects will be provided
      log in information and will not be entering any personal information on the BrainHQ
      application.

      After 6 weeks of BrainHQ programs, subjects will return for end-of-study testing that will
      take approximately one hour. They will complete the BICAMS battery again as well as fill out
      the Perceived Deficits Questionnaire.
    

Intervention name(s): BrainHQ cognitive training; BrainHQ control games
Intervention type(s): Device; Device
Intervention description(s): Posit Science's BrainHQ exercises are based on the science of "neuroplasticity," also called "brain plasticity." Brain plasticity is your brain's natural ability to remodel itself throughout life. The brain is always changing, sometimes for better, and sometimes for worse. What BrainHQ's exercises do is harness that change and direct it in ways that can enhance your overall performance and improve the quality of your life. BrainHQ exercises are grouped into six categories: Attention, Memory, Brain Speed, Intelligence, People Skills, and Navigation.; BrainHQ also offers control games for research studies. The control activities will be games similar to candy crush, connect four, gem swap and battleship.
Other intervention name(s): www.brainhq.com; www.brainhq.com
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The intervention group will complete the prescribed computerized cognitive training while the control group will complete the control games that are not cognitive training and offered through the BrainHQ website as well.
Masking: Single (Participant)
Primary purpose: Treatment