Validation Study: Mobile DSST on Cognition in Adults With MDD
Condition: Major Depressive Episode
Study type: Interventional

Summary: 
      Objectives The primary objective of this study is to determine the convergent validity of the
      mobile DSST application with the pencil and paper version of the DSST.

      Design and Outcomes This study will be performed by the Brain and Cognition Discovery
      Foundation (BCDF). The BCDF is an organization based in Toronto, Ontario, Canada led by Dr.
      Roger S. McIntyre. Membership of the BCDF has developed and validated rating scales and
      metrics for adults with mood disorders for over 10 years. A member of the BCDF provides
      diagnoses and treatment for adults (age 18-65) with mood disorders and provides clinical care
      to the largest catchment area in Canada. The BCDF conducts clinical research according to the
      International Conference on Harmonization, Declaration of Helsinki, and Good Clinical
      Practice (GCP) guidelines. The study will be approved by the community Research Ethics Board.

      Thirty adults (18-65) with DSM-5 MDD will be enrolled at the BCDF Toronto, Ontario. All
      subjects will have their diagnosis ascertained clinically and confirmed by Mini International
      Neuropsychiatric Interview Version 5.0 (M.I.N.I.).

      At baseline, data will be collected from all participants and will include demographics,
      comorbidities, medication history and concurrent medications. All subjects will be assessed
      symptomatically with the Montgomery and Asberg Depression Rating Scale (MADRS) as well as the
      Hamilton Anxiety Rating Scale (HAM-A), Snaith Hamilton Pleasure Scale (SHAPS) for anhedonia,
      as well as the paper and pencil version of the DSST at baseline and end of study (Day 7).

      The DSST has been normed on the sex, age and gender. These norms will be used as reference.
      All subjects will complete the pencil and paper version of the DSST and complete the mobile
      app-based version of the DSST.

      Sample Size and Population This is a small validation study of 30 subjects. Subjects
      diagnosed with major depressive disorder will be eligible for participation in this study.
    

Detailed description: 
      Primary Objective The primary objective of this study is to determine the convergent validity
      of the mobile DSST application with the pencil version of the DSST.

      Secondary Objectives To determine whether a correlation exists between the digitalized DSST
      performance and depression symptoms severity.

      To determine patient satisfaction with the digitalized version of the DSST as measured by a
      satisfaction Likert scale.

      Background Health-related information and communication technology solutions that utilize
      mobile phones, known as mobile health applications (apps), have the potential to expand
      health interventions beyond face-to-face contacts of traditional healthcare. For the
      healthcare provider, mobile apps can offer low cost and easily scalable interventions to
      monitor and improve services to patient populations that are difficult to retain in
      treatment, potentially leading to more sensitive measurement of cognition, mood and may
      promote better health. Uptake of health-related mobile apps has increased in recent years as
      technology barriers such as access, knowledge, and product usability have improved, reducing
      obstacles for 'digitally excluded' subpopulations (e.g., poor, rural, and older). Consensus
      exists that the availability of a mobile phone application-based cognitive measure would be
      more user friendly, aligned with busy office practice and would be more likely to be adopted
      by end users. Patients with depression and their treating provider may benefit from the use
      of a mobile health app to assist in disease self-management. This validation study will
      assess the convergent validity of the mobile DSST application with the pencil version of the
      DSST. Correlations between performance on app-based version of the DSST and paper-based
      version of DSST will be measured.

      Study Rationale MDD is a serious public health concern worldwide with ample documentation
      demonstrating that MDD is one of the leading contributors to the global burden of disease and
      is currently the leading cause of disability worldwide. Moreover, the economic burden of MDD
      is estimated to total $210.5 billion with approximately 50% of the cost being attributable to
      impairment in role function (e.g., workplace performance: presenteeism, absenteeism, and
      short-/long-term disability). Accumulating evidence suggests that the treatment and
      resolution of mood symptoms among individuals with MDD is insufficient in facilitating full
      functional recovery among individuals affected by MDD wherein a highly reproduced observation
      is that impairments in cognitive function remain persistent, pervasive, and progressive
      during the "remitted" state. The foregoing portrait of MDD as a multidimensional syndrome
      associated with cognitive impairment and differential functional implications, provides the
      impetus for evaluating the disparate domains commonly affected in this clinical population
      using valid and reliable measures/assessments capable of providing actionable information in
      the treatment and management of patients.

      Hitherto, clinical awareness surrounding the pertinence of cognitive impairment in MDD and
      its impact on functional recovery has been limited with no "gold standard tool(s)" to detect
      cognitive impairments in adults with MDD. Moreover, although several screening/measurement
      instruments are currently available that have demonstrated sensitivity to cognitive
      impairments in select cognitive domains, only one tool, to the authors' knowledge, has been
      developed primarily to evaluate the four principal cognitive domains affected in adults
      (18-65) with MDD (i.e., executive function, learning and memory, processing speed, as well as
      attention/concentration) using a composite score.

      Available evidence, and evidence-based guidelines for MDD now recommend systematic assessment
      and measurement of cognitive dysfunction in adults with MDD. A barrier to implementation of
      the foregoing recommendation is the availability of a user-friendly point of care patient
      administered potentially interoperable engaging measure of cognitive function with in MDD.

      Although many screening instruments and neurocognitive batteries are available to assess
      cognition, most are not routinely available in clinical ecosystems and/or are costly, require
      professional interpretation and/or too cumbersome for busy office practice.

      STUDY DESIGN This study will be performed by the BCDF. The BCDF is an organization based in
      Toronto, Ontario, Canada led by Dr. Roger S. McIntyre. Membership of the BCDF has developed
      and validated rating scales and metrics for adults with mood disorders for over 10 years. A
      member of the BCDF provides diagnoses and treatment for adults (age 18-65) with mood
      disorders and provides clinical care to the largest catchment area in Canada. The BCDF
      conducts clinical research according to the International Conference on Harmonization,
      Declaration of Helsinki, and GCP guidelines. The study will be approved by the community
      Research Ethics Board.

      Thirty adults (18-65) with DSM-5 MDD will be enrolled at the BCDF Toronto, Ontario. All
      subjects will have their diagnosis ascertained clinically and confirmed by MINI.

      Study Enrollment Procedures Upon identifying a subject who meets the criteria for study
      participation, the physician providing care for that subject, or the coordinator acting on
      behalf of the physician with the physician's consent, will explain the study, answer any
      questions about the study and obtain informed consent.

      Study participants will be compensated a total of $400 for participation in this 1-week
      study, $0.00 at the time of completion of baseline assessments, and $400 at the time of
      completion of the end of study assessments.

      STUDY INTERVENTIONS The interventions in this study include a mobile health app, completion
      of pencil and paper DSST. Subjects will then complete the app-based version of the DSST.

      Description of Study Evaluations Consenting Procedure Eligible subjects will be recruited
      from the BCDF. All eligible subjects will engage in a thorough consenting process as it
      relates to the aims, objectives and hypotheses of the study. The voluntariness of all
      eligible subjects will be emphasized, and participation/ non-participation will have no
      impact on care recommendations. Upon completion of the consenting process, all eligible
      subjects will be asked to sign a consent form at the BCDF. Patients who are eligible will be
      explained the details of the study by the treating physician and will be provided with the
      opportunity to ask any questions before consent is obtained. A research study coordinator
      will explain the study and obtain and document consent using a Medical Ethics Board (MEB)
      approved consent form.

      Screening Screening of subjects for eligibility will be performed by research study staff and
      treating physicians either prior to the subject's visit or at the time of the visit. Subjects
      with MDD, as confirmed using M.I.N.I Version 5.0, who meet all the selection criteria are
      eligible for participation.

      Study Visits The study will consist of two visits, baseline and final visit. The paper DSST
      and the mobile app DSST will be completed at each of these visits. MADRS, HAM-A and SHAPS
      assessments will also be completed at baseline and final visit.

      Completion/Final Evaluation/Early Termination Subjects will complete a final visit. All
      eligible subjects will be informed that the ongoing provision of care will not be guaranteed.
      Necessary steps will be put in place to assure that subjects are made aware of mental health
      resources for ongoing care in emergency situations.
    

Intervention name(s): Pen and Paper Digit Symbol Substitution Test (DSST); Electronic Digit Symbol Substitution Test (DSST)- (a.k.a. Codebreaker)
Intervention type(s): Other; Other
Intervention description(s): The DSST is a paper-and-pencil cognitive test presented on a single sheet of paper that requires a subject to match symbols to numbers according to a key located on the top of the page. The subject copies the symbol into spaces below a row of numbers. The number of correct symbols within the allowed time, usually 90 to 120 seconds, constitutes the score.; Code breaker is the mobile/electronic version of the pen and paper DSST which is capable of identifying deficits in the domains of executive function, processing speed and attention/concentration, and takes 2 minutes to complete. Six symbols are numbered consecutively. Users are presented with a series of numbers that they must then match with the correct corresponding symbol as quickly as possible. Users are scored on speed and accuracy.
Intervention model: Single Group Assignment
Intervention model description: Thirty adults (18-65) with DSM-5 MDD will be enrolled at the BCDF Toronto, Ontario. All subjects will have their diagnosis confirmed by Mini International Neuropsychiatric Interview Version 6.0.
At baseline, data will be collected from all participants and will include demographics, comorbidities, medication history and concurrent medications. All subjects will be assessed symptomatically with the Montgomery and Asberg Depression Rating Scale (MADRS) as well as the Hamilton Anxiety Rating Scale (HAM-A), Snaith Hamilton Pleasure Scale (SHAPS) for anhedonia, as well as the paper and pencil version of the DSST at baseline and end of study (Day 7).
The DSST has been normed on the sex, age and gender. These norms will be used as reference. All subjects will complete the pencil and paper version of the DSST and complete the mobile app-based version of the DSST.
Masking: None (Open Label)
Primary purpose: Other