Video Games Among People With Schizophrenia
Condition: Cognitive Function; Schizophrenia and Disorders With Psychotic Features
MeSH terms: Schizophrenia; Mental Disorders; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders
Study type: Interventional

Summary: 
      The investigators aim to establish a research project to test the impact of gaming by
      carrying out a digital gaming interventions, monitoring its cognitive and clinical outcomes,
      while concurrently performing a multimodal brain imaging experiment.
    

Detailed description: 
      The effectiveness of the gaming intervention will be assessed using a controlled, controlled,
      single-blind clinical trial with a pragmatic, three-arm parallel-group design.

      Interventions: Participants will be randomised into three groups: Cognitive training
      (intervention group, CogniFit, N=78), entertainment video gaming (active control group,
      SIMS4, N=78) and treatment as usual (a passive control group, N=78). The mechanism of
      CogniFit (intervention) lies on the evidence for computerised exercises focusing on auditory
      and verbal processing, which are likely to yield improved verbal learning and memory and
      activate reward systems of the brain that drive brain plasticity in adults with
      schizophrenia. SIMS4 game (active control) offers entertainment without any known cognitive
      or health-related outcome. The data collection, subject recruitment and training will be
      carried out in an outpatient psychiatric units or outpatient clinics, mental health
      associations, and residential homes in Hong Kong. The study is aimed for patients' diagnoses
      of schizophrenia.

      Recruitment: An extended informed consent process will be used. The health service's medical
      records at the study site will be screened by the authority of the staff of the organisation.
      Patients will be screened to determine their eligibility for study participation. Eligible
      participant will first receive a short leaflet of the study from the staff or during a short
      information session organised for the participants to consider their availability. If an
      eligible patient shows interest, more detailed written and oral information will be shared.

      After signing informed consent forms (two identical copies), baseline data with background
      information, Intelligence Quotient (IQ, if available) and MMSE will be collected to show
      evidence of the participants' capacity to give informed consent. Medication dosage
      [chlorpromazine equivalence] will be collected as some medications currently used in
      schizophrenia may affect the response to cognitive training strategies.

      Recruitment will continue until the required sample size has been obtained.

      Randomisation: After baseline data collection, the Trial Manager will be informed (by email,
      text message, WhatsApp) about a new participant and he/she will allocate the participant to
      one of the three arms based on a list of computer-generated random numbers provided by an
      external clinical trial randomisation service (blocks of 6 consecutive patients, a 1:1:1
      ratio). Allocation will be masked to the outcome assessors, and the trial statistician, but
      it cannot be masked from the RAs who recruit the patients and the treatment staff working
      with the patients.

      For neuroimaging assessment (EEG, fMRI, resting state), a sub-sample from our total sample
      will be randomised at baseline. Randomisation will be based on a list of computer-generated
      random numbers.

      Power analysis and sample size: The investigators calculated the sample size based on (1) the
      number of actual pairwise tests to be made for the efficacy of the primary outcome and (2)
      the two-level modelling approach in the final data analysis, in which the type I error has
      been adjusted. The statistical efficiency will be ensured using the MANOVA method for
      multiple group comparison. First, given that video gaming is a fairly novel strategy, the
      investigators will base the sample size calculation (a priori) on a cognitive-efficacy
      meta-analysis for patients with schizophrenia showing and overall effect size (ES, Cohens' D)
      of 0.58 on verbal working memory (a primary outcome). Based on our hypothesis, the primary
      endpoints are the effects in verbal working memory at 3 and 6 months of cognitive training in
      the gaming group, in comparison with the other two groups: cognitive training vs.
      entertainment gaming, cognitive training vs. non-gaming control group. Four pairwise
      interactions between the contrast of the two comparisons and the two time points will be
      tested. For multiple comparison tests of four, for a type I error level of 5% (two-sided), an
      adjusted significant level should be = (1- (1- 0.05)4) /2 = 0.01274 /2 = 0.0064, and the
      corresponding z score for a one-sided test is 2.49. Given the effect size 0.58, assuming
      equal sample size of the three groups, with a statistical power of 0.8 and = 0.01274, the
      investigators require at least 198 subjects (66 per group) by applying the equation, 2(Z1- +
      Z1- /2)2 / ES2. According to a meta-analysis,40 the total sample size in previous cognitive
      training studies has typically been 50 (range 10-138).

      Using evidence-based rationale for patient flow in this study, the investigators can assume
      that about 60% of patients that will be screened will not be eligible for the study due to
      age or lack of capacity to participate in the study. Based on the literature, about 45% of
      patients with schizophrenia will refuse to participate in the RCT studies, and 16% will
      drop-out during the course of intervention. Thus, the investigators need a total of 234
      participants to be randomply allocated to three study groups, and 198 participants in
      follow-ups. Based on this knowledge, a total of 985 subjects need to be approached. The
      numbers are realistic given that the total number of patients with schizophrenia in our study
      sites is about 5,500, and the total number of schizophrenia patients in Hong Kong is 40,000.

      Second, for neuroimaging assessment, a sub-sample of 126 participants from our total sample
      (N = 198) will need (63%) to be randomised at baseline. Randomisation will be based on a list
      of computer-generated random numbers. The investigators assume that 30% will drop-out between
      baseline and the 3-month follow-up assessment, which leave us with 29 patients in each group
      (totally 87 participants at baseline). The sample size will be appropriate for our
      neuroimaging assessment; the average number of participants in RCT studies assessing patient
      cognition or changes in brain structure has been about 20.

      The investigators will also verify whether the interventions have been delivered as designed
      (intervention fidelity). Therefore, patient gaming logs (gaming frequency [number of gaming
      sessions per week], the length of each session [minutes], number of drop-outs) and patient
      gaming diaries including descriptions of possible strengths and limitations of the
      interventions will be analysed with the content analysis based on the data to be collected
      from patient diaries.
    

Intervention name(s): Cognifit; SIMS 4 (Maxis, Inc)
Intervention type(s): Behavioral; Behavioral
Intervention description(s): CogniFit is an Internet browser-based digital brain training program, to improve cognitive abilities based on a personalised brain training regimen. Participants are instructed to play all games assigned by cognifit from three categories (memory, spatial perception, and mental planning) during each training session. After playing the games in these three categories, they are free to choose which exercises they wish to play.; The Sims 4 is a life simulation PC game. It is purely an entertainment game without known cognitive or health-related outcomes. Does not iclude high-intensity action and competition. This specific game and non-competitive games like it in general do not improve attention, working memory, or other cognitive abilities despite being engaging and fun.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A controlled, single-blind clinical trial with a pragmatic, three-arm parallel-group design.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Cognitive Function; Schizophrenia and Disorders with Psychotic Features; Computers, Digital