Effect of Action-Based Cognitive Remediation in Patients With Bipolar Disorder
Condition: Bipolar Disorder; Cognitive Impairment
MeSH terms: Cognitive Dysfunction; Bipolar Disorder
Study type: Interventional

Summary: 
      PRETEC-ABC aims to assess the effect of a new form of cognitive remediation, Action-Based
      Cognitive Remediation (ABCR), in patients with bipolar disorder in remission on cognition,
      and to assess the neural assays for treatment effects with the purpose of identifying a
      neural biomarker for pro-cognitive effect. It is hypothesized (i) that ABCR vs. a control
      treatment has a beneficial effect on cognition in remitted patients with bipolar disorder
      remission. It is hypothesized (ii) that this treatment-associated improvement of cognition
      translates into better functional capacity at a six months follow-up assessment (secondary
      outcome). Finally, as an exploratory measure, it is hypothesized that ABCR will produce an
      early change in frontal activity and that this activity will correlate with ABCR-associated
      improvements in cognitive function.
    

Detailed description: 
      The trial will include outpatients with BD in full or partial remission (a score ≤14 on the
      Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Recruitment will
      be carried out through the ongoing Bipolar Illness Onset (BIO) study, the Copenhagen
      Affective Disorder Clinic, Psychiatric Centre Copenhagen, Rigshospitalet, other mental health
      centres, consultant psychiatrists in the Capital Region of Denmark, and through
      advertisements on relevant websites.

      Participants will undergo an eligibility assessment followed by randomisation. When 4 - 6
      participants have been randomised to either the ABCR or the control group, the baseline
      assessments are carried out. The baseline assessment is completed over two days, 1 - 3 days
      apart. A fMRI scan is carried out on day 1 encompassing spatial and verbal working memory
      N-back tasks, a picture encoding task, a resting state and a structural scan. On day 2, a
      blood sample is drawn in the morning, followed by administration of a comprehensive
      neuropsychological test battery. Participants fill in questionnaires concerning subjective
      cognitive complaints, psychosocial functioning and quality of life and functional capacity is
      assessed using a clinician-rated interview and a performance based assessment. Sleep quantity
      and quality in the past three days is assessed. After two weeks of ABCR or control treatment,
      functional MRI, neuropsychological testing an assessment of mood and subjective cognition are
      repeated. These assessments, as well as assessments of functional capacity and quality of
      life, are repeated within two weeks after treatment completion and six months after treatment
      completion.

      Block randomisation is carried out by Pharma Consulting Group, stratified by gender and age
      (patients < or ≥ 35 years).

      Power calculation was also carried out by Pharma Consulting Group based on findings from a
      previous RCT in our group assessing the effect of 8 weeks of EPO treatment on the same
      cognitive composite score. In PreTEC-ABC, a clinically relevant difference between the ABCR
      and the control groups following 10 weeks of treatment is assumed to be 0.4 SD (corresponding
      to a medium effect size) on the primary outcome, with a mean change in the cognitive
      composite score of 0.5 SD. Assuming a 10% drop-out rate, we will recruit up to N=58 in order
      to achieve complete datasets for N=52 participants.

      Data will be analysed using mixed models using intention-to-treat (ITT) analyses.

      Functional MRI-data will be pre-processed and analysed with the FMRIB Expert Analysis Tool
      (FEAT) and the "randomize" algorithm implemented in FMRIB Software Library (FSL). Functional
      MRI data will be analysed using a Region of interest (ROI) analysis to assess differences
      between the ABCR and control group in neural activity in the dlPFC and the hippocampi after 2
      weeks. Exploratory whole-brain analyses will be conducted to investigate any effects in other
      brain regions. Any differences in neural activity will be correlated with potential changes
      in the cognitive composite score at weeks 2 and post-treatment. If there is a significant
      correlation with cognition at post-treatment, multiple regression analysis will be carried
      out, adjusting for mood and demographic characteristics, to assess whether early change in
      neural activity is predictive of pro-cognitive effects.
    

Intervention name(s): Action-Based Cognitive Remediation; Unstructured support group
Intervention type(s): Behavioral; Behavioral
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Biomarker; Bipolar Disorder; Cognition; Cognitive Impairment; cognitive remediation; functional magnetic resonance imaging; pro-cognitive effect