Effect of action-based cognitive remediation on cognition and neural activity in bipolar disorder:Study protocol for a randomized controlled trial

Abstract Background Cognitive impairment is present in bipolar disorder (BD) during the acute and remitted phases and hampers functional recovery. However, there is currently no clinically available treatment with direct and lasting effects on cognitive impairment in BD. We will examine the effect of a novel form of cognitive remediation, action-based cognitive remediation (ABCR), on cognitive impairment in patients with BD, and explore the neural substrates of potential treatment efficacy on cognition. Methods/design The trial has a randomized, controlled, parallel-group design. In total, 58 patients with BD in full or partial remission aged 18–55 years with objective cognitive impairment will be recruited. Participants are randomized to 10 weeks of ABCR or a control group. Assessments encompassing neuropsychological testing and mood ratings, and questionnaires on subjective cognitive complaints, psychosocial functioning, and quality of life are carried out at baseline, after 2 weeks of treatment, after the end of treatment, and at a six-month-follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and 2 weeks into treatment. The primary outcome is a cognitive composite score spanning verbal memory, attention, and executive function. Two complete data sets for 52 patients will provide a power of 80% to detect a clinically relevant between-group difference on the primary outcome. Behavioral data will be analyzed using mixed models in SPSS while MRI data will be analyzed with the FMRIB Expert Analysis Tool (FEAT). Early treatment-related changes in neural activity from baseline to week 2 will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest and with an exploratory whole-brain analysis. Discussion The results will provide insight into whether ABCR has beneficial effects on cognition and functioning in remitted patients with BD. The results will also provide insight into early changes in neural activity associated with improvement of cognition, which can aid future treatment development. Trial registration Clinicaltrials.gov, NCT03295305. Registered on 26 September 2017

Daily electronic self-monitoring of subjective and objective symptoms in bipolar disorder - The MONARCA trial protocol (MONitoring, treAtment and pRediCtion of bipolAr disorder episodes): a randomised controlled single-blind trial

INTRODUCTION: Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms. It has never been tested in a randomised clinical trial whether electronic self-monitoring improves outcomes in bipolar disorder. We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder. METHODS: We developed the MONARCA application for Android-based Smartphones, allowing patients suffering from bipolar disorder to do daily self-monitoring—including an interactive feedback loop between patients and clinicians through a web-based interface. The effect of the application was tested in a parallel-group, single-blind randomised controlled trial so far including 78 patients suffering from bipolar disorder in the age group 18–60 years who were given the use of a Smartphone with the MONARCA application (intervention group) or to the use of a cell phone without the application (placebo group) during a 6-month study period. The study was carried out from September 2011. The outcomes were changes in affective symptoms (primary), social functioning, perceived stress, self-rated depressive and manic symptoms, quality of life, adherence to medication, stress and cognitive functioning (secondary and tertiary). ANALYSIS: Recruitment is ongoing. ETHICS: Ethical permission has been obtained. DISSEMINATION: Positive, neutral and negative findings of the study will be published. REGISTRATION DETAILS: The trial is approved by the Regional Ethics Committee in The Capital Region of Denmark (H-2-2011-056) and The Danish Data Protection Agency (2013-41-1710). The trial is registered at ClinicalTrials.gov as NCT01446406