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

Caroline V Ott, Maj Vinberg, Christopher R Bowie, Ellen Margrethe Christensen, Gitte M Knudsen, Lars V Kessing, Kamilla W Miskowiak, Caroline V Ott, Maj Vinberg, Christopher R Bowie, Ellen Margrethe Christensen, Gitte M Knudsen, Lars V Kessing, Kamilla W Miskowiak

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.

Keywords: Biomarker; Bipolar disorder; Cognition; Cognitive impairment; Cognitive remediation; Functional magnetic resonance imaging; Pro-cognitive effect.

Conflict of interest statement

Ethics approval and consent to participate

The study has been approved by the Ethics Committee in the Capital Region of Denmark (protocol H-16043480) and the Danish Data Protection Agency (2012-58-0004). It was retrospectively registered at https://ichgcp.net/clinical-trials-registry/NCT03295305?term=NCT03295305&rank=1). Written informed consent will be obtained from all participants. Any important changes in the protocol will be reported to the Ethics Committee in the Capital Region of Denmark and the Danish Data Protection Agency.

Consent for publication

Not applicable.

Competing interests

KWM has received consultant fees from H. Lundbeck and Allergan. MV has received consultancy fees from H. Lundbeck and Astra Zeneca within the last 3 years. LVK has been a consultant for H. Lundbeck, AstraZeneca, and Sunovion within the last 3 years. EMC has received honoraria from H. Lundbeck within the last 3 years. CRB has received honoraria from Boehringer Ingelheim, Lundbeck, Otsuka, and Abbie. CVO has no competing interests. GMK has not received any honoraria from pharmaceutical companies within the last 3 years. The computer software used in the ABCR group is provided free of charge by HappyNeuron Pro (www.happyneuronpro.com).

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow diagram
Fig. 2
Fig. 2
Schedule of enrolment, interventions, and assessments. OTS One Touch Stockings of Cambridge, FAST Functional Assessment Short Test, SWM spatial working memory, RVP Rapid Visual Information Processing, RAVLT Rey Auditory Verbal Learning Test, RBANS Repeatable Battery for the Assessment of Neuropsychological Status, WAIS-III LNS Wechsler Adult Intelligence Scale Version III Letter–Number Sequencing, TMT-A Trail Making Test A, TMT-B Trail Making Test B, UPSA-B Brief Performance-Based Skills Assessment of the University of California, San Diego, SDS Sheehan Disability Scale, AQoL Assessment of Quality of Life, WHOQOL-BREF World Health Organization's Quality of Life Assessment, COBRA Cognitive Complaints in Bipolar Disorder Rating Assessment, WSAS Work and Social Adjustment Scale, WHODAS World Health Organization Disability Assessment Schedule, DART Danish Adult Reading Test, CTQ Child Trauma Questionnaire, SCIP-D Screen for Cognitive Impairment in Psychiatry—Danish version

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