Title: Cognitive Remediation in Bipolar (CRiB2): a randomised trial assessing efficacy and_x000D_ mechanisms of cognitive remediation therapy compared to treatment as usual
Funder: Medical Research Council

Abstract: Background: Bipolar disorder (BD) is a common, serious condition. Episodes affect mood and energy, fluctuating between very low (depression), high (mania) or a mixture of these (mixed). Effects on work, relationships and quality of life can be devastating, adversely impacting people with BD, those close to them, health and economic systems. The World Health Organisation state that BD is second only to brain injury in the impact it has on ability to work. Disability for many people with BD is caused by “cognitive impairment” -difficulties with thinking skills such as recalling information, attention and planning. Cognitive impairments are a major concern for people with BD even when not in episodes. Treatment currently focuses on short-term mood but these ongoing, disabling difficulties are often overlooked in healthcare, despite directly affecting abilities to function well in daily life. They also affect long-term recovery prospects. _x000D_ A potential therapy for functioning: For people with schizophrenia (who have similar cognitive impairments), a psychological therapy – cognitive remediation (CRT) – provides meaningful, long-lasting benefits, such that it is now recommended internationally. Recent small trials suggest that CRT could improve the lives of people with BD. In our study with 60 participants, CRT improved cognition and function with benefits remaining 3 months after therapy. The existing studies are promising, but not big enough to confidently show whether CRT is an effective treatment for BD, so we are proposing a larger study aiming to show whether CRT is effective at improving everyday and cognitive functioning and indicate what factors are causing any benefits found._x000D_ This project: We will recruit 250 people from a range of sources (e.g. health services and places in the community) and randomly allocate them to receive 12 weeks of either evidence-based CRT (125 people) or continue usual care without CRT (125 people). We will test their cognitive skills and everyday functioning before and after the 12week programme, then 3 months later. We will compare these two groups to see whether CRT is better than usual treatment at improving everyday (including work-related) and cognitive functioning. To explore what makes the therapy effective, we will also test whether CRT affects peoples’ knowledge about their cognitive skills, stress hormones and mood instability and whether these changes relate to improved functioning. This may help increase future benefits that CRT could provide._x000D_ Public involvement & dissemination: We are working with the charity Bipolar UK and people with BD to help ensure we research CRT in ways most relevant to those affected. Our study proposal has been reviewed by people affected by BD and focus groups are influencing the final details. Their feedback has also informed which measure (psychosocial functioning) we chose as the main outcome of the trial and improved the language of public facing writing. Going forward, named service users will contribute to study documents as well be in trial steering groups. Our work so far with people affected by BD confirms a keenness for psychological therapies and wish to improve their functioning at work, socially and cognitively (all core parts of our ‘everyday functioning’ outcome measure). Service users will be involved in dissemination via charities and support groups; results will be shared with participants, public media channels, scientific meetings and journals (with articles accessible to anyone).

Lay abstract: Research question: We will establish whether cognitive remediation therapy (CRT) provides meaningful benefits compared to treatment as usual (TAU) for people with bipolar disorders (BD)._x000D_ Background: People with BD experience difficulties with cognitive functioning, even outwith mood episodes, and these difficulties contribute markedly to problems in everyday functioning and quality of life. Although these impairments are important targets for intervention, evidence-based treatment is not available for clinical practice. CRT targets fundamental cognitive functions such as memory, attention, and executive functioning, and has been proven to improve these in people diagnosed with other psychoses. Preliminary evidence indicates significant potential for CRT to help people with BD. Our pilot randomised controlled trial (RCT; “CRiB1”) examined 60 people with BD randomised to receive an established 12-week CRT programme in addition to TAU, or TAU alone. The trial and intervention were both found to be feasible and acceptable; CRT was rated as desirable and led to improved cognitive and psychosocial functioning compared to TAU alone. However, CRiB1 was not powered to infer intervention efficacy._x000D_ Aims: Our proposed Cognitive Remediation in Bipolar efficacy RCT (CRiB2) will determine whether CRT is efficacious in an adequately powered sample (N=250) of people with BD. The primary efficacy outcome is psychosocial functioning three months after the intervention endpoint (CRT+TAU versus TAU groups), i.e., six months after randomisation. CRiB2 also investigates CRT’s mechanism of action by examining factors that may mediate the relationship between CRT and the primary outcome._x000D_ Methods: CRiB2 is a multisite, single-blind RCT comparing CRT+TAU (n=125) with TAU (n=125) for participants with BD, aged 18-65, not currently in an illness episode. The therapist-led computerised CRT programme (CIRCuiTS) is evidence-based on trials in psychotic illnesses. Data will be collected and analysed by investigators blinded to group allocation. After a baseline visit and randomisation (week 0), the participant will receive either CRT+TAU or TAU alone (weeks 1-12) and outcomes assessed at week 13 and 25 (primary outcome endpoint). We will also collect secondary outcomes including cognitive function (processing speed, attention, memory, verbal fluency, executive functioning, and a global cognitive composite measure), achievement of self-defined goals, self-rated cognitive difficulties, and quality of life. Primary and secondary outcomes will be compared between CRT+TAU with TAU groups via intention-to-treat analyses. We will assess whether CRT drives changes in global cognition, levels of cortisol, fluctuations in mood and metacognitive skills, and if these changes are associated with primary outcome changes in functioning (mediation effects)._x000D_ Timelines: The project duration is 3years + 5months; 250 participants will be randomised (by year2, month6), followed up (by year3) before data analysis and dissemination (project end)._x000D_ Potential impacts: Results will be reported in scientific and public domains. If efficacious, CRiB2 will represent a breakthrough by providing evidence of efficacy for a psychological intervention benefiting cognitive and psychosocial functioning in BD. This cognitive-enhancing therapy for BD would have the potential to markedly reduce burden for the many sufferers who experience deficits in functioning.

Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH