Background

The aim of this study is to examine the feasibility of a future definitive randomised controlled trial of Family Focused Treatment for Adolescents UK (FFT-A UK) in the management of early-onset bipolar disorder (EOBD) (under 18 years). The FFT-A has been evaluated in the USA to augment the pharmacological treatment of adolescents with bipolar disorder (BD). The FFT-A UK has been condensed to 16 sessions over approximately 6 months to be utilised within the UK National Health Service. Research from the USA suggests that families experience high levels of distress, stress, burden and family disharmony when living with a young person who has BD. The FFT-A UK is a family-based approach designed to increase understanding of BD (psycho-education), improve communication and increase ability to problem-solve.

Methods/design

The trial will examine the feasibility of a randomised, parallel group, non-blinded design and the procedures of a subsequent definitive trial. Thirty-three young people with BD and their families will be recruited. Participants will complete measures at baseline, on completion of the 6-month treatment and again after a further 6 months. The self-report measures include the Warwick Edinburgh Mental Well-being Scale, The McMaster Family Assessment Device (FAD), Conflict Behaviour Questionnaire aka 'Interaction Behaviour Questionnaire', EuroQuol EQ-5D-3L and EQ-5D-Y. Primary outcomes will be rates of eligibility, recruitment and retention, estimates of the variability in the self-report measures and assessment of the intervention delivery in the study population. Participants' qualitative views on the measures and intervention will be sought to confirm the acceptability of intervention and study design. The health economics component will establish how cost-effectiveness will be assessed in a future definitive trial.

Discussion

The study will produce a full trial protocol and amendments to the FFT-A UK to inform a well-designed multi-centre randomised controlled trial (RCT) as an adjunct to pharmacotherapy in the management of EOBD.

Trial registration

Current Controlled Trials ISRCTN59769322.

Visual function in vertebrates critically depends on the continuous regeneration of visual pigments in rod and cone photoreceptors. RPE65 is a well-established retinoid isomerase in the pigment epithelium that regenerates rhodopsin during the rod visual cycle; however, its contribution to the regeneration of cone pigments remains obscure. In this study, we use potent and selective RPE65 inhibitors in rod- and cone-dominant animal models to discern the role of this enzyme in cone-mediated vision. We confirm that retinylamine and emixustat-family compounds selectively inhibit RPE65 over DES1, the putative retinoid isomerase of the intraretinal visual cycle. In vivo and ex vivo electroretinography experiments in Gnat1-/- mice demonstrate that acute administration of RPE65 inhibitors after a bleach suppresses the late, slow phase of cone dark adaptation without affecting the initial rapid portion, which reflects intraretinal visual cycle function. Acute administration of these compounds does not affect the light sensitivity of cone photoreceptors in mice during extended exposure to background light, but does slow all phases of subsequent dark recovery. We also show that cone function is only partially suppressed in cone-dominant ground squirrels and wild-type mice by multiday administration of an RPE65 inhibitor despite profound blockade of RPE65 activity. Complementary experiments in these animal models using the DES1 inhibitor fenretinide show more modest effects on cone recovery. Collectively, these studies demonstrate a role for continuous RPE65 activity in mammalian cone pigment regeneration and provide further evidence for RPE65-independent regeneration mechanisms.