J025 Establishing feasibility for cell replacement therapy – outcomes from the trident (trial designs for delivery of novel therapies for neurodegeneration) trial

<h3>Background</h3> The use of progenitor cells to replace lost striatal neurons, known as cell replacement therapy (CRT), has the potential to restore the disruption in functional connectivity of the basal ganglia, which underpins Huntington’s disease (HD) symptoms. Previous studies have demonstrated proof-of-concept for CRT, but with variable results, possibly due to cautiously low numbers of cells being transplanted. <h3>Aims</h3> We wanted to evaluate CRT in HD, exploring innovative approaches for minimising the impact of design constraints and maximising efficiency for future trials. <h3>Methods</h3> A Trial within a Cohort (TWiC) design was employed to investigate the safety of fetal cell transplants in HD. Participants recruited to the wider observational cohort undertook clinical and functional assessments, with additional screening assessment to enter the surgical sub-cohort. Participants were then randomised from the surgical sub-cohort to receive CRT. A process evaluation was embedded throughout to assess suitability of trial processes. <h3>Results</h3> A total of 22 participants were recruited to the observational cohort and 7 participants underwent pre-operative assessment for CRT and 5 were eligible for surgery. No transplants were performed due to the impact of Covid-19 on availability of surgical theatres and fetal tissue. Findings from the process evaluation indicated that the design of TRIDENT was acceptable to both participants and the trial team, although small modifications could improve efficiency of data collection and participant experience. <h3>Conclusions</h3> The TWiC design is suitable for the evaluation of CRT in HD and provides a framework for evaluation of advanced therapies where blinding is not possible.