Accelerating assessment of disease modification in Parkinsons via multi-arm, multi-stage design: the EJS ACT-PD initiative

<h3>Background</h3> Identifying a disease-modifying therapy (DMT) for Parkinson’s disease (PD) is a major unmet need. Inefficiencies in the current clinical trials process have resulted in lengthy evaluation timeframes; unclear assessment of clinically meaningful change; and limited generalisability of findings due to un-representative trial populations. <h3>Aim</h3> To produce an inclusive multi-arm, multi-stage (MAMS) trial platform to increase scale and pace of PD research. <h3>Methods</h3> &gt;90 key UK stakeholders, including people with PD (PwP) and care partners have addressed specific issues regarding: trial design, outcome measures, therapy selection, infrastructure, funding, and patient inclusion. Decisions have been further informed by community input; an international advisory group; the MHRA; and a UK-wide Site Capability Survey. <h3>Results</h3> Telmisartan, terazosin and UDCA will be assessed over 3 years of treatment. PwP on dopamine replacement therapy without dementia will be eligible. The primary outcome measures is the UPDRS parts 1 and 2 combined. 97 potential sites have been categorised into expertise-related tiers. <h3>Conclusions</h3> We have co-designed a MAMS trial protocol to assess potential DMTs for PD. Aiming to recruit from December 2024 across 40 UK sites, the trial will provide ongoing research opportunities, strengthen UK PD research infrastructure, and promote research inclusivity.