Background: A systematic discovery pipeline approach to stroke recovery intervention development is rare. The limited number of early-phase dose trials has resulted in a lack of consideration for the complexity of dose and its role within an intervention.
Aim: To determine the tolerable dose range of an upper limb motor intervention conducted late (3-24 months) post-stroke. It is hypothesised that the maximum tolerated dose regimen will be higher than the dose of usual care currently provided.
Methods: Multidimensional Phase I dose-ranging trial that tests dose levels using a 3+3 rule-based design. The dose is subsequently adapted through escalation or de-escalation in response to data and according to pre-determined criteria. The trial will escalate two dimensions of dose: number of sessions per day (range 2-4 sessions/day) and total time in therapy across the day (range 3-6 hours/day). All dose dimensions (e.g., time-on-task) will be recorded. The trial delivers usual care upper limb motor therapy per the Australian Living Clinical Stroke Guidelines. The starting dose is 6 hours of therapy delivered over 4 x 90-minute sessions per day. People 3 to 24 months post-stroke with a Rating of Everyday Arm-use in Community and Home (REACH) score of 1 to 3 are eligible. Trial Registration: ACTRN12620000215921.
Results: Recruitment to commence in mid-2025.
Conclusion: This innovative trial design will determine the minimum to maximum dose range of an upper limb motor intervention late post-stroke. This outcome will inform the selection of doses to test in a Phase IIA trial to determine signal of efficacy.