One potential very impactful application of Human Digital Twin technology is that of In-Silico Trials. In this lecture the development and status of an IST for Acute Ischemic Stroke will be introduced. This In-Silico Stroke Trial is the result of a pan-European collaboration (in the EU funded project INSIST, https://www.insist-h2020.eu), and is a hybrid of statistical models (e.g. the virtual population model) and mechanistic models (e.g. for thrombectomy or brain tissue perfusion). All models are integrated relying on a discrete event simulation. First results in relation to a retrospective reproduction of the seminal Mr Clean clinical trial will be discussed.