Study protocol of the PRINCESS trial - PReoperative INtermittent fasting versus CarbohydratE loading to reduce inSulin resiStance versus standard of care in orthopaedic patients: a randomised controlled trial

Introduction Surgical trauma induces a metabolic stress response, resulting in reduced insulin sensitivity and hyperglycaemia. Postoperative insulin resistance (IR) is associated with postoperative complications, and extended preoperative fasting may further aggravate the postoperative metabolic stress response. Nutritional strategies, such as carbohydrate loading (CHL), have been successfully used to attenuate postoperative IR. Recent evidence suggests that time-restricted feeding (TRF), a form of intermittent fasting, improves IR in the general population, even after a short period of TRF. We hypothesise that TRF, as well as CHL, improve postoperative IR. Methods and analysis This open-label, single-centre, randomised controlled trial will compare the effect of short-term preoperative TRF, CHL and standard preoperative fasting on perioperative IR. A total of 75 orthopaedic patients presenting for elective intermediate to major surgery at a Dutch academic hospital will be randomly assigned to a control group (standard preoperative fasting), a TRF group or a CHL group. The primary outcome is postoperative IR, based on the updated homeostasis model assessment of IR, on the first day after surgery. Statistical analyses are performed using Student's t-tests or Mann-Whitney U tests. Ethics and dissemination The local medical ethics committee of the Amsterdam UMC, the Netherlands, approved the trial protocol in January 2023 (NL81556.018.22). No publication restrictions apply, and the results of the study will be disseminated through a peer-reviewed journal. Trial registration number NCT05760339.