Modulating delirium through stimulation (MoDeSt): study protocol for a randomized, double-blind, sham-controlled trial assessing the effect of postoperative transcranial electrical stimulation on delirium incidence

Background: Postoperative delirium (POD) is the most common neurological adverse event among elderly patients undergoing surgery. POD is associated with an increased risk for postoperative complications, long-term cognitive decline, an increase in morbidity and mortality as well as extended hospital stays. Delirium prevention and treatment options are currently limited. This study will evaluate the effect of transcranial electrical stimulation (tES) on the incidence of POD. Methods: We will perform a randomized, double-blind, sham-controlled trial using single-session postoperative application of tES (alpha-tACS over posterior parietal cortex (PPC), anodal tDCS over left dorsolateral prefrontal cortex (DLPFC), 2 mA, 20 min; sham, 2 mA, 30 s) in the recovery room in 225 patients (>65 years) undergoing elective major surgery. Patients will be randomly allocated to one of three study groups (tACS, tDCS, sham) with a 1:1:1 ratio. Delirium will be screened twice daily with the 3-minute diagnostic interview Confusion Assessment Method (3D-CAM) in the five days following surgery. The primary outcome is the incidence of POD that will be tested between tACS and sham. Secondary outcomes include delirium severity, duration, postoperative pain, electroencephalographic (EEG) markers, and fluid biomarkers. Discussion: If effective, tES is a novel, easily applicable, non-invasive method to prevent the occurrence of POD. The comprehensive neurophysiological and biofluid assessments for markers of (neuro-)inflammation and neurodegeneration will shed light on the pathomechanisms behind POD and further elucidate the (after-)effects of tES. The potential implications for the postoperative recovery comprise enhanced patient safety, neurocognitive outcome, perioperative manageability but also reduced healthcare costs. Trial registration: German Clinical Trial Registry, DRKS00033703, registered on 23 February 2024. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial DRKS00033703 ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of University Medicine Greifswald gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.