DELirium treatment with Transcranial Electrical Stimulation (DELTES): study protocol for a multicentre, randomised, double-blind, sham-controlled trial

Abstract

Introduction: Delirium, a clinical manifestation of acute encephalopathy, is associated with extended hospitalisation, long-term cognitive dysfunction, increased mortality and high healthcare costs. Despite intensive research, there is still no targeted treatment. Delirium is characterised by electroencephalography (EEG) slowing, increased relative delta power and decreased functional connectivity. Recent studies suggest that transcranial alternating current stimulation (tACS) can entrain EEG activity, strengthen connectivity and improve cognitive functioning. Hence, tACS offers a potential treatment for augmenting EEG activity and reducing the duration of delirium. This study aims to evaluate the feasibility and assess the efficacy of tACS in reducing relative delta power.

Methods and analysis: A randomised, double-blind, sham-controlled trial will be conducted across three medical centres in the Netherlands. The study comprises two phases: a pilot phase (n=30) and a main study phase (n=129). Participants are patients aged 50 years and older who are diagnosed with delirium using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria (DSM-5-TR), that persists despite treatment of underlying causes. During the pilot phase, participants will be randomised (1:1) to receive either standardised (10 Hz) tACS or sham tACS. In the main study phase, participants will be randomised to standardised tACS, sham tACS or personalised tACS, in which tACS settings are tailored to the participant. All participants will undergo daily 30 min of (sham) stimulation for up to 14 days or until delirium resolution or hospital discharge. Sixty-four-channel resting-state EEG will be recorded pre- and post the first tACS session, and following the final tACS session. Daily delirium assessments will be acquired using the Intensive Care Delirium Screening Checklist and Delirium Observation Screening Scale. The pilot phase will assess the percentage of completed tACS sessions and increased care requirements post-tACS. The primary outcome variable is change in relative delta EEG power. Secondary outcomes include (1) delirium duration and severity, (2) quantitative EEG measurements, (3) length of hospital stay, (4) cognitive functioning at 3 months post-tACS and (5) tACS treatment burden. Study recruitment started in April 2024 and is ongoing.

Ethics and dissemination: The study has been approved by the Medical Ethics Committee of the Utrecht University Medical Center and the Institutional Review Boards of all participating centres. Trial results will be disseminated via peer-reviewed publications and conference presentations.

Trial registration number: NCT06285721.

Keywords: Delirium; Electroencephalography; Randomized Controlled Trial.

Figure 1. Study flow chart. EEG, electroencephalography; tACS, transcranial alternating current stimulation; T, treatment; V, visit.

Figure 2. Standardised approach for applying transcranial alternating current stimulation (tACS). (A) Representation of the electrode placement. Two 5×5 cm electrodes will be positioned over AFz (anterior) and Oz (posterior) locations, indicated by coloured squares (blue for posterior, yellow for anterior). (B) Visualisation of the electric field distribution in the brain during tACS with an intensity of 2 mA (peak to peak). The colour map represents the magnitude of the electric field (magnE), measured in volts per metre (V/m). SimNIBS software (version 4) was used for simulation.