Delirium Treatment With Transcranial Electrical Stimulation

NCT ID: NCT06285721

Last Updated: 2024-07-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-24
• Study Completion Date: 2027-03-31

Brief Summary

The goal of this clinical trial is to investigate the effectiveness of standardized and personalized transcranial alternating current stimulation (tACS) in patients with delirium. To investigate this, will perform a double-blind, randomized, sham-controlled, multicenter trial.

To test the safety and feasibility of tACS in delirious patients, the first 30 patients will be randomized to receive either active or sham tACS treatment in a 1:1 ratio through a pilot study. For the main phase of the study, patients will be randomized, resulting in an overall 1:1:1 allocation to standardized tACS, personalized tACS or sham treatment.

Electroencephalogram (EEG) will be measured directly before and directly after the first stimulation session to assess whether tACS can reduce relative delta power. tACS or sham treatment will be given once daily for a maximum of 14 days, or until resolution of delirium or discharge (whichever comes first). During the treatment phase, presence and severity of delirium will be assessed daily. After the treatment phase, an additional EEG will be measured. Cognitive status will be assessed three months after the initial tACS session.

Detailed Description

Delirium, a prevalent neuropsychiatric syndrome caused by an underlying medical condition, characterized by cognitive deficits such as inattention, extends hospital stay, increases healthcare costs and increases the risk of long-term cognitive decline. Prolonged and severe delirium is associated with worse long-term outcomes. There is currently no treatment that reduces the duration or severity of delirium.

Delirium is consistently characterized by diffuse oscillatory slowing of the EEG, including pronounced loss of alpha activity and increased relative delta power. Additionally, functional connectivity between brain regions is decreased during delirium. In light of this, tACS is a potential treatment option that directly addresses the brain dysfunction observed in delirium. Because tACS has shown the ability to improve multiple domains of cognition, including attention, and modify functional connectivity, we aim to investigate the effectiveness of tACS as treatment for delirium. We will utilize the EEG to measure the effects of tACS, using relative delta power as a primary outcome measure.

Additionally, EEG measurements can capture individual spectral and connectivity changes targeted with tACS, making EEG a promising input for personalized tACS treatment. Neural mass modelling is a way to model the behavior of groups of neurons resulting in oscillatory output similar to EEG. This type of model is able to represent delirium pathology and, when combined with individual EEG input, can be employed to optimize treatment effectiveness, leading to personalized tACS treatment.

The overarching aim of the study is to investigate whether treatment with tACS, either standardized or personalized, induces EEG alterations indicative of reversal of delirium. The primary outcome is relative delta power in the EEG measured after the first tACS session. Secondary outcomes include severity and/or duration of delirium measured with validated delirium assessment instruments.

Patients aged 50 years and older with delirium that persists for at least 2 days, despite adequate treatment of underlying causes will be included in the study (n = 159). Inclusion will take place in the intensive care unit (ICU) and non-ICU wards of the University Medical Centre (UMC) Utrecht, Radboud UMC and HagaZiekenhuis.The proposed tACS protocol is considered safe according to the latest published international safety guidelines. All participants will be screened for their relevant medical history and other tACS safety aspects.

Conditions

Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Standardized treatment arm

Standardized tACS will be applied with 2.0 mA (peak-to-peak) intensity for 30 minutes, with a 10 Hz frequency. Two 5x5 cm saline-soaked electrodes located at the frontal and occipito-parietal part of the scalp will be utilized (corresponding to 10-20 EEG electrode locations POz-Oz and AFz), including in the stimulation field the DLPFC, precuneus and posterior cingulate cortex. At the beginning of stimulation, the intensity will ramp up for 30 seconds to 2.0 mA peak-to-peak, while at the end of stimulation, the intensity will ramp down for 30 seconds.

Group Type: EXPERIMENTAL

transcranial alternating current stimulation (tACS)

Intervention Type: DEVICE

tACS is a non-invasive brain stimulation technique which involves the application of a low intensity electric current between two or more surface electrodes. tACS uses stimulation with a current alternating at a specific frequency that can entrain endogenous neuronal oscillations by inducing neural synchronization. The administration of tACS is proposed to phase-lock large populations of neurons in the superficial layers of the cerebral cortex causing neural synchronization in the corresponding frequency, thereby altering connectivity. tACS will be delivered via a transcranial electrical stimulation (tES) device (Nurostym tES, Brainbox Ltd, United Kingdom). This device has been CE-marked for use as a medical device for the treatment of mental and neurological disorders.

Personalized treatment arm

Personalized tACS will be applied with 2.0 mA (peak-to-peak) intensity for 30 minutes with a 30 second ramp up and ramp down. Treatment will be personalized based on a delirium neural mass model. After fitting the model to the individual EEG, a virtual tACS trial allows for optimization of treatment parameters for each individual patient. Treatment optimization will take place through changing stimulation location and/or frequency. After determining the optimal individual treatment strategy, settings of the personalized stimulation will remain constant during the treatment phase.

Group Type: EXPERIMENTAL

transcranial alternating current stimulation (tACS)

Intervention Type: DEVICE

tACS is a non-invasive brain stimulation technique which involves the application of a low intensity electric current between two or more surface electrodes. tACS uses stimulation with a current alternating at a specific frequency that can entrain endogenous neuronal oscillations by inducing neural synchronization. The administration of tACS is proposed to phase-lock large populations of neurons in the superficial layers of the cerebral cortex causing neural synchronization in the corresponding frequency, thereby altering connectivity. tACS will be delivered via a transcranial electrical stimulation (tES) device (Nurostym tES, Brainbox Ltd, United Kingdom). This device has been CE-marked for use as a medical device for the treatment of mental and neurological disorders.

Sham treatment arm

At the beginning and end of this 30-minute protocol, the tACS device will ramp up to 2.0 mA peak-to-peak intensity for 30 seconds, stimulate for 60 seconds and ramp down for 30 seconds, which mimics the sensation of actual tACS stimulation and improves blinding.

Group Type: SHAM_COMPARATOR

Sham transcranial alternating current stimulation (tACS)

Intervention Type: DEVICE

Sham-tACS is a form of non-effective stimulation which can mimic the subjective sensation of active tACS treatment. During sham-tACS, the device will ramp up to 2.0 mA peak-to-peak intensity for 30 seconds, stimulate for 60 seconds and ramp down for 30 seconds, which mimics the sensation of actual tACS stimulation and improves blinding.The sham-tACS will be delivered via a transcranial electrical stimulation (tES) device (Nurostym tES, Brainbox Ltd, United Kingdom). This device has been CE-marked for use as a medical device for the treatment of mental and neurological disorders.

Interventions

transcranial alternating current stimulation (tACS)

tACS is a non-invasive brain stimulation technique which involves the application of a low intensity electric current between two or more surface electrodes. tACS uses stimulation with a current alternating at a specific frequency that can entrain endogenous neuronal oscillations by inducing neural synchronization. The administration of tACS is proposed to phase-lock large populations of neurons in the superficial layers of the cerebral cortex causing neural synchronization in the corresponding frequency, thereby altering connectivity. tACS will be delivered via a transcranial electrical stimulation (tES) device (Nurostym tES, Brainbox Ltd, United Kingdom). This device has been CE-marked for use as a medical device for the treatment of mental and neurological disorders.

Intervention Type: DEVICE

Sham transcranial alternating current stimulation (tACS)

Sham-tACS is a form of non-effective stimulation which can mimic the subjective sensation of active tACS treatment. During sham-tACS, the device will ramp up to 2.0 mA peak-to-peak intensity for 30 seconds, stimulate for 60 seconds and ramp down for 30 seconds, which mimics the sensation of actual tACS stimulation and improves blinding.The sham-tACS will be delivered via a transcranial electrical stimulation (tES) device (Nurostym tES, Brainbox Ltd, United Kingdom). This device has been CE-marked for use as a medical device for the treatment of mental and neurological disorders.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age over 50 years.
• Diagnosis of delirium
• Richmond Agitation and Sedation Scale (RASS) score of -2 to +2.
• Delirium duration of at least two days prior to study inclusion, based delirium assessments and/or descriptions in the medical and/or nursing files.
• Known causes underlying delirium are being treated adequately, as assessed by the treating physician.

Exclusion Criteria

• Inability to conduct delirium assessment (e.g. coma, deaf, blind) or inability to speak Dutch or English.
• A moribund state.
• Alcohol/substance abuse withdrawal or stroke as precipitating factor for delirium.
• Diagnosis of dementia, based on medical record review and/or a score of ≥4.5 on the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)
• One or more contra-indications for tACS:

1. History of serious head trauma or brain surgery;

2. Large or ferromagnetic metal parts in the head (except for a dental wire);

3. Implanted cardiac pacemaker or neurostimulator;

4. Skin diseases or inflammations;

5. Epilepsy.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

HagaZiekenhuis

OTHER

Sponsor Role: collaborator

A.J.C. Slooter

OTHER

Sponsor Role: lead

Responsible Party

A.J.C. Slooter

Professor of Intensive Care Neuropsychiatry

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Arjen JC Slooter, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

Radboudumc

Nijmegen, Gelderland, Netherlands

Site Status: RECRUITING

HagaZiekenhuis

The Hague, South Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Yorben Lodema, MD

Role: CONTACT

deltes@umcutrecht.nl

088 7558300

Julia van der A, MSc

Role: CONTACT

j.vandera-2@umcutrecht.nl

088 756 7523

Facility Contacts

Indira Tendolkar, MD, PhD

Role: primary

Thomas H Ottens, MD, PhD

Role: primary

References

van der A J, Lodema Y, Ottens TH, Schutter DJLG, Emmelot-Vonk MH, de Haan W, van Dellen E, Tendolkar I, Slooter AJC. DELirium treatment with Transcranial Electrical Stimulation (DELTES): study protocol for a multicentre, randomised, double-blind, sham-controlled trial. BMJ Open. 2024 Nov 2;14(11):e092165. doi: 10.1136/bmjopen-2024-092165.

Reference Type: DERIVED

PMID: 39488424 (View on PubMed)

Other Identifiers

DELTES

Identifier Type: -

Identifier Source: org_study_id