Delirium Treatment With Transcranial Electrical Stimulation

Delirium Clinical Trial

— DELTES  

Official title:

DELirium Treatment With Transcranial Electrical Stimulation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06285721
• Other study ID #: DELTES
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 26, 2024
• Est. completion date: March 31, 2027

Study information

• Verified date: February 2024
• Source: UMC Utrecht
• Contact: Yorben Lodema, MD
• Phone: 088 7558300
• Email: deltes[@]umcutrecht.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to investigate the effectiveness of standardized and personalized transcranial alternating current stimulation (tACS) in patients with postoperative 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 postoperative.

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.

Surgical patients aged 50 years and older with postoperative 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 159
• Est. completion date: March 31, 2027
• Est. primary completion date: January 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Age over 50 years.

• Diagnosis of postoperative delirium that started within the first three days after surgery.

• 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 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.

Related Conditions & MeSH terms

• Delirium

Intervention

Device:
• 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.
• 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.

Locations

Country	Name	City	State
Netherlands	HagaZiekenhuis	Den Haag	Zuid-Holland
Netherlands	Radboudumc	Nijmegen	Gelderland

Sponsors (3)

Lead Sponsor	Collaborator
A.J.C. Slooter	HagaZiekenhuis, Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative delta power	Calculated by dividing the absolute power in the delta frequency range by the total power, assessed using 64-channel resting-state EEG directly before and after tACS.	1 day
Secondary	Duration of delirium	Delirium duration is evaluated by counting the number of days delirium is observed during the treatment period. We utilize the Intensive Care Delirium Screening Checklist (ICDSC), comprising 8 items, with a score of 4 or higher indicating the presence of delirium. Additionally, the Richmond Agitation-Sedation Scale (RASS), a 10-point scale ranging from +4 to -5, is used to assess the level of sedation (-5 indicating total sedation, +4 indicating combative behavior). A RASS score of -4 or lower, followed by an ICDSC score of 4 or higher, is also considered a delirium day.	Two weeks
Secondary	Severity of delirium	The cumulative score on the Intensive Care Delirium Screening Checklist (ICDSC), which includes 8 items and has a score range of 0-8, is documented for each day where delirium is observed during the hospital admission. In instances where the ICDSC score is unavailable, it will be approximated using information retrieved from the electronic patient record and standard delirium assessment tools routinely conducted.	Two weeks
Secondary	Length of hospital stay	The total number of days admitted to hospital	3 months
Secondary	Cognitive status three months post delirium	Score on the Telephone Interview for Cognitive Status Modified (TICS-M). The TICS-M is a brief, 13-item test of cognitive functioning with scores ranging from 0 to 50, with higher scores indicating better cognitive performance.	3 months
Secondary	Subjective sensations during treatment	Score on three-point Likert-type scale to assess sensations experienced during transcranial alternating current stimulation (tACS). The scale ranged from 0, indicating 'no sensation,' to 1, indicating 'slight sensation,' and 2, indicating 'intense sensation.' These sensations included itch, pain, burning sensation, heat, iron taste, headache, neck pain, phosphenes, dizziness, and nausea.	Two weeks
Secondary	Average peak frequency	Average peak frequency values will be calculated by averaging, over epochs, the peak frequency, assessed using 64-channel resting-state EEG before and after tACS and during the follow-up measurement.	Two weeks
Secondary	Phase Lag Index	Phase lag index captures phase synchronization between different EEG channels, assessed using 64-channel resting-state EEG before and after tACS and during the follow-up measurement.	Two weeks
Secondary	Corrected Amplitude Envelope Correlation (AECc)	AECc captures amplitude synchronization between different EEG channels, assessed using 64-channel resting-state EEG before and after tACS and during the follow-up measurement.	Two weeks
Secondary	Relative power	Relative power will be calculated by dividing the absolute power of the frequency band by the total absolute power in the EEG, assessed using 64-channel resting-state EEG before and after tACS and during the follow-up measurement.	Two weeks