Transcranial Alternating Current Stimulation on Patients with Delirium and Critical Illness (DeliTACS) (DeliTACS)

Transcranial Alternating Current Stimulation on Patients with Delirium and Critical Illness: a Randomized, Controlled, Double Blind, Proof-of-concept Pilot Study

The goal of this clinical trial is to learn if transcranial alternating current stimulation can shorten the duration of delirium in intensive care setting. The main question it aims to answer:

• Is it possible to shorten the duration of delirium with transcranial alternating current stimulation?

Researchers will compare experimental treatment to sham.

Participants will receive experimental or sham treatment on maximum of two days depending on their delirium status. Duration of delirium is recorded and reported as "days alive and free of delirium".

Study Overview

• Status: Recruiting
• Conditions: Delirium
• Intervention / Treatment: Device: Transcranial alternating current stimulation (TACS); Device: Sham TACS

Detailed Description

Delirium is an acute-onset brain dysfunction related to extensive surgery or critical illness that leads to altered mental status and cognitive deficits. Delirium is associated with an increased length of stay in the ICU, cost of care, excessive mortality, and long-term cognitive and functional impairment. Although numerous prophylactic methods have been proposed, currently, no pharmacological or non-pharmacological methods are clinically effective. Patients with delirium have altered electroencephalography (EEG) findings among which most important are general slowing of EEG frequencies and dysconnectivity. Faster EEG frequencies, especially alpha-, beta-, and gamma-bands, are correlated with higher cognitive functions, such as memory and orientation. Transcranial alternating current stimulation (TACS) is a novel, noninvasive brain stimulation technology that cab modulate EEG frequencies by entraining of endogenous brain oscillations in response to exogenous stimuli. TACS has been shown to improve episodic memory, orientation, and cholinergic dysfunction in patients with Alzheimer's disease. TACS also increases alpha and gamma frequencies in EEG, and an increase in these frequencies is associated with the improvement of clinical symptoms. TACS has been shown to target key components of delirium pathophysiology, such as slowing of EEG frequencies and cholinergic dysfunction. Thus, we hypothesized that TACS could shorten the duration of delirium and decrease cognitive decline. We aim to test this hypothesis in a double-blind randomized trial and assess the effect of TACS on duration of delirium, EEG, biomarkers and long-term cognition.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ville Ihalainen; Phone Number: +358 447176388; Email: ville.ihalainen@pshyvinvointialue.fi

Study Locations

• Finland
  • Kuopio, Finland
    • Recruiting
    • Kuopio University Hospital
    • Contact: Ville Ihalainen, MD; Phone Number: +358447176388; Email: ville.ihalainen@pshyvinvointialue.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Delirium in intensive care and duration of delirium for more than 24 hours. Delirium is defined as 4 or more points on ICDSC and -1 or more points on RASS.

Exclusion Criteria:

• Under 18 years of age, pregnancy, delirium tremens, epilepsy or history of seizures any time before first trial intervention, active psychotic disease, infection of central nervous system, acute intoxication, traumatic brain injury, stroke, intracranial bleeding and implanted electronic devices.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcranial alternating current stimulation (TACS); Experimental intervention is alternating sinusoidal current at frequency of 40 Hz applied for 60 min through a pair of saline-soaked surface sponge electrodes. One electrode is placed with the center over Pz position according to the 10-20 international EEG coordinates (an area overlying the medial parietal cortex and the precuneus) and the other over the right deltoid muscle.	Device: Transcranial alternating current stimulation (TACS); Transcranial alternating sinusoidal current at frequency of 40 Hz applied for 60 min through a pair of saline-soaked surface sponge electrodes.
Sham Comparator: Sham TACS; The same electrodes are connected to the patient as in trial intervention. In sham treatment, a few seconds of actual current is provided and then the device automatically turns off. This is to ensure that patients cannot distinguish between real and sham treatments based on possible tingling of skin when starting the electrical current.	Device: Sham TACS; Sham treatment with few seconds of actual electrical current and same electrode configuration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days alive and free of delirium or coma	Days alive and free of delirium or coma	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker profile	Concentrations of neurofilament light (nfl), glial fibrillary acid (gfap) and plasma tau (ptau) on days 0, 2 and 4	4 days
EEG changes	EEG Spectral power	2 days
CERAD	CERAD test (Consortium to Establish a Registry for Alzheimer's Disease)	3 and 12 months
TMT test A	Trail Making Test A	3 and 12 months
TMT test B	Trail Making Test B	3 and 12 months
Short latency inhibition	Measurement of brain cholinergic function by short latency inhibition with transcranial magnetic stimulation	3 and 12 months

Collaborators and Investigators

• Sponsor: Kuopio University Hospital
• Investigators: Principal Investigator: Stepani Bendel, Kuopio University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 14, 2024

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Delirium; Intensive care; Brain stimulation; Tacs
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Delirium; Critical Illness
• Other Study ID Numbers: KUH507T056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No