Clinical trial NCT06285721: Delirium Treatment With Transcranial Electrical Stimulation
Official title: DELirium Treatment With Transcranial Electrical Stimulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Delirium
Keywords: electroencephalography
transcranial alternating current stimulation
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
name: HagaZiekenhuis
First posted: 2024-02-29
Enrollment: 159
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Relative delta power
timeFrame: 1 day
Secondary outcomes:
measure: Duration of delirium
timeFrame: Two weeks
measure: Severity of delirium
timeFrame: Two weeks
measure: Length of hospital stay
timeFrame: 3 months
measure: Cognitive status three months post delirium
timeFrame: 3 months
measure: Subjective sensations during treatment
timeFrame: Two weeks
measure: Average peak frequency
timeFrame: Two weeks
measure: Phase Lag Index
timeFrame: Two weeks
measure: Corrected Amplitude Envelope Correlation (AECc)
timeFrame: Two weeks
measure: Relative power
timeFrame: Two weeks
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis
state: Zuid-Holland
Study officials:
affiliation: UMC Utrecht
name: Arjen JC Slooter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: