The aim of the study is to investigate whether standardized or personalized tACS induces EEG changes indicative of delirium reversal (primary outcome) or reduces the duration and/or severity of delirium (secondary outcome) compared to sham treatment…
ID
Source
Brief title
Condition
- Deliria (incl confusion)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To study the effects of tACS treatment on delirium, our two primary objectives
are as follows:
I. To investigate whether one session of standardized tACS reduces the relative
delta power observed in delirium, measured using EEG.
II. To investigate whether one session of personalized tACS, based on a
computational model and virtual trial using EEG as input, reduces the relative
delta power in patients with delirium, measured using EEG.
The two main objectives of the study share the same outcome variable, namely
relative delta power, measured immediately before and after the application of
tACS or sham stimulation using a 64-channel EEG. Relative delta power has been
chosen as the primary study parameter because delirium is consistently
associated with increased delta EEG activity. As oscillatory synchronization
can have cross-frequency effects, we hypothesize that tACS applied within the
alpha frequency range improves functional connectivity, leading to reduced
relative delta power.
Secondary outcome
The aim of the pilot study is to investigate whether the tACS treatment can be
safely applied to, and tolerated sufficiently by, patients with delirium.
Outcome measures include: the percentage of completed first stimulation
sessions, increase in care needs within the first hour after tACS, and duration
of delirium.
Secondary outcomes of the main study include: severity of delirium, duration of
delirium, length of hospitalization, cognitive ability three months after tACS
treatment, difference in effect between standardized and personalized tACS,
changes in power and functional connectivity measured using EEG, subjective
expectations and evaluations of tACS as a treatment for delirium and the effect
of cumulative tACS sessions.
Background summary
Delirium, characterized by acute confusion and disturbances in cognition and
perception, prolongs hospital stays, increases healthcare costs, and leads to
long-term cognitive decline. Currently, there is no treatment that reduces the
duration or severity of delirium. Delirium is characterized by a diffuse
oscillating slowing of the electroencephalogram (EEG), including a pronounced
loss of alpha activity and an increased relative delta power. Furthermore,
functional connectivity between brain regions is reduced during delirium.
Taking this into consideration, transcranial alternating current stimulation
(tACS) is a potential treatment that directly addresses the brain dysfunction
observed in delirium. Because tACS can improve multiple domains of cognition,
including attention, it could be an effective treatment for delirium. In this
study, we aim to investigate whether tACS results in normalization of the EEG
in individuals with delirium. Additionally, we want to examine whether
different approaches of tACS, standardized or personalized using EEG data as
input, are effective compared to sham treatment.
Study objective
The aim of the study is to investigate whether standardized or personalized
tACS induces EEG changes indicative of delirium reversal (primary outcome) or
reduces the duration and/or severity of delirium (secondary outcome) compared
to sham treatment. Additionally, we are interested in exploring the safety and
tolerability of tACS as a treatment for delirium, which we are investigating
through a pilot study as an integral component of the main study.
Study design
We will conduct a double-blind, randomized, sham-controlled, multicenter study
to investigate the effectiveness of standardized and personalized tACS in
patients with delirium. Participants will be randomized in two steps between
standardized and personalized tACS, and then active or sham treatment. This
randomization results in a 1:1:1 allocation between active standardized
treatment, active personalized treatment, and sham treatment. During the
initial months of study inclusion, personalized treatment will not be
available, and randomization will occur between active standard treatment and
sham treatment, with the first 30 patients being included as part of a pilot
study to assess the tolerability of tACS in delirium. When the pilot study is
completed and personalized treatment becomes available (expected in Q2-Q3
2024), randomization weights will be calculated to achieve a 1:1:1 allocation.
EEG measurements will be conducted immediately before and after the first
stimulation session. Active tACS or sham treatment will be applied once daily
for a maximum of 14 days, until delirium has resolved or until discharge from
the hospital. During treatment, the presence and severity of delirium will be
monitored daily. The treatment phase will conclude with a final visit,
including a follow-up EEG. Three months after the study, cognitive status will
be assessed using a validated telephone interview.
Intervention
Patients will receive tACS consisting of 2 mA (peak-to-peak) stimulation
delivered for 30 minutes, using two 5x5 cm electrodes placed under a standard
64-channel EEG cap, for a maximum of 14 days. For the standardized tACS
treatment, the frequency of tACS will be in the alpha range (10 Hz), and
electrodes will be positioned over the frontal and occipito-parietal regions of
the head. In contrast, the stimulation frequency and electrode placement in
personalized tACS treatment will vary depending on the most optimal parameters
determined by a computational model.
The sham treatment will consist of a 30-second ramp-up to 60 seconds of 10 Hz
tACS, followed by a 30-second ramp-down, totaling 120 seconds of stimulation,
for a maximum of 14 days.
Study burden and risks
All measurements in this study are non-invasive. Participants may temporarily
experience mild tingling or itching under the electrodes during stimulation, or
mild headache and fatigue shortly after stimulation. The proposed tACS protocol
is considered safe according to the latest published international safety
guidelines. All participants have been screened for their relevant medical
history and contraindications for tACS. No serious or persistent side effects
are expected during this study as a result of the tACS intervention, and
therefore, the risks to the patients are considered low to very low. The visits
require an additional time commitment for questionnaires, EEG data recording,
and tACS stimulation. However, because these visits are conducted while the
patient is hospitalized, the burden on the participants is considered low.
Considering the negative effects of delirium on (long-term) functioning and the
fact that there is currently no effective treatment available, the benefit of a
potentially new treatment targeting the underlying brain dysfunction of
delirium is considered high.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
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 valid delirium screening assessment (e.g. coma, deaf,
blind) or inability to speak the Dutch or English language.
Patients in 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).
Standard contra-indications for tACS (history of serious head trauma or brain
surgery; large or ferromagnetic metal parts in the head (except for a dental
wire);
implanted cardiac pacemaker or neurostimulator; skin diseases or inflammations;
epilepsy)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL84043.041.23 |