ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12623001268639p

Ethics application status

Submitted, not yet approved

Date submitted

9/05/2023

Date registered

6/12/2023

Date last updated

6/12/2023

Date data sharing statement initially provided

6/12/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Safety and Efficacy of the Application of Photobiomodulation (PBM) on Intensive Care Unit (ICU) Patients with Acute Delirium

Scientific title

Safety and Efficacy of the Application of Photobiomodulation (PBM) on Intensive Care Unit (ICU) Patients with Acute Delirium

Secondary ID [1]

Nil known to date

Universal Trial Number (UTN)

U1111-1292-2165

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Acute delirium

Condition category

Condition code

Neurological

Other neurological disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

There is no gold standard treatment for delirium. Its presentation in people admitted to the Intensive Care Unit (ICU) is complex and it complicates treatment of other conditions requiring ICU admission. ICU patients with acute delirium can be a danger to themselves and others. Presence of delirium confers an adverse prognosis for ICU patients, and management of delirium when it occurs is largely supportive. There is an urgent need for the exploration of new treatment modalities to manage acute delirium in critically ill patients. One such alternative is photobiomodulation (PBM) therapy which is the use of specific wavelengths of light to induce activation of the mitochondrial electron transport chain of nerve cells and to impact cerebral blood flow.
Primary aim: To determine if the pre-defined PBM treatment protocol delivered using a proprietary device (Neuronic 1070) influences the clinical (QEEG) presentation of acute delirium in patients admitted to ICU.
Secondary aim: To determine if there are any adverse effects from the PBM treatment protocol.

Procedures, activities, and/or processes to be used (including enabling or support activities):
To address the primary aim we will assess changes in Quantitative EEG (QEEG) before and after implementation of the treatment protocol.
To address the secondary aim we will:
- assess changes in physiological parameters including Heart Rate Variability (HRV; weekly), Blood Pressure and Heart Rate (HR) before and after each application of the treatment;
- collect nursing observations of restlessness in the period immediately before and after each application;
- collate pathology results routinely collected daily in ICU (including electrolytes, urea and creatinine, liver function tests, full blood count, and blood sugar levels); and
- assess safety and tolerability of the treatment protocol.

Who will deliver the intervention and if relevant, their expertise?
The intervention will be delivered under medical (intensivist) supervision by intensive care nursing and/or physiotherapy staff. Staff likely to be applying the intervention will be trained in the safe application of the device, and its removal.

The mode of delivery and whether it will be provided individually or in a group:
The intervention will be applied in person by intensive care staff directly to individual eligible and consented participants.

Number of times the intervention will be delivered and over what period of time (number of sessions, the schedule, and duration, intensity, or dose):
The intervention is delivered using the Neuronic 1070 brain photobiomodulation helmet. The treatment protocol will titrate PBM up to 20 minutes twice daily in a stepwise daily exposure progression (3-6-9-12-16-20 min) thus reducing likelihood of overstimulation reactions. A set of 5 x pre-determined light stimulation protocols with different pulse rates, and intensity variables will be used daily on week days for 1 month or for the duration of ICU admission, whichever is shorter. A pulse frequency of light at 10Hz will stimulate EEG Alpha wave production through the process of neural entrainment and so supporting increased parasympathetic tone. Dosing will be twice daily Monday to Friday, with the first dose commencing after the commencement of the morning nursing staff shift (approximately 8am) and the second dose 6 hours later.
Each participant will receive an initial light sensitivity test, otherwise called Protocol 1. A light sensitivity test is necessary to understand whether a participant is sensitive to photonic energy. Patients' first use of PBM (i.e., Protocol 1) starts at 3 minutes duration with 75% intensity and pulsing frequency at 10Hz. A pulse frequency of light at 10Hz will stimulate EEG Alpha production through the process of neural entrainment and so supports increased parasympathetic tone. Should no perturbation be noted, the participant will advance to a treatment protocol.
The first consented patient will be treated with and continue with Protocol 2. The second consented participant will be treated with and continue with Protocol 3. The third participant who enters the study will receive Protocol 4, and the fourth participant will receive Protocol 5. Each subsequent participant will follow in the same manner (wherein the fifth participant will receive Protocol 2, sixth participant will receive Protocol 3 and so on until all participants have been recruited).
Treatment will be applied to the whole of the cranium to irradiate all brain networks. Each treatment protocol consists of the same treatment and rest times (3 minutes of treatment applied twice in the same session) with 10 minutes rest in between. The first 3-minute treatment is applied at 8Hz, and the second 3-minute treatment is applied at 10Hz. The intensity of applied photonic energy is lowest during Protocol 2 (at 25% and 50%) and is gradually increased in each subsequent protocol (up to 100% for each 3-minute treatment in Protocol 5). By titrating the applied dose by adjusting the percentage intensity, we hope to detect which dose may have the greatest brain responsiveness for reducing the behavioural signs of delirium.
Adherence to the intervention protocols will be monitored by audit of nursing bedside care records.

The location where the intervention occurs:
The Mater Adult Intensive Care Service, South Brisbane (either the Mater Hospital Brisbane (Salmon Building) Intensive Care Unit, or the Mater Private Hospital Brisbane Intensive Care Unit).

Intervention code [1]

Treatment: Devices

Comparator / control treatment

No control group.
Within subject measures of change in the different protocols will be made by comparing baseline (pre-intervention) measure of QEEG and the post-intervention QEEG recording.
As this is an exploratory study, we will review the within-subject results at the end of the study, to decide whether and how to advance to the next stage of research.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Change in quantitative electroencephalography (QEEG) to determine cortical electrical activity of brainwaves (beta, alpha, theta and delta).

Timepoint [1]

Once at: Baseline prior to commencement of intervention.
Once more: At end of intervention phase to assess for any changes.

Secondary outcome [1]

Confusion Assessment Method for ICU (CAM-ICU) to determine effect of transcranial PBM on clinical status of diagnosed acute delirium in intensive care unit.

Timepoint [1]

Baseline for diagnostic purposes.
Daily until intervention terminated (to determine if change in clinical status of delirium).

Secondary outcome [2]

Heart rate variability (HRV) via 5-minute ECG recording to understand potential effects or side effects of transcranial PBM on autonomic nervous system activity.

Timepoint [2]

Baseline
End of each week for 4 weeks (or sooner, if PBM intervention terminated).

Secondary outcome [3]

Blood pressure (BP) measured by sphygmomanometer to understand potential effects or side effects of transcranial PBM on autonomic nervous system activity.

Timepoint [3]

Baseline prior to commencement of PBM intervention.
Daily thereafter (before and after application) until intervention terminated.

Secondary outcome [4]

To assess tolerability of transcranial PBM application, nursing observations of restlessness in period immediately before, during and after each PBM application. Nursing observations are recorded at the ICU bedside during each shift. The nursing notes will be retrospectively audited.

Timepoint [4]