Immersive Virtual Reality in Mechanically Ventilated Patients

• ClinicalTrials.gov Identifier: NCT03569358
• Recruitment Status: Unknown
• First Posted: June 26, 2018
• Last Update Posted: February 4, 2019
• Sponsor: Changi General Hospital
• Collaborators: BetaSight Technologies Pte Ltd; Institute for Infocomm Research
• Information provided by (Responsible Party): Jessica Quah Li Shan, Changi General Hospital

Study Description

Brief Summary:

New or worsening cognitive impairment occurs in up to 58% of survivors of critical illnesses and are long-lasting with significant disability and socioeconomic cost. There are currently no known interventions that reduce the incidence of cognitive impairment after critical illnesses. Immersive Virtual Reality (IVR) is the use of technology to create a perception of presence in a three-dimensional, computer-generated interactive simulated environment. Prior clinical studies have demonstrated potential efficacy in rehabilitation of severe traumatic brain injury.

The investigators propose a preliminary study for the evaluation of safety, tolerability, and early efficacy of immersive virtual reality for early neurocognitive stimulation in critically-ill, mechanically ventilated patients. The investigators hypothesize that the use of IVR technology for early neurocognitive simulation is safe and tolerable in these patients. This study will also evaluate whether early application of IVR in critically ill, mechanically ventilated subjects, can provide neurocognitive stimulation.

30 patients admitted to the intensive care unit for acute respiratory failure or septic shock will be evaluated for recruitment. 10 patients will be in the control group and 20 patients would have 2 sessions of IVR planned daily for a maximum of 3 days. Assessment of safety will involve monitoring for physiological derangements in heart rate, respiratory rate, pulse oximetry and blood pressure during the IVR session. Assessment of tolerability will involve monitoring for increased agitation. Assessment of early efficacy will involve evaluation of visual attention during the IVR session. 5-channel electroencephalogram would aim to detect objective changes in visual event-related potentials and the IVR headgear will incorporate eye-tracking technology.

To conclude, should IVR be feasible and safe, future interventional studies may be planned to investigate its impact on reduction in the use of sedatives, analgesia, delirium incidence and severity of cognitive impairment associated with critical illness.

Condition or disease	Intervention/treatment	Phase
Mechanical Ventilation; Virtual Reality; Delirium	Device: Immersive Virtual Reality; Device: EEG headband	Not Applicable

Detailed Description:

Advancements in the last 2 decades in the field of critical care medicine has led to an improvement in mortality of critically ill patients. This has led to interest in the long-term functional disabilities that the survivors suffer. The risks of developing cognitive dysfunction after critical illness has been associated with older age, longer duration of critical illness, hyperglycaemia, prolonged use of sedatives and analgesia, as well as delirium. The BRAIN-ICU study reported that in adults with respiratory failure and shock, the incidence of cognitive impairment at 1 year was 34% for 1.5 SD below population mean (similar to moderate traumatic brain injury) and 24% for 2.5 SD below population mean (similar to mild Alzheimer's disease). Some proposed mechanisms include cerebral hypoxia secondary to respiratory failure, cerebral inflammation and neuronal apoptosis related to sepsis, and prolonged disruption of sleep cycles. Neuronal imaging such as diffusion-tensor MRI during critical illness show diffuse hyperintense white matter changes and subsequent distant imaging studies show generalised cerebral atrophy.

Critical care societies have endorsed the use of care bundles for pain, agitation and delirium management. Few specialised centres with dedicated survivor clinics evaluate functional impairment via diagnostic investigations, physical, neurological examinations and psychological assessments, to provide personalised rehabilitation. While these initiatives have been shown to improve patient satisfaction, quality of transitional care and reduction of inappropriate emergency room visits, there are no definitive interventions that have improved cognitive outcomes.

Psychiatric co-morbidities of anxiety, depression and post-traumatic stress disorder(PTSD) have been shown to be associated with delirium and cognitive impairment after critical illness. Survivor accounts revealed a mixture of delusional and factual memories resulting in the distortion of experiences. Intensive care diaries involve the recording of significant daily events and is an attempt at systematic reconstruction of memories by medical staff, family and friends. This has been shown to reduce the incidence of PTSD after critical illness. It raises the possibility that incidence of cognitive impairment, too, may be reduced with non-pharmacological methods.

An intensive care admission involves the immersion of a patient in a foreign environment that is dominated by machines, the use of esoteric language by medical staff and persistent sleep disruption that combines deprivation of meaningful sensory stimulation with noxious sensory overload of alarms and lights. There is an unmet need for the provision of a calm, familiar environment, and deliberate neurocognitive simulation with the intention of allowing processes of thought, reasoning, memory and imagination to occur as they do in everyday life. Allowing these cognitive processes to occur may reduce the use of sedatives, delirium occurrence, and possibly cognitive impairment. Cognitive impairment after critical illness is known to decrease the rehabilitation potential of survivors, increase caregiver burden and is associated with higher utilisation of long-term healthcare resources. There is a need for interventional clinical studies that address prolonged cognitive impairment after critical illnesses.

The overall aim of the study is to improve clinical outcomes in critically ill and mechanically ventilated patients.

The primary hypothesis is that the use of an immersive virtual reality headset for early neurocognitive stimulation in critically ill, mechanically ventilated patients is safe and well tolerated (i.e., does not result in significantly increased agitation).

The primary outcome of the study would be the composite endpoint of both safety and tolerability. The immersive VA is considered as safe and tolerable if the patient does not experience any safety or tolerability events. In both arms, subjects who complete of 4 out of 4 to 6 planned sessions would be considered as having met criteria for both safety and tolerability. If 3 or less sessions were initiated, completion of 2 or more sessions would be considered for having met criteria for both safety and tolerability. The IVR intervention would be considered safe and tolerable if the difference in composite endpoint in the intervention arm is not 20% more than the control arm.

Demonstration of safety, defined as the non-occurrence of significant physiological events that require early termination of the IVR session. The use of an iVR is safe and does not cause physiological changes that require the termination of more than 2 out of 6 planned interventions.

Demonstration of tolerability, defined as: the occurrence of the event that the Richmond Agitation-Sedation Score (RASS) greater than or equal to +2 during the use of the immersive virtual reality headset and for the immediate 15 minutes after completion. The RASS score, ranging from -5 to +4, is a validated scoring system used by clinical staff to evaluate the degree of sedation and agitation of mechanically ventilated patients. A score of +2 reflects an agitated state that is characterised by frequent non-purposeful movement or presence of patient-ventilator dys-synchrony. Each subject has 6 planned interventions, completion of 4 out of 6 interventions would be considered demonstration of tolerability.

There are 2 secondary aims in this study to demonstrate early efficacy in terms of neurocognitive stimulation. One would be comparing change in the EEG data after the immersive VR sessions from the baseline, that may indicate visual attention. The hypothesis is that visual attention during the intervention can be demonstrated with EEG waveforms. The other secondary aim will be evaluation of the eye-tracking software as a potential tool for meaningful interaction.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Safety, Tolerability, and Early Efficacy of Immersive Virtual Reality for Early Neurocognitive Stimulation in the Intensive Care Unit.
• Actual Study Start Date: July 2, 2018
• Estimated Primary Completion Date: July 2, 2019
• Estimated Study Completion Date: July 2, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Virtual Reality and EEG Interventions; In the interventional arm, 20 subjects will receive twice daily sessions of immersive virtual reality for a maximum of 15 minutes, with EEG headband recording starting 5 minutes prior to and 5 minutes after the intervention, for a maximum of 4 consecutive days.	Device: Immersive Virtual Reality; The immersive virtual reality headgear used is the commercially available FOVE VR headset. It incorporates a 2560x1440 pixel display, position tracking-and eye-tracking. The headset weight 520g with adjustable velcro straps. Softwares are run via a computer connected by HDMI or USB cables.; Device: EEG headband; The EEG headband is commercially available MUSE band. It incorporates 4-channel dry electrode EEG system where data can be recorded with bluetooth connection.
Active Comparator: EEG Intervention group; In the control arm, 10 subjects would have EEG recorded for 25 mins twice daily, with a minimum of 4 hours intervening, for 3 consecutive days, with the EEG headband. There would be no immersive virtual reality sessions.	Device: EEG headband; The EEG headband is commercially available MUSE band. It incorporates 4-channel dry electrode EEG system where data can be recorded with bluetooth connection.
Active Comparator: Healthy Volunteers; At the completion of the above intensive care study recruitment, demographic data of the interventional immersive virtual reality arm would analysed to recuit 10 age-matched healthy volunteers with no known cognitive disorders or visual impairment. This is to compare study data with healthy controls. A 25 minute session consisting of 15 minutes of immersive virtual reality and 5 minutes of EEG recording with the EEG headband before and after the intervention would be performed. Eye-tracking and EEG data from these groups of patients would be compared against subjects in both arms of the study performed in the intensive care unit to investigate for exploratory differences.	Device: Immersive Virtual Reality; The immersive virtual reality headgear used is the commercially available FOVE VR headset. It incorporates a 2560x1440 pixel display, position tracking-and eye-tracking. The headset weight 520g with adjustable velcro straps. Softwares are run via a computer connected by HDMI or USB cables.; Device: EEG headband; The EEG headband is commercially available MUSE band. It incorporates 4-channel dry electrode EEG system where data can be recorded with bluetooth connection.

Outcome Measures

Primary Outcome Measures :

1. The primary outcome of the study would be the number of patients who are able to complete immersive virtual reality session meeting both safety and tolerability criteria. [ Time Frame: 4 days ]
   The IVR intervention would be considered safe and tolerable if the difference in number of subjects having a composite endpoint of both safety and tolerability end-points in the intervention arm is not 20% more than the control arm. Demonstration of safety is the composite of non-occurrence of any 4 physiological events as follows: greater than 30% variability in the heart rate; greater than 30% variability in respiratory rate; systolic blood pressure of less than 90mmHg or more than 160mmHg; pulse oximetry of less than 90%. Demonstration of tolerability is the non-occurrence of the event that Richmond Agitation-Sedation Score (RASS) greater than or equal to +2 during the intervention, sustained for more than 3 minutes.

Secondary Outcome Measures :

1. Exploratory use of EEG changes to quantify differences in attention in delirious mechanically ventilated patients. [ Time Frame: 4 days ]
   EEG data before, during and after the immersive VR sessions would be recorded and compared to subjects in the control arm and the healthy subjects group. The EEG patterns would be translated into an attention score developed by academic collaborator. The hypothesis is that visual and auditory attention during the immersive virtual reality intervention can be demonstrated with EEG signals with differences in the level of attention between subjects who have delirium as assessed by ICU-CAM scores, and those who do not have delirium. The degree of eye blinking and motion artefacts generated during the intervention may also be accurately quantified and compared between intervention and control groups.
2. Assessment of visual attention in delirious subjects using virtual-reality integrated eye-tracking software. [ Time Frame: 4 days ]
   Assessment of eye movements is a potential tool for assessment of meaningful interaction in mechanically ventilated patients. The subjects would have eye movements recorded during the immersive virtual reality interventions. These would allow identification and quantification of the presence of saccadic eye movements, velocity and duration, as well as the presence and duration of smooth pursuit, to be compared between delirious and non-delirious subjects in the interventional groups.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Patient Group

  1. Patients aged 21 to 75
  2. Both genders and all races
  3. Acute respiratory failure or septic shock as indications for critical care admission
  4. Anticipated to require mechanical ventilation for a minimum of 48 hours after enrolment
  5. GCS of E3VTM4 or more

Healthy Volunteer Group

1) Age-matched to the subjects of the interventional arm of the ICU subjects.

Exclusion Criteria:

Patient Group

1. Patients who are actively using an interactive device in the intensive care unit prior to enrolment
2. Illnesses with a terminal prognosis within 3 months
3. Prisoners and pregnant patients
4. Blind or deaf patients
5. Premorbid baseline cognitive impairment
6. Neurological diseases affecting cognition as the cause of intensive care admission including but not limited to ischaemic and haemorrhagic strokes, meningitis, encephalitis, traumatic brain injuries and status epilepticus.
7. Severe critical illness with imminent mortality
8. Critical illness requiring the use of paralytic agents
9. Use of vasopressor dose more than an equivalent of Noradrenaline 0.5 mcg/kg/min
10. Use of fractional inspired oxygen on mechanical ventilation of more than 0.8.
11. Presence of external facial, skull vault or cervical injuries, or deformities, precluding the safe application of the VR headset and EEG band.
12. Participation declined by attending intensivist.

Healthy Volunteer Group

1. Known prior neurological or neurocognitive disease.
2. Baseline heart rate more than 100 beats per minute
3. Baseline systolic blood pressure less than 100 mmHg or more than 160 mmHg
4. Respiratory failure requiring supplemental oxygen

Contacts and Locations

Contacts

Contact: Jessica LS Quah, M.B.B.S.; 65-67888833 ext 0; jessica_quah@cgh.com.sg

Contact: Xin Hui Sam; 65-67888833 ext 0; xin_hui_sam@cgh.com.sg

Locations

Singapore

Changi General Hospital; Recruiting

Singapore, Singapore, 529889

Contact: CTRU CGH 67888833

Sponsors and Collaborators

Changi General Hospital

BetaSight Technologies Pte Ltd

Institute for Infocomm Research

Investigators

• Principal Investigator: Jessica LS Quah, M.B.B.S.; Changi General Hospital

More Information

Additional Information:

Demonstration of the FOVE immersive virtual reality head-mounted display 

Demonstration of the MUSE EEG headband 

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• Responsible Party: Jessica Quah Li Shan, Associate Consultant, Changi General Hospital
• ClinicalTrials.gov Identifier: NCT03569358
• Other Study ID Numbers: 201802-00023
• First Posted: June 26, 2018
• Last Update Posted: February 4, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jessica Quah Li Shan, Changi General Hospital:

Randomised Controlled Study; Unblinded; Electroencephalogram; Feasibility

Additional relevant MeSH terms:

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders