Mechanical VentilationNCT03569358
Immersive Virtual Reality in Mechanically Ventilated Patients
A study testing Immersive Virtual Reality and EEG headband in people with Mechanical Ventilation and Virtual Reality, run by Changi General Hospital at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Mechanical Ventilation, Virtual Reality, Delirium
- What is being tested?
- Immersive Virtual Reality and EEG headband
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSingapore
- Study dates
- 2 Jul 2018to 2 Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patient Group
- Patients aged 21 to 75
- Both genders and all races
- Acute respiratory failure or septic shock as indications for critical care admission
- Anticipated to require mechanical ventilation for a minimum of 48 hours after enrolment
- GCS of E3VTM4 or more
- Healthy Volunteer Group
- 1) Age-matched to the subjects of the interventional arm of the ICU subjects.
Who cannot join
- Patient Group
- Patients who are actively using an interactive device in the intensive care unit prior to enrolment
- Illnesses with a terminal prognosis within 3 months
- Prisoners and pregnant patients
- Blind or deaf patients
- Premorbid baseline cognitive impairment
Show all 18Show fewer
- 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.
- Severe critical illness with imminent mortality
- Critical illness requiring the use of paralytic agents
- Use of vasopressor dose more than an equivalent of Noradrenaline 0.5 mcg/kg/min
- Use of fractional inspired oxygen on mechanical ventilation of more than 0.8.
- Presence of external facial, skull vault or cervical injuries, or deformities, precluding the safe application of the VR headset and EEG band.
- Participation declined by attending intensivist.
- Healthy Volunteer Group
- Known prior neurological or neurocognitive disease.
- Baseline heart rate more than 100 beats per minute
- Baseline systolic blood pressure less than 100 mmHg or more than 160 mmHg
- Respiratory failure requiring supplemental oxygen
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
Changi General Hospital
Singapore, 529889
CTRU CGH, 67888833
About this study
Official title: Safety, Tolerability, and Early Efficacy of Immersive Virtual Reality for Early Neurocognitive Stimulation in the Intensive Care Unit.
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.
Read more
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.
Read the 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.
- Conditions
- Mechanical Ventilation, Virtual Reality, Delirium
- Being tested
- Immersive Virtual Reality, EEG headband
- Keywords
- Randomised Controlled Study, Unblinded, Electroencephalogram, Feasibility
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immersive Virtual RealityDevice
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.
EEG headbandDevice
The EEG headband is commercially available MUSE band. It incorporates 4-channel dry electrode EEG system where data can be recorded with bluetooth connection.
| Study group | Role | What they receive |
|---|---|---|
| Virtual Reality and EEG Interventions | Experimental | 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. Receives: Device: Immersive Virtual Reality; Device: EEG headband |
| EEG Intervention group | Active comparator | 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. Receives: Device: EEG headband |
| Healthy Volunteers | Active comparator | 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. Receives: Device: Immersive Virtual Reality; Device: EEG headband |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: 4 days
Secondary outcomes (2)
Exploratory use of EEG changes to quantify differences in attention in delirious mechanically ventilated patients.
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.
Measured: 4 days
Assessment of visual attention in delirious subjects using virtual-reality integrated eye-tracking software.
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.
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2018
- Study start2 Jul 2018
- Primary completion2 Jul 2019 (estimated)
- Study completion2 Jul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Mechanical VentilationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changi General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- BetaSight Technologies Pte Ltd, Institute for Infocomm Research
- Responsible party
- Principal investigator, Jessica Quah Li Shan, Changi General Hospital
- Investigators
- Jessica LS Quah, M.B.B.S., Principal investigator, Changi General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03569358
- Sponsor's protocol ID
- 201802-00023
- Status last verified
- Feb 2019
- First submitted
- 22 May 2018
- Last updated
- 4 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zimmerman JE, Kramer AA, Knaus WA. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care. 2013 Apr 27;17(2):R81. doi: 10.1186/cc12695.
PubMed 23622086Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr 2;311(13):1308-16. doi: 10.1001/jama.2014.2637.
PubMed 24638143Needham DM, Davidson J, Cohen H, Hopkins RO, Weinert C, Wunsch H, Zawistowski C, Bemis-Dougherty A, Berney SC, Bienvenu OJ, Brady SL, Brodsky MB, Denehy L, Elliott D, Flatley C, Harabin AL, Jones C, Louis D, Meltzer W, Muldoon SR, Palmer JB, Perme C, Robinson M, Schmidt DM, Scruth E, Spill GR, Storey CP, Render M, Votto J, Harvey MA. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med. 2012 Feb;40(2):502-9. doi: 10.1097/CCM.0b013e318232da75.
PubMed 21946660Shao C, Gu L, Mei Y, Li M. [Analysis of the risk factors of cognitive impairment in post-intensive care syndrome patient]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 Aug;29(8):716-720. doi: 10.3760/cma.j.issn.2095-4352.2017.08.009. Chinese.
PubMed 28795670Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.
PubMed 24088092Jackson JC, Ely EW. Cognitive impairment after critical illness: etiologies, risk factors, and future directions. Semin Respir Crit Care Med. 2013 Apr;34(2):216-22. doi: 10.1055/s-0033-1342984. Epub 2013 May 28.
PubMed 23716312Jackson JC, Hopkins RO, Miller RR, Gordon SM, Wheeler AP, Ely EW. Acute respiratory distress syndrome, sepsis, and cognitive decline: a review and case study. South Med J. 2009 Nov;102(11):1150-7. doi: 10.1097/SMJ.0b013e3181b6a592.
PubMed 19864995Trogrlic Z, van der Jagt M, Bakker J, Balas MC, Ely EW, van der Voort PH, Ista E. A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care. 2015 Apr 9;19(1):157. doi: 10.1186/s13054-015-0886-9.
PubMed 25888230Khan BA, Lasiter S, Boustani MA. CE: critical care recovery center: an innovative collaborative care model for ICU survivors. Am J Nurs. 2015 Mar;115(3):24-31; quiz 34, 46. doi: 10.1097/01.NAJ.0000461807.42226.3e.
PubMed 25674682Kapfhammer HP, Rothenhausler HB, Krauseneck T, Stoll C, Schelling G. Posttraumatic stress disorder and health-related quality of life in long-term survivors of acute respiratory distress syndrome. Am J Psychiatry. 2004 Jan;161(1):45-52. doi: 10.1176/appi.ajp.161.1.45.
PubMed 14702249Jackson JC, Pandharipande PP, Girard TD, Brummel NE, Thompson JL, Hughes CG, Pun BT, Vasilevskis EE, Morandi A, Shintani AK, Hopkins RO, Bernard GR, Dittus RS, Ely EW; Bringing to light the Risk Factors And Incidence of Neuropsychological dysfunction in ICU survivors (BRAIN-ICU) study investigators. Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med. 2014 May;2(5):369-79. doi: 10.1016/S2213-2600(14)70051-7. Epub 2014 Apr 7.
PubMed 24815803Roberts BL, Rickard CM, Rajbhandari D, Reynolds P. Factual memories of ICU: recall at two years post-discharge and comparison with delirium status during ICU admission--a multicentre cohort study. J Clin Nurs. 2007 Sep;16(9):1669-77. doi: 10.1111/j.1365-2702.2006.01588.x.
PubMed 17727586Garrouste-Orgeas M, Coquet I, Perier A, Timsit JF, Pochard F, Lancrin F, Philippart F, Vesin A, Bruel C, Blel Y, Angeli S, Cousin N, Carlet J, Misset B. Impact of an intensive care unit diary on psychological distress in patients and relatives*. Crit Care Med. 2012 Jul;40(7):2033-40. doi: 10.1097/CCM.0b013e31824e1b43.
PubMed 22584757Kamdar BB, Huang M, Dinglas VD, Colantuoni E, von Wachter TM, Hopkins RO, Needham DM; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Joblessness and Lost Earnings after Acute Respiratory Distress Syndrome in a 1-Year National Multicenter Study. Am J Respir Crit Care Med. 2017 Oct 15;196(8):1012-1020. doi: 10.1164/rccm.201611-2327OC.
PubMed 28448162O'Connor MF, Nunnally ME. Expect the unexpected: clinical trials are key to understanding post-intensive care syndrome. Crit Care. 2013 Jun 12;17(3):149. doi: 10.1186/cc12725.
PubMed 23759107
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, and Early Efficacy of Immersive Virtual Reality for Early Neurocognitive Stimulation in the Intensive Care Unit.
- ClinicalTrials.gov ID
- NCT03569358
- Acronym / sponsor ID
- 201802-00023
- Conditions
- Mechanical Ventilation, Virtual Reality, Delirium
- Keywords
- Randomised Controlled Study, Unblinded, Electroencephalogram, Feasibility
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Changi General HospitalUniversity, hospital or other
- Collaborators
- BetaSight Technologies Pte Ltd, Institute for Infocomm Research
- Study start
- 2 Jul 2018 (actual)
- Primary completion
- 2 Jul 2019 (estimated)
- Study completion
- 2 Jul 2019 (estimated)
- First posted
- 26 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Virtual Reality and EEG Interventions | Experimental | Device: Immersive Virtual Reality, Device: EEG headbandIn 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. |
| EEG Intervention group | Active comparator | Device: EEG headbandIn 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. |
| Healthy Volunteers | Active comparator | Device: Immersive Virtual Reality, Device: EEG headbandAt 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. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient Group
- Healthy Volunteer Group
- 1) Age-matched to the subjects of the interventional arm of the ICU subjects.
Key exclusion criteria (18 listed)
- Patient Group
- Patients who are actively using an interactive device in the intensive care unit prior to enrolment
- Illnesses with a terminal prognosis within 3 months
- Prisoners and pregnant patients
- Blind or deaf patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immersive Virtual RealityThe 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 | Healthy Volunteers, Virtual Reality and EEG Interventions |
| EEG headbandThe EEG headband is commercially available MUSE band. It incorporates 4-channel dry electrode EEG system where data can be recorded with bluetooth connection. | Device | EEG Intervention group, Healthy Volunteers, Virtual Reality and EEG Interventions |
Primary outcome
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.
2 secondary outcomes
Exploratory use of EEG changes to quantify differences in attention in delirious mechanically ventilated patients.
Time frame: 4 days
Assessment of visual attention in delirious subjects using virtual-reality integrated eye-tracking software.
Time frame: 4 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2019.
- Background: PubMed 23622086Zimmerman JE, Kramer AA, Knaus WA. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care. 2013 Apr 27;17(2):R81. doi: 10.1186/cc12695.
- Background: PubMed 24638143Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr 2;311(13):1308-16. doi: 10.1001/jama.2014.2637.
- Background: PubMed 21946660Needham DM, Davidson J, Cohen H, Hopkins RO, Weinert C, Wunsch H, Zawistowski C, Bemis-Dougherty A, Berney SC, Bienvenu OJ, Brady SL, Brodsky MB, Denehy L, Elliott D, Flatley C, Harabin AL, Jones C, Louis D, Meltzer W, Muldoon SR, Palmer JB, Perme C, Robinson M, Schmidt DM, Scruth E, Spill GR, Storey CP, Render M, Votto J, Harvey MA. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med. 2012 Feb;40(2):502-9. doi: 10.1097/CCM.0b013e318232da75.
- Background: PubMed 28795670Shao C, Gu L, Mei Y, Li M. [Analysis of the risk factors of cognitive impairment in post-intensive care syndrome patient]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 Aug;29(8):716-720. doi: 10.3760/cma.j.issn.2095-4352.2017.08.009. Chinese.
- Background: PubMed 24088092Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.
- Background: PubMed 23716312Jackson JC, Ely EW. Cognitive impairment after critical illness: etiologies, risk factors, and future directions. Semin Respir Crit Care Med. 2013 Apr;34(2):216-22. doi: 10.1055/s-0033-1342984. Epub 2013 May 28.
- Background: PubMed 19864995Jackson JC, Hopkins RO, Miller RR, Gordon SM, Wheeler AP, Ely EW. Acute respiratory distress syndrome, sepsis, and cognitive decline: a review and case study. South Med J. 2009 Nov;102(11):1150-7. doi: 10.1097/SMJ.0b013e3181b6a592.
- Background: PubMed 25888230Trogrlic Z, van der Jagt M, Bakker J, Balas MC, Ely EW, van der Voort PH, Ista E. A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care. 2015 Apr 9;19(1):157. doi: 10.1186/s13054-015-0886-9.
- Background: PubMed 25674682Khan BA, Lasiter S, Boustani MA. CE: critical care recovery center: an innovative collaborative care model for ICU survivors. Am J Nurs. 2015 Mar;115(3):24-31; quiz 34, 46. doi: 10.1097/01.NAJ.0000461807.42226.3e.
- Background: PubMed 14702249Kapfhammer HP, Rothenhausler HB, Krauseneck T, Stoll C, Schelling G. Posttraumatic stress disorder and health-related quality of life in long-term survivors of acute respiratory distress syndrome. Am J Psychiatry. 2004 Jan;161(1):45-52. doi: 10.1176/appi.ajp.161.1.45.
- Background: PubMed 24815803Jackson JC, Pandharipande PP, Girard TD, Brummel NE, Thompson JL, Hughes CG, Pun BT, Vasilevskis EE, Morandi A, Shintani AK, Hopkins RO, Bernard GR, Dittus RS, Ely EW; Bringing to light the Risk Factors And Incidence of Neuropsychological dysfunction in ICU survivors (BRAIN-ICU) study investigators. Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med. 2014 May;2(5):369-79. doi: 10.1016/S2213-2600(14)70051-7. Epub 2014 Apr 7.
- Background: PubMed 17727586Roberts BL, Rickard CM, Rajbhandari D, Reynolds P. Factual memories of ICU: recall at two years post-discharge and comparison with delirium status during ICU admission--a multicentre cohort study. J Clin Nurs. 2007 Sep;16(9):1669-77. doi: 10.1111/j.1365-2702.2006.01588.x.
- Demonstration of the FOVE immersive virtual reality head-mounted displayLink provided by the sponsor.
- Demonstration of the MUSE EEG headbandLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Mechanical Ventilation
Not yet recruitingObservational study
Early Switch in Moderate ARDS
Acute Respiratory Distress Syndrome (ARDS)
RecruitingPhase 3
Optimizing Pain Treatment in Children On Mechanical Ventilation
Mechanical Ventilation, Pediatric Acute Respiratory Failure
Not yet recruitingObservational study
Predicting the Need for Invasive Mechanical Ventilation Using Different Risk Scores
High Flow Oxygen Therapy, Non Invasive Ventilation (NIV)
Not yet recruiting
The Hemodynamic Impact of High-frequency Oscillatory Ventilation and Periodic Sighs in Preterm Infants
Preterm, Respiratory Distress Syndrome in Premature Infant
Not yet recruitingObservational study
Detecting Early Weaning-induced Pulmonary Oedema Using Lung Impedance Negative Trend During Spontaneous Breathing Trials
Weaning-induced Pulmonary Edema, Mechanical Ventilation Weaning
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jessica LS Quah, M.B.B.S. principal investigator
Changi General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Immersive Virtual Reality and EEG headband in people with Mechanical Ventilation and Virtual Reality, run by Changi General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jessica LS Quah, M.B.B.S. (65-67888833 ext. 0, jessica_quah@cgh.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03569358, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2019.