Feasibility and Acceptability of ReCognitionVR-based Cognitive Stimulation in Surgical Patients
Phase: NA
Conditions: Surgery, Delirium, Delirium, Post-Operative
Sponsor: The Methodist Hospital Research Institute

 
 
Study Title: Feasibility and Acceptability of ReCognitionVR-Based  
Cognitive Stimulation in Surgical Patients 
 
PI: Dr. Hina Faisal 
Department of Surgery 
Houston Methodist Hospital 
 
 
 
NCT Number: NCT06232317 
 
 
Protocol Date: August 8, 2023 

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 1 of 21
HMRI Basic Protocol Template v23Mar2023
PROTOCOL TITLE:
Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
PRINCIPAL INVESTIGATOR 
Hina Faisal, MD
Houston Methodist Hospital/Department of Surgery
CO-INVESTIGATORS/ COLLABORATORS:
Jiaqiong Susan Xu, PhD
Houston Methodist Hospital TMC/ Biostatistics in Medicine
Faisal Masud, MD, FCCP, FCCM
Houston Methodist Hospital TMC/ Clinical Anesthesiology & Critical Care
SPONSOR / FUNDING AGENCY 
Houston Methodist Hospital 
National Institute of Health (NIH)/National Institute on Aging 
VERSION NUMBER/DATE 
v.1: 08 August 2023 
REVISION HISTORY
Revision #
Version Date
Summary of Changes
Consent Change
(Yes/No)
1. Study Summary 
Virtual reality (VR) imitates reality by creating an artificial three-dimensional (3-D) environment 
using computing technology or software. A virtual environment (VE) is created using this 
software with a headset, which cognitively stimulates the user's brain to think they are in an 
artificial world. Creating a VE allows flexibility and measurement of different types of stimuli 
while recording the various responses provided by users in the controlled VE. VR strengthens the 
brain's ability to focus, learn, and retain experience. VR for attention deficit disorders has been 
reported to have promising results. We followed in similar footsteps and designed and 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 2 of 21
HMRI Basic Protocol Template v23Mar2023
developed a novel, 3D simulated software platform prototype called ReCognition VR to provide 
VR-based cognitive exercises. 
A feasibility clinical trial conducted by our group tested the ReCognitionVR cognitive 
interventions on older and young healthy volunteers (Appendix A. Final Study Report). The 
results of this study showed that ReCognitionVR-based cognitive exercises were feasible, 
acceptable, and tolerable by older healthy subjects.  In stage 2 of our research study, we want to 
evaluate the safety, feasibility, acceptability, and tolerability of VR-based cognitive exercises in 
60-year-old or older patients following abdominal surgery admitted to the surgical floor at 
Houston Methodist Hospital (HMH). Our premise is that VR-based cognitive stimulation software 
will allow the controlled delivery of structured cognitive exercises focusing on orientation, 
attention, memory, and executive functions. The system will allow customized frequency and 
duration of cognitive exercises based on the users' difficulty level in a delightfully relaxed- 
environment with beach wave sounds.  
Hypothesis:
We will test the hypothesis that the test population will find ReCognitionVR-based cognitive 
exercise safe, feasible, acceptable, and tolerable. 
2. Purpose of the Study / Objectives 
This study aims to assess the feasibility, acceptability, and safety of using ReCognitionVR-based 
software in older surgical patients. Results from this study will be used to inform the design of a 
future study in critically ill hospitalized patients at risk for delirium.
The question that drives this study is:
In surgical floor patients, what is the safety and feasibility of using the ReCognition VR-based 
cognitive exercise, and what is the acceptability and tolerability of the exercise?
OBJECTIVES AND ENDPOINTS
OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
Primary
The primary objective of this 
study is the safety of VR-based 
cognitive stimulation exercises 
for older surgical patients. 
The primary endpoint is the 
proportion of treatment-
emergent adverse events (TEAE) 
in each group (experimental and 
control).
1. To assess tolerability 
of ReCognitionVR-based 
cognitive stimulation 
exercises.
2. Adverse events (e.g., 
cybersickness) will 
assess tolerability 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 3 of 21
HMRI Basic Protocol Template v23Mar2023
OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
during engagement 
through exercise 
provided by 
ReCognitionVR games.
Secondary
The secondary objectives are

To assess the changes in vital 
signs during the exercise

To assess change in vital 
signs at the end of the 
exercise

To assess the feasibility of 
VR-based cognitive 
stimulation exercises in older 
surgical patients.

To determine the 
acceptability of VR-based 
cognitive stimulation 
exercises
The secondary endpoints are:
1. Mean change from pre 
to 10 minutes:
a. Pulse oximetry oxygen 
saturation (SpO2)
b. Respiratory rate (RR)
c.
Blood pressure (BP)
2. Mean change from pre 
to end of VR session:
a. SpO2
b. RR
c.
BP

using the ReCognitionVR-
based cognitive exercise for 
20 minutes by 70% of 
enrolled participants.

the proportion of 
participants with a System 
Usability Scale (SUS) score 
>35.
Knowing the change in 
these biometric 
measures will assist in 
designing future 
investigations of 
patients at risk of 
delirium.
It is essential to know if 
participants can 
complete the exercise 
since an incomplete 
experience will prohibit 
the assessment of the 
other variables to be 
measured. 
Successful 
implementation 
depends on the 
acceptability of the 
intervention and is one 
of the main factors 
considered before 
adopting and 
implementing 
computerized cognitive 
software.
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 4 of 21
HMRI Basic Protocol Template v23Mar2023
OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS

To determine the accuracy of 
VR-games

Technical difficulty with VR 
software 

the proportion of 
participants who complete 
the game without any user 
errors. 

Number of attempts to 
complete the game. 

 Number of software and 
device re-starts and re-sets. 
Accuracy is an essential 
variable in assessing the 
attention of the study 
subject. 
Attention is a 
prominent cognitive 
domain involved in 
delirium. 
Important to upgrade 
or incorporate 
advanced VR software.
Exploratory 
Exploratory outcome to report 
the episode of delirium 

Confusion Assessment 
Method (CAM) tool 
(Appendix B)6 or 4 A’s Test 
score (Appendix C)7 will be 
used to assess delirium. 
Knowing the proportion 
of study subjects with 
new-onset delirium will 
assist in designing 
future investigations of 
patients at risk of 
delirium.
3. Background 
Attention is the most crucial cognitive domain required to effectively complete mentally 
challenging tasks by healthy individuals. Many healthy people cannot achieve high executive 
brain functioning tasks due to a lack of focus or attention, leading to poor performance both at 
work and at home. Generally, mild attention deficit is not identified, and daily life stresses are 
usually blamed. Computerized cognitive training programs have shown improved attention 
deficit disorder and mild cognitive impairment. 1 VR is an emerging technology that can improve 
brain functions, including attention. 2 VR engages multiple learning systems, making it a more 
effective natural environment for cognitive training. Accuracy in VR games refers to the user’s 
ability to interact with VE accurately, hit targets, and perform tasks. Attention in VR games refers 
to the user’s cognitive focus and engagement in VE. VR provides an immersive experience that 
can capture a user’s attention more effectively than traditional gaming. There is a strong 
connection between accuracy and attention. When users are more attentive to the game in VE 
and their tasks, it is likely to improve. The immersive nature of VR encourages the user to be 
more focused and engaged, enhancing performance in terms of accuracy. 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 5 of 21
HMRI Basic Protocol Template v23Mar2023
Our group designed and tested a 3D simulated 
software platform prototype called ReCognition 
VR with incorporated exercises in the form of 
games that can improve attention and executive 
functions. ReCognitionVR- software (Figure 1) 
allows users to immerse themselves in a relaxing 
VE; reorient the user to person, time, and 
location; and play mini-games to encourage 
attention, focus, and movement of limbs; and 
record user progress and scores in mini-games.
Critical gaps exist in our knowledge of cognitive 
interventions and their application through VR. 
Data on interventions focused on early cognitive exercise using Virtual Reality Simulation, 
specifically using Oculus Quest 2 and Unity software, are limited. Moreover, many critical 
barriers to implementing cognitive training in clinical protocols exist. Cognitive stimulation 
through VR is a new and upcoming area in technology that is rapidly expanding but is currently 
limited in literature. A lack of understanding or appreciation for the evidence supporting 
cognitive stimulation through VR, specifically gamification, contributes to the barriers. The rapid 
increase and use of VR in other areas urges our team to seek this area for development. 
Major goals: This proposal aims to assess the safety/tolerability, feasibility, and acceptability of 
VR-based cognitive interventions in older surgical patients using ReCognition VR software while 
providing easy delivery of cognitive stimulation exercises provided by VR. 
Preliminary Study:5 Our group conducted a prospective, single center, randomized, controlled 
clinical trial in healthy volunteers from August 2021 to December 2022. Healthy volunteers were 
enrolled based on the American Society of Anesthesiologists (ASA) physical status classification 
system: ASA 1 included those aged >18 to 35 years, and ASA 2 included those aged >60 years. 
The study results (Appendix 1: Final Study Report) were as follows: Feasibility: All study 
participants in both ASA 1 and 2 groups completed the ReCognitionVR-based exercise with 
feasibility of 100%; Acceptability/Usability: The mean SUS scores for ASA 1 and ASA 2 were 
88.17±12.83 and 88.67±9.90, respectively There were no statistically significant differences in 
SUS scores between ASA 1 and ASA 2 (p=0.81); Tolerability: Only four adverse events occurred 
during the study: 3 (20%) in the ASA1 group and 1 (6.67%) in the ASA2 group. Although 1/15 
(6.67%) ASA 1 participants experienced transient dizziness and 1/15 (6.67%) ASA 2 participants 
had a vague undefined mind/brain fog, both participants completed the study interventions. One 
study participant, 1/15 (6.67%) from the ASA 1 group, experienced a transient increase in SBP 
>20% from baseline. No participant experienced more than one adverse event. No serious 
adverse events occurred. The procedure was not interrupted related to an adverse event.
Figure 1: Describes the system architecture to the observer 
and healthy participants.
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 6 of 21
HMRI Basic Protocol Template v23Mar2023
4. Study Design
The study is a single-center, prospective assessment of the feasibility, acceptability, and usability 
of ReCognition VR -based simulated cognitive stimulation to improve attention and focus in 
surgical patients. 
Sample size: We will enroll 30 participants: 15 participants who are ≥60 years of age with 
traditional orientation methods and 15 participants who are ≥60 years of age and receive 
ReCognitionVR-based cognitive exercises.
Justification of sample size: The study is a feasibility study expecting that 70% of participants in 
the study intervention group will complete 20 minutes of the ReCognitionVR-based exercise, 
where each group will be evaluated separately. Descriptive statistics will be used to summarize 
the findings; 15 participants in each group will be recruited. The intent is that this study will 
provide information for a larger, subsequent clinical trial of patients ≥60 years old at risk for 
delirium.
Data and measures to be taken:
The endpoints for this feasibility study are:
Primary Objective:
Safety/Tolerability: We will examine measures that can inform on the safety of the experience to 
be used in the subsequent clinical trial. The measures are:
1. Mean change from pre to 10 minutes of the ReCognition VR-based exercise in:
a. SpO2
b. RR
c.
Blood pressure (Mean BP, Systolic BP, and Diastolic BP)
2. Mean change from pre to end of the ReCognition VR-based exercise in:
a. SpO2
b. RR
c.
Blood pressure (Mean BP, Systolic BP, and Diastolic BP)
Secondary Objectives:
Feasibility: 70% of participants in each group will complete 20 minutes of use of the ReCognition 
VR-based software (a binary outcome).
Acceptability: We will measure the acceptability and usability of the experience based on the 
proportion of participants with a SUS score >35.
VR-games Accuracy: We will report on the proportion of participants who complete the game 
without any user errors and the number of attempts each participant uses to complete the 
game.
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 7 of 21
HMRI Basic Protocol Template v23Mar2023
Exploratory Objective: 
Delirium: We will assess delirium using CAM tool6 or the 4 A’s test7.  Delirium is defined as any 
positive CAM Score or/and score of 4 or above on the 4 A’s test for 72 hours after study 
interventions. 
Accessing data from medical records:
Medical records of the potential study subjects will be reviewed for medical history for the 
inclusion and exclusion criteria described below in section 10. 
Data analysis plan:
We will report the demographic variables of age, sex, race, and ethnicity for each group and the 
clinical characteristics and will review the patient’s medical records for body mass index, history 
of hypertension with active management, drinking status, smoking status, ASA status, pre-
existing medical co-morbidities. If not found in the medical record, we will obtain this 
information. 
The results of this study will be reported using descriptive statistics. Continuous variables will be 
reported as means with standard deviation or medians and interquartile range contingent on the 
normality of the distribution. Categorical variables will be reported using Chi-square or Fisher's 
exact test, as appropriate.
5. Study Intervention 
1. Older patients (≥ 60 years old) scheduled to undergo abdominal surgeries (open or 
laparoscopic or robotic assisted), small bowel and large bowel surgery; cholecystectomy; 
Whipple procedure; pancreatectomy; splenectomy at HMH will be invited to participate. 
2. We will screen patients for inclusion and exclusion criteria and will assign a screening 
number.
3. After signing informed consent, participants will be enrolled in the study and randomized 
using computer-generated randomization software to traditional orientation method 
(control) or ReCognitionVR-based cognitive exercises (experimental). 
4. The experimental group will watch a video on using VR technology, placement of a VR 
headset, and assessment of baseline cognitive function using the Mini-Cog screening 
tool. 
5. All participants will have a frailty screening assessment.9
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 8 of 21
HMRI Basic Protocol Template v23Mar2023
6. The Mini-Cog screening tool will assess the patient's cognitive status of all participants. 
(Appendix D)8
7. The experimental group will receive a 3D- ReCognitionVR-based simulated cognitive 
exercise program targeting attention, organizing thinking, and motor activities using VR 
games. The participant will receive study intervention after arrival to the room from the 
operating room, free of residual anesthesia, by measuring the Richmond Sedation Scale
(RASS)- Appendix – E 10 score of 0. 
8. The detail of the software as follows: 
3-D Recognition Virtual Reality-Based Simulation Sessions Program:
Software Platform: 
The VR platform will consist of 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 9 of 21
HMRI Basic Protocol Template v23Mar2023
-
The VR headsets manufactured by the Oculus Quest 2 glasses (Facebook Inc., USA) 
with stereoscopic vision and stereo sound will be used to show the virtual world to 
participants.
-
Motion Sensor  
-
Flat Screen TV with Software 
The VR headsets manufactured by the Oculus Quest 2 glasses (Facebook Inc., USA) with 
stereoscopic vision and stereo sound will be used to show the VR to study participants. 
After headset placement, the study participants will be able to follow instructions 
provided by virtual nurse AVATAR. The participants will receive low cognitive load 
exercises based on virtual reality techniques, including a relaxed environment, music 
therapy, time orientation, delivery instructions, and task completion motivation. The 
exercise task will focus on attention, organized thinking, and motor activities.
9. If you are in the traditional orientation method, you will be visited by a nurse at the start 
of each nursing shift. The nurse will ask you questions to check your memory and 
attention. Examples of questions include asking you for your name, the date, where you 
are, and what just happened to you. This will be repeated during every nurse shift change 
and is the usual care you would receive, even if you were not in the study.  In this 
method, your vital signs (oxygen levels, how fast you are breathing, and your blood 
pressure) will be measured at different time points after your abdominal surgery as part 
of your standard care. When you wake up from surgery, you will have the traditional 
orientation questions asked of you until you are discharged from the hospital. Your 
participation in this study will be over after you leave the hospital. 
Schedule of Activities
Procedures
Screening*
Day 1, 
Time 1: 
pre
Day 1, 
Time 2: 
10 
minutes
Day 1, 
Time 
3: post
Day 1, 
Time 
4: end 
of 
study
Post 24 
hours
Post 48 
hours
Post 72 
hours
Visit number
Visit 0 or 1
Visit 1
Visit 2
Visit 3
Visit 4
Informed 
consent
X
Demographics
X
Medical history
X
Randomization
X
Administer 
study 
intervention
|--------------------X---------------------|
Concomitant 
medication 
review
X
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 10 of 21
HMRI Basic Protocol Template v23Mar2023
Procedures
Screening*
Day 1, 
Time 1: 
pre
Day 1, 
Time 2: 
10 
minutes
Day 1, 
Time 
3: post
Day 1, 
Time 
4: end 
of 
study
Post 24 
hours
Post 48 
hours
Post 72 
hours
Visit number
Visit 0 or 1
Visit 1
Visit 2
Visit 3
Visit 4
Physical exam 
(including 
height and 
weight)
X
Frailty screening 
assessment
X
Mini-Cog 
screening 
assessment 
X
RASS Score 
X
Pulse oximetry
X
X
X
Respiratory rate
X
X
X
Blood pressure
X
X
X
System User 
Survey
X
Number of 
software and 
device re-starts, 
re-sets. 
X
X
Number of User 
errors 
X
X
X
Number of 
game attempts 
X
X
X
Adverse event 
review and 
evaluation 
X
X
X
X
X
X
X
Pain scores 
(Numeric Pain 
Scale)
X
X
X
X
X
X
X
X
Positive CAM 
or/and 4 A’s 
Test 
X
X
X
X
X
Complete Case 
Report Forms 
(CRFs)
X
X
X
*Screening Visit and Day 1 may occur on the same day
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 11 of 21
HMRI Basic Protocol Template v23Mar2023
Dosing:
The study participants will receive approximately 20 minutes of VR- based cognitive stimulation 
sessions and complete a post-user survey System Usability Scale. 
Acceptability Survey:
Principal Investigator (PI) or a research team member will use the SUS survey to interview the 
study participants.  (Appendix - F)
6. Drugs, Biologics, Devices 
Specifically, VR will be simulated using UNITY software and Oculus Quest (two headsets) for this 
project. The use of ReCognitionVR software is investigational in this proposal. However, in Phase 
1a study we evaluated the feasibility, safety, and acceptability of ReCognitionVR software in 
healthy elderly subjects. The result of the study is uploaded as a clinical study report in MORTI. 
Moreover, the use of VR software has been approved by FDA. There are multiple VR softwares 
that are approved by the FDA. Please see the link below for reference:
Augmented Reality and Virtual Reality in Medical Devices | FDA
7. Collaborative / Multi-site Research
N/A
8. Data Privacy / Confidentiality 
Houston Methodist policies for Protected Health Information (PHI) will be followed, including all 
physical and electronic data security requirements, encrypted devices, and HM password-
protected servers.
All data obtained for the study will be stored in a password-protected spreadsheet on a 
Methodist server and will only be accessible to IRB-approved investigators and research staff at 
Houston Methodist. Data will be completely de-identified at the time of collection and sent to 
the statistician via secure mail for analysis. Research materials will be stored in a password-
protected computer system database on a secure server on the Houston Methodist network. 
Data collected will be transferred and stored on REDCap®, a secure web application for building 
and managing databases. Study personnel requiring access will have their Login/Password 
assigned to the project. Access to clinical study information will be based on individuals' roles 
and responsibilities. All study data will be transmitted over an encrypted SSL (Secure Sockets 
Layer) connection that requires user authentication. This application is designed to be in full 
compliance with the International Conference on Harmonization and Good Clinical Practices 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 12 of 21
HMRI Basic Protocol Template v23Mar2023
(ICH-GCP), the FDA's Code of Federal Regulations (CFR) 21 Part 11 Electronic Record and 
Electronic Signatures, the FDA's "Guidance: Computerized Systems Used in Clinical Trials," and 
the Privacy Rule of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).
Houston Methodist Research Institute (HMRI) policy on record retention will be followed, and 
human subject research data will be kept for a minimum of 6 years after completing the study. 
Research written materials will be stored in the Department of Surgery Research Office (Skurlock 
1150) and electronic materials on password-protected computer systems on a secure server on 
the Houston Methodist network.  
A unique identification code will be assigned to each participant in this study, and the study team 
will maintain the linking log with the study files. The only individuals who can see un-coded 
personal health information include the Study Team and the Institutional Review Board at the 
hospital, employees of the sponsor who check that this study is being done correctly, and 
regulatory authorities where required by law.  
Data to be collected include:

Sex

Age

Race, ethnicity

Height, weight

SpO2 (Time Frame: before, during, and after use of ReCognitionVR software; see 
Schedule of Activities)

Respiratory rate (Time Frame: before, during, and after use of ReCognitionVR 
software; see Schedule of Activities)

Pain scores (using numeric pain rating scale tool)

Safety adverse events
Identifier (or parts of) 
Recorded Disclosed 
Comment
All elements of dates (except year) for dates 
directly related to an individual, including 
patient names, birth date, admission date, 
discharge date, and date of death; and all 
ages over 89 and elements of dates 
(including year) indicative of such age
Yes
No
Necessary for complete data 
analysis
Phone numbers; Fax numbers
Yes
No
Necessary to complete a 
questionnaire
Medical record numbers
Yes
No
Necessary to organize data 
collection
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 13 of 21
HMRI Basic Protocol Template v23Mar2023
Identifier (or parts of) 
Recorded Disclosed 
Comment
Any other unique identifying number, 
characteristic, or code
Yes
No
Virtual cognitive 
interventions are frequently 
delivered 
9. Data and Specimen Banking 
No specimens will be obtained, stored, or banked in this study.  
10.
Study Population 
This study will be a single-center study of older patients who underwent abdominal surgeries 
and will be conducted at Houston Methodist Hospital. We will enroll 30 patients scheduled to 
undergo abdominal surgery who are ≥60 years of age. The rationale for enrolling older patients is 
that older surgical patients are at high risk for the development of delirium. 
A total of 30 patients will be prospectively enrolled. 15 patients will receive the standard of care 
/ re-orientation technique, and 15 patients will receive ReCognitionVR-based cognitive exercises. 
All participants will be given post-use surveys to assess usability and acceptability outcomes.
Inclusion Criteria:
1. Patients ≥ 60 are scheduled to undergo the following abdominal surgeries (open or 
laparoscopic or robotic assisted) small bowel and large bowel surgery; cholecystectomy; 
Whipple procedure; pancreatectomy; splenectomy. 
2. RASS Score 0
Exclusion Criteria: 
1. Subjects with baseline cognitive impairment.
2. Person with active psychiatric disorders and being treated with medications, especially 
schizophrenia.
3. Person who is deaf or blind.
4. Person with an underlying cognitive disorder or associated phobias (e.g., claustrophobia).
5. Person participating in other clinical trials involving drugs, biologics, devices, or 
behavioral interventions.
6. Active seizure disorders.
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 14 of 21
HMRI Basic Protocol Template v23Mar2023
11.
Screening and Recruitment
All participants will be screened by the PI and clinical research staff, who have been trained in 
the clinical investigational plan, to determine if the potential participant is eligible for 
enrollment. The screening for potential participants will be from within the PI’s department. 
Potential participants will be assigned a screening number which is recorded in an Excel sheet; all 
participants who receive the study intervention will be noted. All participants must meet 
eligibility criteria (and if not, which eligibility criteria were not met will be recorded); reasons for 
not meeting enrollment criteria or receiving study intervention will be recorded. No participants 
belonging to a vulnerable population will be enrolled. 
During the informed consent process, the investigator or designee, who has been trained on the 
protocol, will explain the nature and scope of the intervention, potential risks, and benefits of 
participation and answer questions from the potential participants. All participants will sign and 
date the Institutional Review Board (IRB)/Ethics Committee (EC) approved informed consent 
form before any study-specific procedures are performed. In addition, the signed informed 
consent will be retained with the research records, and a copy will be given to the participant.
Medical records will be reviewed for screening.
12.
Withdrawal of Subjects
A participant may discontinue his or her participation without giving a reason at any time during 
the study. For example, the PI may withdraw a participant due to failure to comply with study 
intervention requirements, or the participant is uncooperative or refuses to continue in the 
study intervention.  The data from these participants will be retained in the study file and 
analyzed.
Participants will be withdrawn from the study if they do not receive any study interventions. At 
the moment of withdrawal, all data related to the participant will be removed from the 
corresponding Excel documents and waivers will be shredded.  
13.
Provisions to Protect the Privacy Interests of Subjects 
Only the minimum amount of personal information needed to conduct this study will be 
collected regarding participants' privacy interests. Study participants will be informed that the 
only individuals who can see un-coded personal health information include the following: the 
Study Doctor, other employees who work on this study (including the Institutional Review Board) 
at the hospital, employees of the sponsor who check that this study is being done correctly, and 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 15 of 21
HMRI Basic Protocol Template v23Mar2023
regulatory authorities where required by law. In addition, participants will be carefully informed 
about the Release of Health Information section in the Informed Consent Form (ICF), which 
describes who will access their information and how it will be used. We will emphasize that 
participation in this study is voluntary and that participants can choose at any time to cease 
participation and revoke authorization to use and disclose their information.
14.
Risks to Subjects
The risks below are associated with the use of the Oculus Quest 2 VR Headset Device. 
All adverse events (AEs) will be captured and recorded at each time point. We will report AEs as 
a proportion of study participants who developed AEs.
Specific AEs to be monitored will include:
Neurological AEs: (Cybersickness is defined as new-onset blurry vision, double vision, 
dizziness, headaches, eye fatigue, drowsiness, disorientation, and apathy) within 5 minutes 
after starting the study intervention). 
Cardiac Adverse Events:  New-onset hypotension (SBP <90 mmHg and DBP <60 mmHg), 
Bradycardia (HR < 50), Tachycardia (HR> 100), and Arrhythmias (Supraventricular or 
ventricular ) with HR> 150 beats per minutes within 5 minutes after the starting of 3D 
Simulated VR sessions. Or changes >20% from baselines.
Pulmonary Adverse Events: New-onset hypoxia: SpO2 < 88%, Respirator rate > 35 
breaths/minute within 5 minutes after starting 3D Simulated VR sessions.  
       The safety precautions to minimize the risk to participants are as follows:

Vital signs BP, HR, RR, SPO2, and pain scores (using numeric pain rating scale tool) will 
be monitored before, during, and after using ReCognitionVR software.

Mitigation strategy: The gaming environment underwent careful consideration to 
alleviate cybersickness. We have limited neck motion in the games to avoid sensory 
conflict, as the subject will remain seated or in a bed during use. Both controllers can 
still move freely, and the game's design was such that the game could be played from 
a seated position. In addition, study observers can quickly intervene if a subject 
begins to feel cybersickness symptoms. The study subjects will be recommended to 
close eyes and take off the headset until the symptoms subside. 
Other Risks
You may be at risk for loss of confidentiality, meaning your information could become known to 
someone not involved in this study. If this happens, it could result in damage to your 
reputation, which could also affect your relationships with family and friends, affect your 
employment, or make it harder to get insurance or a job.
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 16 of 21
HMRI Basic Protocol Template v23Mar2023
15.
Potential Benefits 
Direct benefit to participants is not anticipated. The data from this study is expected to inform a 
subsequent clinical trial of using the ReCognition VR-based software in patients at risk for 
delirium.
16.
Financial and Economic Issues 
The participants in this study will not be compensated, and there is no additional cost to 
participants for taking part in this study.
17.
Data Safety Plan 

The research team plans to periodically evaluate data collected regarding the benefits 
and harms of the study to evaluate the participants' safety.

Data reviewed periodically will be the following:
o
Adverse effects occurred during the study intervention (dizziness, double vision, 
disorientation, etc.)
o
Adverse effects during and after the study intervention
o
Delirium on days 1, 2 and 3

Safety information will be collected during study visits.

Data collection will occur during the game. Specifically, after the user plays the minigame 
in the ReCognitionVR Software. Safety data collection will begin before the study 
intervention and also be collected during and after the study intervention. 
All study data will be transmitted over an encrypted SSL connection that requires user 
authentication. This application is designed to be in full compliance with the International 
Conference on Harmonization and Good Clinical Practices (ICH-GCP), the FDA's Code of Federal 
Regulations (CFR) 21 Part 11 Electronic Record and Electronic Signatures, the FDA's "Guidance: 
Computerized Systems Used in Clinical Trials," and the Privacy Rule of the HIPAA.
HMRI policy on record retention will be followed, and human subject research data will be kept 
for a minimum of 6 years after the completion of the study. Research materials will be stored in \ 
on password-protected computer systems on a secure server on the Houston Methodist 
network.  
The roles and responsibilities of the Investigators are (a) assuring that the trial is conducted 
according to the Protocol and Manual of Procedures (MOP); (b) identifying, recruiting, and 
enrolling participants; (c) obtaining informed consent from each participant and protecting their 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 17 of 21
HMRI Basic Protocol Template v23Mar2023
rights; (d) collecting and entering study data into REDCap, and following participants through 
study completion: (e) assuring regular IRB/REB review.
18.
Informed Consent Documentation and Process 
The informed consent will be obtained in written format using a consent document that is HMRI-
approved. The investigators involved in the consent process will all be credentialed at HMRI to 
participate in research at HMH. System Policy and Procedure RE-12 will be followed. The PI and 
investigators will identify the surgical patient from the surgeon’s clinic, pre-anesthesia clinic, and 
operating room procedures and surgery list.  Potential participants may also consent on the 
same day of use of ReCognitionVR software. During the informed consent process, the 
investigator or designee, who has been trained on the protocol, will explain the nature and 
scope of the intervention, potential risks, and benefits of participation and answer questions 
from the potential participants. All participants must sign and date the Institutional Review 
Board (IRB) approved informed consent form.
Additionally, the signed informed consent must be kept in the participant's medical records, and 
a copy must be given to the participant. During the informed consent process, the investigator 
and designee, who have been trained on the protocol, will explain the nature and scope of the 
intervention, potential risks, and benefits of participation and answer questions from the 
potential participants. Participants will be informed that the study is investigational and that 
their participation in the study is voluntary. They will be informed that they may refuse to 
participate or may withdraw consent to participate at any time, and for any reason, without 
jeopardizing their future care at this institution.
The PI and study team will ensure enough time to explain the ICF to the participants and answer 
all questions before signing the ICF. The study and the contents of the ICF will be explained in 
detail, and ample time will be given to the study participant to read the consent and discuss it. 
Questions will be encouraged and will be answered by the participants before the document is 
signed. The study team will not proceed if adequate time is not available for the participant to 
demonstrate an understanding of the study and indicate a desire to participate.
19.
Waiver of Informed Consent and /or Authorization
No waiver of informed consent or authorization is requested. Medical records will be reviewed. 
The study team will require a screening waiver to review the potential patient’s medical record 
for inclusion and exclusion criteria. No PHI will be recorded or stored if the participant does not 
fit the study eligibility or inclusion criteria. The study team will only collect the minimum 
necessary information to verify eligibility per inclusion or exclusion criteria. If the participant is 
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 18 of 21
HMRI Basic Protocol Template v23Mar2023
eligible based on the study's inclusion criteria and agrees to participate in the study, then the PI 
or study team will gain informed consent before collecting any PHI or conducting any study-
related procedures. 
Waiver of HIPAA Authorization for 
Research
Complete this section if you will access identifiable health information in a 
patient’s electronic health record or other record held by Houston Methodist 
Hospital and you are not obtaining a signed authorization from the patient.  
This waiver can apply to health information accessed to identify potential 
research participants or for research involving retrospective chart reviews.  
1. Purpose of the Waiver: 
   ☐   Chart review study
   ☐   Partial waiver of authorization to identify, prescreen and contact 
potential participants.  
   ☐   Alteration of the requirements for a HIPAA Authorization to remove 
the signature. *  
   ☐  Other Please explain
* Note if the IRB waives the signature requirement, the participant must 
receive a copy of the HIPAA authorization language.  
2.  Provide protocol-specific responses to the following items that describe 
why the waiver is being requested for the use of PHI in this research.
a. The IRB must find that the use/disclosure of protected health information 
(PHI) involves no more than minimal risk to the privacy of individuals.  
Please select the safeguards your team will use to meet this requirement. 
 ☐   Electronic safeguards, such as password protection, data 
encryption, and institution firewall, will be used to protect PHI
 ☐   Physical safeguards, such as locked cabinets, locked filing room, 
secure, locked office area, will be used to protect PHI
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 19 of 21
HMRI Basic Protocol Template v23Mar2023
  ☐  The study team will record only anonymous data or coded data that 
are linked to the participants’ identity through a file that is separate 
from the data.    
  ☐   Administrative safeguards such as policies and procedures, staff 
education on the HIPAA Privacy Rule. 
  ☐  Other:      
c. Describe why the research cannot practicably be conducted without the 
waiver or alteration of patient authorization to use PHI in research
☐  Access to and use of PHI is necessary to obtain information of 
potential subjects. 
☐  The number of screen failures is anticipated to be high for this 
research and access to the PHI to confirm potential study eligibility 
will prevent unnecessary contact with potential participants. 
         ☐  Too many participants will be lost to follow up or will not answer the 
request for an authorization to conduct the record review study.  
☐  Other:      
 
d.  Describe why the research cannot practicably be conducted without access 
to and use of
    the PHI:
    ☐  The study team will access the minimum PHI necessary to contact 
potential participants to assess their interest and eligibility. 
   ☐  The study team will access the minimum PHI necessary to prescreen 
for eligibility and to contact potential participants to assess their 
interest. 
    ☐  The study team will access the minimal PHI necessary data elements 
to answer the research question.
       
3. Identify 
List the identifiers you will record. 
   ☐   Name
   ☐   Address (all geographic subdivisions smaller than state, including street 
address, city county, and zip code)
   ☐   All elements (except years) of dates related to an individual (including 
birthdate, admission date, discharge date, date of death, and exact age if 
over 89)
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 20 of 21
HMRI Basic Protocol Template v23Mar2023
   ☐   Telephone number 
   ☐   Fax number
   ☐   Email addresses 
   ☐   Social Security Number
   ☐   Medical record number
   ☐   Health plan beneficiary number
   ☐   Account number
   ☐   Certificate or license number
   ☐   Vehicle identifiers and serial numbers, including license plate numbers
   ☐   Device identifiers and serial numbers
   ☐   Web URL
   ☐   Internet Protocol (IP) Address
   ☐   Finger or voice print
   ☐   Photographic image - Photographic images are not limited to images of the 
face.
   ☐   Any other characteristic that could uniquely identify the individual
By submitting this request for waiver of patient authorization, I certify:
(1)
That the identifiers will be destroyed at the earliest opportunity consistent 
with the conduct of the research as defined by federal, state, and/or local 
laws and regulations.  
(2)      The PHI will not be reused or disclosed to any other person or entity, except 
as required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of PHI would be permitted.
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024

Feasibility and acceptability of ReCognitionVR-based cognitive stimulation in surgical patients.
Page 21 of 21
HMRI Basic Protocol Template v23Mar2023
20.
References
1.
Rizzo, A. A., Buckwalter, J. G., Bowery, T., Van Der Zaag, C., Humphrey, L., Neumann, C., et al. 
(2000). The virtual classroom: a virtual reality environment for the assessment and rehabilitation 
of attention deficits. Cyber Psychol. Behav. 3, 483–499. doi: 10.1089/10949310050078940doi: 
10.1002/14651858.CD008349.pub4
2.
Lee E, Kim J. Cost-benefit analysis of a delirium prevention strategy in the intensive care unit 
[published online ahead of print, 2014 Oct 29]. Nurs Crit Care. 2014;10.1111/nicc.12124. 
doi:10.1111/nicc.12124.
3.
Turon M, Fernandez-Gonzalo S, Jodar M, et al. Feasibility and safety of virtual-reality-based early 
neurocognitive stimulation in critically ill patients. Ann Intensive Care. 2017;7(1):81. 
doi:10.1186/s13613-017-0303-4.
4.
Gang Li, Joaquin A. Anguera, Samirah V. Javed, Muḥammad Adeel Khan, Guoxing Wang, Adam 
Gazzaley; Enhanced Attention Using Head-mounted Virtual Reality. J COGN NEUROSCI 2020; 32 
(8): 1438–1454. doi: https://doi.org/10.1162/jocn_a_01560
5.
Usability, Acceptability, and Safety of Virtual Reality-based Cognitive Intervention. 
ClinicalTrials.gov Identifier: NCT05583903. Usability, Acceptability, and Safety of Virtual Reality-
based Cognitive Intervention - Full Text View - ClinicalTrials.gov.
6.
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the 
confusion assessment method. A new method for detection of delirium. Ann Intern Med. 
1990;113(12):941-948.
7.
Evensen S, Hylen Ranhoff A, Lydersen S, Saltvedt I. The delirium screening tool 4AT in routine 
clinical practice: prediction of mortality, sensitivity and specificity. Eur Geriatr Med. 2021 
Aug;12(4):793-800.
8.
Borson S, Scanlan JM, Chen PJ et al. The Mini-Cog as a screen for dementia: Validation in a 
population-based sample. J Am Geriatr Soc 2003; 51:1451–1454.
9.
Abellan van Kan G, Rolland YM, Morley JE, Vellas B. Frailty: toward a clinical definition. J Am Med 
Dir Assoc. 2008;9(2):71-72.
10. Ely EW, Truman B, Shintani A, Thomason JWW, Wheeler AP, Gordon S et al. Monitoring sedation 
status over time in ICU patients: the reliability and validity of the Richmond Agitation Sedation 
Scale (RASS). JAMA 2003; 289:2983-2991.
IRB ID:  PRO00037724  IRB Approved: 10/10/2023 - 10/9/2024