Use of VIrtual REAlity to Reduce Postoperative Anxiety and Pain After Surgery for Colorectal Cancer (VIREA)

Virtual Reality Immersion With 360° Virtual Reality Headset to Reduce Postoperative Anxiety and Pain After Surgery for Colorectal Cancer: a Randomized Controlled Pilot Trial - VIREA Trial

In patients operated for colorectal cancer, pain, anxiety and depression are important factors in postoperative rehabilitation. The use of new technologies, as virtual reality immersion, could further improve their postoperative management. To date, no study has evaluated the potential benefits of using virtual reality before and after colorectal cancer surgery. The main objective is to determine if virtual reality can reduce postoperative anxiety in patients undergoing colorectal cancer surgery.

To answer this question, the investigators plan to execute a randomized controlled, single-center, open-label, superiority interventional trial. Patients will be randomized into 2 parallel arms: 1 interventional "virtual immersion" arm and 1 "control" arm.

Patients with colorectal cancer, regardless of oncological stage, or a colorectal lesion deemed endoscopically unresectable, with an indication for elective surgical management by laparotomy or laparoscopy will be included.

For patients in the interventional arm, virtual reality headset is put on the day before the operation and in the morning just before going down to the operating theatre. Colorectal cancer surgery then proceeds as usual. In the postoperative period, virtual reality sessions are offered every day and on request without any limit in number. Virtual reality immersion offers a visual and auditory experience during a soothing journey through visual worlds filmed in natural environments. This is a purely contemplative mode, lasting maximum 30 minutes.

For the control arm, patients are treated according to the usual practices of the department and do not have access to virtual reality.

The main purpose is to show a greater decrease in anxiety in the interventional group by measuring the absolute difference between the State-Trait Anxiety Inventory scores before surgery and at discharge.

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Colon Tumor, Malignant; Rectum Tumor
• Intervention / Treatment: Behavioral: Pre-operative use of virtual reality headset; Procedure: Standard surgery; Behavioral: Post-operative use of virtual reality headset

Detailed Description

The investigators plan to execute a randomized controlled, single-center, open-label, superiority interventional trial. Patients will be randomized into 2 parallel arms: 1 interventional "virtual immersion" arm and 1 "control" arm.

Randomization (1:1) will be stratified by cancer type (colon vs rectum). The randomization list will be balanced by small blocks of different sizes, randomly alternated to make it unpredictable. The block sizes will be provided in the final study report. The randomization list will be created by a member of the Digestive and Oncological Surgery department not involved in the study and will be added in REDCap software.

Study process:

- Preoperative consultation: information, surgery planning, obtaining patient consent, randomization and provision of 2 self-administered questionnaires: State-Trait Anxiety Inventory (STAI A "state" anxiety - French version) and CES-D (Center for Epidemiologic Studies - Depression - French version) to be completed at home.

Note: measures of depression (CES-D, Center for Epidemiologic Studies - Depression - French version) and alcohol and tobacco consumption are included. These are indeed confounding factors of anxiety and potential moderating factors of virtual reality's effectiveness.

• Beginning of the study (7 days before surgery): all patients filled in the self-questionnaires at home and brought them the day of the surgery.
• For the interventional arm, patients receive care according to the usual practices of the department as well as virtual reality. Virtual reality immersion offers a visual and auditory experience during a soothing journey through visual worlds filmed in natural environments. Virtual reality headset is put on the day before the operation and in the morning just before going to the operating theatre (only on the morning of the operation for patients hospitalized the same day). The colorectal cancer surgery then proceeds as usual. In the postoperative period, virtual reality sessions are offered every day and on request without any limit in number (day and night). Virtual reality sessions take place in the patient's room in bed or in the armchair on a fixed point, with a maximum duration of 30 minutes. The patient can stop the session at any time. The masks are cleaned before and after each use (Anios® wipes) and brought to the patient by the medical or paramedical staff (nurses only). Virtual reality sessions are prescribed by the medical staff using the software used in the department (Dxcare®). For each session, nurses record the duration of the session, the level of anxiety before the session (numerical scale with a score between 0 and 10), the reasons for a potential refusal, the tolerance and any comments on the programs used.
• For the control arm: patients are treated according to usual practices of the department and do not have access to virtual reality.
• End of study: at the end of the hospitalization, the patients fill in the same self-questionnaire State-Trait Anxiety Inventory (STAI A anxiety "state" - French version). In case of prolonged hospitalization for any reason, the end date of study, with the completion of the questionnaire, is set to the 30th postoperative day.
• No specific post-interventional follow-up is required for this research. The patients included in this study will continue their usual follow-up according to their initial condition and the department's procedures.

The main purpose is to show a greater decrease in anxiety in the interventional group by measuring the absolute difference between the State-Trait Anxiety Inventory scores before surgery and at discharge.

Sample size calculation:

• Control group: decrease of 2.55 points (STAI after-STAI before).
• Intervention group: decrease of 3.1875 points (STAI after-STAI before).
• With a relative difference of 25% (i.e. a difference of 0.6375 +/- 1.2) between the two groups, for an alpha risk of 5% and a power of 80%, 57 patients per arm are required, i.e. a total of 114 patients. To overcome the missing data risk, a 10% addition of patients was estimated, i.e. 124 patients in total.

The main analysis will be an intention-to-treat and per-protocol method. The primary endpoint will be compared between groups by linear regression adjusted for stratification factor and the STAI score at D-7. The application conditions will be checked by studying the residuals. No interim analysis is planned.

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yannick VACHER; Phone Number: 33 1 44 84 17 30; Email: gestion-locale.drc@aphp.fr
• Study Contact Backup: Name: Natacha Nohilé

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • Hôpital européen Georges-Pompidou AP-HP
    • Contact: Gilles MANCEAU, MD, PhD
    • Contact: Antoine Cazelles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with colorectal cancer (colon or rectum), regardless of oncological stage and neo-adjuvant treatments received, or a colorectal lesion judged as endoscopically unresectable, with indication for surgical management either by laparotomy or laparoscopy
• Elective surgery
• Patient ≥ 18 years old
• Patient affiliated to a social security system or entitled to it
• Patient who has received full information on the research organization and has given written consent

Exclusion Criteria:

• Complicated tumour (perforation, occlusion) requiring emergency surgery
• Non-French speaking patient
• Patient subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
• Pregnant or breastfeeding woman
• Patient benefiting from the AME
• Epilepsy
• Severe visual or hearing impairment that does not allow the use of headphones
• Autism spectrum disorder
• Claustrophobia
• Confusion
• Medical history of schizophrenia, schizotypal disorders and delusional disorders, and/or patients requiring treatment with : Neuroleptics (Abilify = Aripiprazole and Abilify Now, Clopixol = Zuclopenthixol, Haldol = Haloperidol and Haldol Decanoas, Largactil = Chlorpromazine, Leponex = Clozapine, Loxapac = Loxapine, Nozinan = Levomepromazine, Risperdal = Risperidone and Xeplion and Trevicta, Solian = Amisulpride, Tercian = Cyamemazine, Tiapridal = Tiapride, Xeroquel = Quetiapine, Zyprexa = Olanzapine and Zypadhera); Thymoregulators (Depakote / Depamide = Valproate de Sodium, Lamictal = Lamotrigine, Tegretol = Carbamazepine, Teralithe = Lithium)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immersive reality group; patients receive care according to the usual practices of the department as well as virtual reality. Virtual reality immersion offers a visual and auditory experience during a soothing journey through visual worlds filmed in natural environments. Virtual reality headset is put on the day before the operation and in the morning just before going to the operating theatre (only on the morning of the operation for patients hospitalized the same day). The colorectal cancer surgery then proceeds as usual. In the postoperative period, virtual reality sessions are offered every day and on request without any limit in number (day and night).	Behavioral: Pre-operative use of virtual reality headset; Patient use the virtual reality headset the day before and / or the day of the surgery; Procedure: Standard surgery; Patient are operated as needed for treatment of colorectal cancer (usual care); Behavioral: Post-operative use of virtual reality headset; Patient use the virtual reality headset as many time as they want after the surgery during a maximum of 30 days
Active Comparator: Standard care group; patients are treated according to usual practices of the department and do not have access to virtual reality.	Procedure: Standard surgery; Patient are operated as needed for treatment of colorectal cancer (usual care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety assessment	Change from State-Trait Anxiety Inventory (STAI-A) scores at D-7 before surgery and at discharge (maximum at day 30 after surgery).	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total painkiller use (opioids and non-opioids) during hospitalization	painkillers and their use are prescribed and referenced in the software used in our department (Dxcare®). Data will be collected every day to obtain daily and total consumption.	Up to 30 days
Pain assessment	Maximum pain experienced by the patient during the hospital stay using the numerical pain scale (NPS): nurses record patients' pain at least 4 times a day and note it directly in Dxcare® software (NPS 0 = no pain, NPS 10 = maximal pain) .	Up to 30 days
Total anxiolytic use (benzodiazepines, related hypnotics, hydroxyzine) during hospitalization	Anxiolytics and their use are prescribed and referenced in the software used in our department (Dxcare®). Data will be collected every day to obtain daily and total consumption.	Up to 30 days
Adverse effects of virtual reality immersion	Main adverse effects expected (nausea, vomiting, vertigo, headaches). Virtual reality sessions will be subject to a medical prescription on the software used in our department (Dxcare®). To validate each session, nurses will have to answer a questionnaire stating session duration, anxiety level before the session, reasons for a potential refusal, tolerance, possible comments on the programs used and number of sessions per day.	Up to 30 days
Morbidity and mortality	Severe morbidity (Clavien Dindo classification)	Up to 30 days
Confounding factors of anxiety	Measures of depression (CES-D, Center for Epidemiologic Studies - Depression - French version) and alcohol and tobacco consumption are included. These are indeed confounding factors of anxiety and potential moderating factors of virtual reality's effectiveness.	7 days before surgery
Morbidity	Transit recovery time	Up to 30 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: VR 4 GOOD
• Investigators: Principal Investigator: Gilles MANCEAU, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Eijlers R, Utens EMWJ, Staals LM, de Nijs PFA, Berghmans JM, Wijnen RMH, Hillegers MHJ, Dierckx B, Legerstee JS. Systematic Review and Meta-analysis of Virtual Reality in Pediatrics: Effects on Pain and Anxiety. Anesth Analg. 2019 Nov;129(5):1344-1353. doi: 10.1213/ANE.0000000000004165.
• Mols F, Schoormans D, de Hingh I, Oerlemans S, Husson O. Symptoms of anxiety and depression among colorectal cancer survivors from the population-based, longitudinal PROFILES Registry: Prevalence, predictors, and impact on quality of life. Cancer. 2018 Jun 15;124(12):2621-2628. doi: 10.1002/cncr.31369. Epub 2018 Apr 6.
• Bradt J, Dileo C, Myers-Coffman K, Biondo J. Music interventions for improving psychological and physical outcomes in people with cancer. Cochrane Database Syst Rev. 2021 Oct 12;10(10):CD006911. doi: 10.1002/14651858.CD006911.pub4.
• Parker S, Zipursky J, Ma H, Baumblatt GL, Siegel CA. A Web-based Multimedia Program Before Colonoscopy Increased Knowledge and Decreased Anxiety, Sedation Requirement, and Procedure Time. J Clin Gastroenterol. 2018 Jul;52(6):519-523. doi: 10.1097/MCG.0000000000000958.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: pain; anxiety; colon cancer; virtual reality; malignant colon tumor; malignant rectum tumor; virtual reality immersion
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Postoperative Complications; Pain; Neurologic Manifestations; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Neoplasms; Pain, Postoperative; Rectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: APHP211134; IDRCB 2021-A01436-35 (Registry Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
• IPD Sharing Time Frame: Two years after the last publication

IPD Sharing Access Criteria

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Data sharing must respect the agreements made with funders.

Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement.

Processing of shared data must comply with European General Data Protection Regulation (GDPR).

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No