Immersive Virtual Reality Applied to Therapeutic Physical Exercise in Cellular Therapy

Overview

Cell therapy (CT), including hematopoietic stem cell transplantation (HSCT) and advanced CAR T-cell therapies, is used for the treatment of oncohematological and other diseases. HSCT is associated with treatment-related toxicities, including fatigue, muscle weakness, and reduced functional capacity due to intensive conditioning chemotherapy, immunosuppressive treatments, corticosteroids, and complications such as infections or graft-versus-host disease. Emotional symptoms, including anxiety, depression, fear, and frustration, also affect patients' recovery and ability to regain functional independence. Evidence indicates that exercise interventions improve emotional well-being, fatigue, quality of life, physical function, cardiovascular fitness, and muscle mass in patients with hematological malignancies and HSCT recipients. Virtual reality (VR) has emerged as an innovative tool in rehabilitation, supporting patient motivation, exercise guidance, and monitoring. Immersive virtual reality (IVR), through head-mounted displays and multisensory environments, enhances the sense of presence and engagement. Studies suggest that IVR-based exercise programs are feasible, improving functional abilities, quality of life, satisfaction, and adherence. Since 2017, a Therapeutic Exercise program for patients admitted for HSCT has been implemented at Álvaro Cunqueiro Hospital (Vigo) through collaboration between the Physiotherapy Unit and the Hematology Department. Before admission, patients undergo a physical assessment, receive an individualized exercise plan, education, and a therapeutic exercise guide. Based on clinical experience, the team hypothesizes that integrating IVR into therapeutic exercise may improve motivation, adherence, and emotional well-being during hospitalization.

Detailed description

Cell therapy patients, including hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell (CAR-T) therapy recipients, frequently experience significant physical and emotional impairments during hospitalization. Treatment-related factors such as intensive chemotherapy conditioning, immunosuppressive therapies, corticosteroid exposure, infections, and other complications may contribute to fatigue, reduced muscle strength, decreased functional capacity, anxiety, depression, and impaired quality of life.

Therapeutic exercise has demonstrated benefits in patients with hematological malignancies and HSCT recipients, improving physical function, fatigue, emotional symptoms, quality of life, and overall health status. However, maintaining motivation and adherence to exercise programs during prolonged hospital stays remains challenging.

Immersive virtual reality (IVR) has been increasingly investigated as a tool to enhance rehabilitation strategies. Through head-mounted displays and interactive virtual environments, IVR provides an immersive and engaging experience that may improve patient motivation, exercise participation, and emotional well-being. Previous studies have shown that IVR-based exercise interventions are feasible and may promote adherence and satisfaction in different clinical populations.

At Álvaro Cunqueiro Hospital (Vigo, Spain), a Therapeutic Exercise Program for patients undergoing hematopoietic stem cell transplantation has been implemented since 2017 through collaboration between the Physiotherapy Unit and the Hematology Department. This program includes pre-admission physical assessment, individualized exercise prescription, patient education, and monitoring during hospitalization.

This clinical trial aims to evaluate whether the addition of an immersive virtual reality intervention to a therapeutic exercise program improves adherence, feasibility, physical performance, emotional status, quality of life, and patient experience during hospitalization in patients receiving cellular therapy.

Interventions

• Device Intervention with IVR
  The RVI intervention program will consist of the following phases: * Phase 1: Exposure to introductory scenarios and use of the RVI software and hardware, adaptation to virtual environments, observation of passive scenarios aimed at emotional balance, and interactive scenarios involving general mobility and neuromuscular activation. Week 1. * Phase 2: Progression towards tasks that improve response times and attentional mechanisms. Starting in week 2. * Phase 3: More complex multicomponent phys
• Other Control
  Intervention based on the standard treatment program of activities of routine clinical practice: Breathing exercises, resistance exercises with and without weights and aerobic exercises.

Primary outcome measures

• Timed Up and Go (TUG) Test Time [Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)]
• Five Times Sit-to-Stand (5xSTS) Test Time [Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)]
• Handgrip Strength [Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)]
• Two-Minute Step Test (2MST) Step Count [Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)]
• Number of Scheduled Exercise Sessions [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]
• Number of Clinically Feasible Exercise Sessions [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]
• Number of Completed Exercise Sessions [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]
• Percentage of Completed Clinically Feasible Exercise Sessions [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]
• Exercise Session Duration [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]
• Exercise Adherence [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]

Secondary outcome measures (12)

• Sex [Time frame: Baseline (Day of admission)]
• Age [Time frame: Baseline (Day of admission)]
• Type of Hematopoietic Therapy [Time frame: Baseline (Day of admission)]
• Hematological Diagnosis [Time frame: Baseline (Day of admission)]
• Body Mass Index (BMI) [Time frame: Baseline (Day of admission)]
• Anxiety Score (HADS-A) [Time frame: Baseline (Day of admission), hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks) and Follow-up (3 months ± 2 weeks)]
• Depression Score (HADS-D) [Time frame: Baseline (Day of admission), hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks) and Follow-up (3 months ± 2 weeks)]
• Quality of Life (EORTC QLQ-C30) [Time frame: Baseline (Day of admission), hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks) and Follow-up (3 months ± 2 weeks)]
• Quality of Life (FACT-BMT) [Time frame: Baseline (Day of admission), hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks) and Follow-up (3 months ± 2 weeks)]
• Pain Intensity (Visual Analog Scale, VAS) [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]
• Analgesic Treatment Level [Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)]
• Simulator Sickness Questionnaire (SSQ) Score [Time frame: During intervention, Intermediate assessment and hospital discharge (from day 1 to hospital discharge, 28 days±2 weeks)]

Eligibility criteria

Inclusion criteria

• Patients aged 18 years or older.
• Signed informed consent.
• Patients eligible for CT scan at the Alvaro Cunqueiro Hospital.
• Patients capable of performing therapeutic exercise independently, based on an objective initial functional assessment.
• The clinical investigator, in their professional judgment, determines that the patient can adhere to all study requirements.

Exclusion criteria

• Patients under 18 years of age.
• Any medical condition or mental illness that could interfere with understanding HIP and CI.
• Patients participating in another clinical trial.
• Balance disorders that increase the risk of falls.
• Severe visual and/or auditory impairments that prevent participation in the session.
• History of vertigo, seizures, or epileptic fits.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Spain · 1 center

• Hospital Álvaro Cunqueiro (Vigo) — Vigo

Identifiers

NCT: NCT07679958 · RVI-ET

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗