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NCT Number: NCT07679958

Immersive Virtual Reality Applied to Therapeutic Physical Exercise in Cellular Therapy

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hospital Álvaro Cunqueiro (Vigo)

Vigo, Pontevedra, 36312, Spain

Location contact

Carmen Albo López, MD

CONTACT

[email protected]

986 217 832

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Intervention with IVR

Device

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 physical exercise based on boxing techniques, movements of the upper limbs, trunk, head, and lower limbs, coordination exercises, and cyclical cardiovascular exercise.

Other names: Oculus Quest 3, Meta Platforms

Control

Other

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 outcomes

  1. Timed Up and Go (TUG) Test Time

    Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)

    The time (in seconds) required to stand up from a chair, walk 3 meters, turn around, walk back, and sit down. Lower values indicate better functional mobility.

  2. Five Times Sit-to-Stand (5xSTS) Test Time

    Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)

    The time (in seconds) required for a participant to rise from a standard chair and sit down five consecutive times as quickly as possible without using the upper limbs for assistance. Lower values indicate better lower-extremity muscle strength and functional performance.

  3. Handgrip Strength

    Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)

    andgrip strength is assessed using a handheld dynamometer. Participants perform a maximal voluntary isometric grip contraction according to standardized testing procedures. The highest value recorded is expressed in kilograms (kg). Higher values indicate greater muscle strength.

  4. Two-Minute Step Test (2MST) Step Count

    Time frame: Baseline (Day of admission) and Follow-up (3 months ± 2 weeks)

    Participants march in place for 2 minutes, raising each knee to a predetermined height midway between the patella and iliac crest. The outcome is the total number of times the right knee reaches the target height during the test, expressed as the number of steps. Higher values indicate better aerobic endurance and functional capacity.

  5. Number of Scheduled Exercise Sessions

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    The total number of scheduled exercise sessions completed by each participant during hospitalization. Higher values indicate greater adherence to the exercise intervention.

  6. Number of Clinically Feasible Exercise Sessions

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    The total number of exercise sessions considered feasible according to the participant's clinical condition during hospitalization, recorded as the number of sessions.

  7. Number of Completed Exercise Sessions

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    The total number of clinically feasible exercise sessions that were completed by the participant during hospitalization, recorded as the number of sessions.

  8. Percentage of Completed Clinically Feasible Exercise Sessions

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    The percentage of clinically feasible exercise sessions that were completed during hospitalization, calculated as: (completed feasible sessions / clinically feasible sessions) × 100. Higher values indicate greater compliance with the sessions considered feasible.

  9. Exercise Session Duration

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    Duration of each completed exercise session, measured in minutes. Higher values indicate longer exercise exposure per session.

  10. Exercise Adherence

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    Adherence to the exercise intervention, calculated as the percentage of completed exercise sessions relative to the number of scheduled exercise sessions: (completed sessions / scheduled sessions) × 100. Higher values indicate greater adherence to the intervention.

Secondary outcomes

  1. Sex

    Time frame: Baseline (Day of admission)

    Participant sex recorded at baseline and categorized as male or female.

  2. Age

    Time frame: Baseline (Day of admission)

    Age of the participant at study enrollment, measured in years.

  3. Type of Hematopoietic Therapy

    Time frame: Baseline (Day of admission)

    Type of hematological treatment received, categorized as autologous hematopoietic stem cell transplantation, allogeneic hematopoietic stem cell transplantation, or chimeric antigen receptor T-cell (CAR-T) therapy.

  4. Hematological Diagnosis

    Time frame: Baseline (Day of admission)

    Primary hematological diagnosis recorded at baseline and classified according to diagnostic category.

  5. Body Mass Index (BMI)

    Time frame: Baseline (Day of admission)

    Body mass index calculated as weight in kilograms divided by height in meters squared (kg/m²). Higher values indicate greater body mass relative to height.

  6. 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)

    Anxiety symptoms assessed using the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A). Scores range from 0 to 21, with higher scores indicating greater anxiety symptoms.

  7. 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)

    Depressive symptoms assessed using the Hospital Anxiety and Depression Scale-Depression subscale (HADS-D). Scores range from 0 to 21, with higher scores indicating greater depressive symptoms.

  8. 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)

    Health-related quality of life assessed using the EORTC QLQ-C30 questionnaire. Scores are transformed to a 0-100 scale according to EORTC scoring procedures. Higher scores on the global health status and functional scales indicate better quality of life, whereas higher scores on symptom scales indicate greater symptom burden.

  9. 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)

    Quality of life related to bone marrow transplantation assessed using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. Higher scores indicate better quality of life and well-being.

  10. Pain Intensity (Visual Analog Scale, VAS)

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    Pain intensity assessed using the Visual Analog Scale (VAS). Participants rate their perceived pain on a scale from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain.

  11. Analgesic Treatment Level

    Time frame: During hospitalization (from day 1 to hospital discharge, 28 days ± 2 weeks)

    Type of analgesic treatment prescribed according to the analgesic ladder classification: Level I (non-opioid analgesics), Level II (weak opioids), Level III (strong opioids), and Level IV (advanced analgesic interventions).

  12. Simulator Sickness Questionnaire (SSQ) Score

    Time frame: During intervention, Intermediate assessment and hospital discharge (from day 1 to hospital discharge, 28 days±2 weeks)

    Simulator sickness symptoms assessed using the Simulator Sickness Questionnaire (SSQ). The total score ranges from 0 to 48, with higher scores indicating greater severity of simulator sickness symptoms.

  13. Game Experience Questionnaire (GEQ) Score

    Time frame: Intermediate assessment and hospital discharge (from day 1 to hospital discharge, 28 days±2 weeks)

    User experience during the game-based intervention assessed using the Game Experience Questionnaire (GEQ). The questionnaire evaluates four dimensions: Positive Experiences (mean score of items 1, 5, 7, 8, 12, and 16), Negative Experiences (mean score of items 2, 4, 6, 11, 14, and 15), Fatigue (mean score of items 10 and 13), and Return to Reality (mean score of items 3, 9, and 17). Each subscale is scored from 0 to 4, with higher scores indicating greater intensity of the corresponding experience.

  14. Satisfaction with the Immersive Virtual Reality (IVR) Intervention

    Time frame: Intermediate assessment and hospital discharge (from day 1 to hospital discharge, 28 days±2 weeks)

    Participant satisfaction with the immersive virtual reality (IVR) intervention assessed using an ad hoc satisfaction questionnaire. The questionnaire evaluates overall experience, perceived positive and negative aspects, willingness to repeat the intervention, recommendation of the intervention to others, and perceived usefulness of the intervention. Responses include qualitative feedback and categorical responses (yes/no). Higher satisfaction is indicated by positive responses regarding the experience, willingness to repeat, recommendation, and perceived usefulness.

  15. Characteristics of Adverse Events

    Time frame: During the intervention (from day 1 to hospital discharge, 28 days±2 weeks)

    Characteristics of adverse events occurring during the intervention, including type of event (exercise-related, immersive virtual reality [IVR]-related, or other), severity (mild, moderate, or severe), and causal relationship with the intervention (not related, possibly related, or probably related).

  16. Perceived Exertion (Modified Borg Scale)

    Time frame: After each exercise session (from day 1 to hospital discharge, 28 days±2 weeks)

    Perceived exertion during exercise sessions assessed using the Modified Borg Rating of Perceived Exertion Scale. Scores range from 1 to 10, with higher scores indicating greater perceived effort during exercise.

  17. Exercise Adherence During Follow-up

    Time frame: Follow-up (3 months ± 2 weeks)

    Adherence to the prescribed exercise program during the 3-month follow-up period. Adherence is calculated based on frequency adherence (FA = completed exercise sessions / prescribed exercise sessions × 100), duration adherence (DA = completed average session duration / prescribed session duration × 100), and global adherence (GA = [FA + DA] / 2). Adherence is categorized as low (<50%), moderate (51-79%), or high (≥80%).

  18. Exercise Program Dropout Rate

    Time frame: Follow-up (3 months ± 2 weeks)

    Proportion of participants who discontinued the exercise program during the 3-month follow-up period. Dropout rate is calculated as: (number of initiated but not completed sessions / total prescribed sessions) × 100.

Study contacts

Contact information is provided by the study sponsor or research team.

Carmen Albo López, MD

CONTACT

[email protected]

986 217 832

Sponsors and collaborators

Lead sponsor

Fundacin Biomedica Galicia Sur

Other

Registry information

Acronym: RVI-ET

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Jul 1, 2026
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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