Virtual Reality Training Dose for Arm Recovery After Stroke: Clinical and Blood Biomarker Responses
Prospective Monitoring of Neuroplastic Effects in Stroke Rehabilitation: Long-term Recovery Prognosis and Therapy Optimization Via Biomarkers
The goal of this clinical trial is to learn whether adding virtual reality (VR) training to conventional rehabilitation improves arm movement in adults who had a stroke 6 to 24 months earlier, and whether VR training 5 days a week gives more benefit than VR training 2 days a week. The study will also measure three blood markers that may reflect brain and muscle adaptation (BDNF, irisin and S100B).
The main questions it aims to answer are:
- Does arm motor function, measured with the Fugl-Meyer Assessment for Upper Extremity 12 weeks after the start of treatment, improve more when VR training is added to conventional rehabilitation, and does it improve more with 5 than with 2 VR sessions a week?
- As an exploratory question, do blood levels of BDNF, irisin and S100B change differently between the groups, and are these changes related to the improvement in arm function?
Researchers will compare three groups: conventional rehabilitation alone, conventional rehabilitation plus VR training 2 days a week, and conventional rehabilitation plus VR training 5 days a week.
Participants will:
- Be assigned by chance to one of the three groups
- Receive conventional rehabilitation for 45 minutes, 5 days a week, for 4 weeks; depending on their group, they will also receive 30-minute VR sessions with the Neuroforma system 2 or 5 days a week
- Follow a home exercise program from week 4 to week 12
- Have arm function tests and a fasting morning blood sample at the start of the study, at week 4 and at week 12
Przegląd badań
Status
Warunki
Szczegółowy opis
Background Upper-limb motor impairment persists in many people after stroke. Virtual reality (VR)-based training added to conventional rehabilitation can improve upper-limb function, but the amount (dose) of VR training needed and the biological processes that accompany recovery are unclear.
Design Prospective, single-center, randomized (1:1:1), assessor-blinded, three-arm, parallel-group dose-response trial in 72 adults 6 to 24 months after ischemic or hemorrhagic stroke with moderate-to-severe upper-limb motor impairment (Fugl-Meyer Assessment for Upper Extremity [FMA-UE] motor score 15 to 50).
Randomization and blinding A computer-generated block randomization list will be prepared by an independent researcher who is not involved in recruitment, treatment or assessment; allocation will be concealed in sealed opaque envelopes. Participants and treating clinicians cannot be blinded. The outcome assessor, the laboratory staff performing the biomarker assays and the statistician will be unaware of group allocation.
Interventions (4 weeks) All participants receive conventional rehabilitation for 45 minutes per session, 5 days per week (neurodevelopmental approaches, functional upper-limb exercises, task-oriented training, stretching and strengthening). The low-dose VR group additionally receives 30-minute Neuroforma VR sessions 2 days per week (8 sessions), and the high-dose VR group 5 days per week (20 sessions). Scheduled therapy time is therefore 225, 285 and 375 minutes per week in the control, low-dose and high-dose groups. From week 4 to week 12, all participants follow the same standardized home exercise program. Adherence and adverse events, including cybersickness, are recorded daily during the intervention.
Assessments At baseline, week 4 (end of the intervention) and week 12 (8 weeks after the end of the intervention), the blinded assessor administers the FMA-UE, the Wolf Motor Function Test (WMFT) and the Action Research Arm Test (ARAT). Fasting venous blood is drawn between 08:00 and 10:00 at the same visits; serum is separated by centrifugation, stored at -80 °C and analyzed in batches with commercial ELISA kits for BDNF, irisin (FNDC5) and S100B.
Statistical analysis Analyses follow the intention-to-treat principle. The primary outcome, change in FMA-UE from baseline to week 12, is compared between groups with a linear mixed-effects model for repeated measures (weeks 4 and 12) adjusted for baseline FMA-UE; pairwise group comparisons are Bonferroni-adjusted. Secondary clinical outcomes are analyzed in the same way. The sample size of 36 required for the primary outcome (repeated-measures ANOVA, group-by-time interaction, f = 0.25, alpha = 0.05, power = 0.80, correlation among repeated measures = 0.50) was increased to 72 to allow pairwise dose comparisons and exploratory biomarker analyses and to cover an expected attrition of 20%.
Exploratory analyses Biomarker outcomes are exploratory; no adjustment for multiple comparisons will be made, and results will be interpreted as hypothesis-generating. Associations between changes in clinical scores and biomarker levels will be examined with correlation analysis. ROC analysis will assess whether biomarker changes identify participants who reach a clinically meaningful FMA-UE improvement (at least 5.25 points). A classification and regression tree (CART) model using baseline and week-4 clinical and biomarker data will be developed to predict treatment response and internally validated with 10-fold cross-validation; external validation is not part of this study. A model-based cost analysis will estimate the potential savings of response-guided treatment duration compared with a fixed 4-week program. These analyses are hypothesis-generating.
Funding Health Institutes of Türkiye (TÜSEB), project number 51841.
Typ studiów
Zapisy (Szacowany)
Faza
- Nie dotyczy
Kontakty i lokalizacje
Kontakt w sprawie studiów
- Nazwa: Barış Yenen, MD, Assistant Professor
- Numer telefonu: 0090 5383121951
- E-mail: baris.yenen@ksbu.edu.tr
Kopia zapasowa kontaktu do badania
- Nazwa: Melike Şimşir Yenen, MD
- Numer telefonu: 0090 5055222918
- E-mail: drmelikesimsiryenen@gmail.com
Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
Inclusion Criteria:
- Age 18 to 75 years
- Ischemic or hemorrhagic stroke confirmed by computed tomography or magnetic resonance imaging
- 6 to 24 months since stroke onset
- Upper-extremity motor impairment, Brunnstrom stage 2 to 4
- Fugl-Meyer Assessment for Upper Extremity motor score 15 to 50
- Montreal Cognitive Assessment (MoCA) score of 21 or higher
- Vision and hearing sufficient to interact with the virtual reality system
- Able to give written informed consent
Exclusion Criteria:
- Bilateral hemispheric involvement
- Severe unilateral spatial neglect or global aphasia
- Uncontrolled epilepsy
- Active upper-extremity pain (visual analog scale 7/10 or higher) or severe spasticity limiting movement (Modified Ashworth Scale 3 or higher)
- Botulinum toxin injection within the previous 3 months
- Severe cardiovascular instability or a contraindication to exercise
- History of cybersickness induced by virtual reality
- Concurrent participation in another experimental rehabilitation program
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Pojedynczy
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
|---|---|
|
Aktywny komparator: Conventional Rehabilitation
Conventional rehabilitation, 45 minutes per session, 5 days per week for 4 weeks (20 sessions): neurodevelopmental approaches, functional upper-limb exercises, task-oriented training, and stretching and strengthening exercises. From week 4 to week 12: standardized home exercise program. Intervention: Conventional rehabilitation program; Home exercise program |
45 minutes per session, 5 days per week for 4 weeks: neurodevelopmental approaches, functional upper-limb exercises, task-oriented training, and stretching and strengthening exercises. Standardized home exercise program given to all participants from week 4 to week 12. |
|
Eksperymentalny: Low-Dose VR: Conventional Rehabilitation + VR 2 Days/Week
Conventional rehabilitation as in the control arm plus Neuroforma virtual reality training, 30 minutes per session, 2 days per week for 4 weeks (8 sessions). From week 4 to week 12: the same standardized home exercise program. Intervention: Neuroforma virtual reality training; Conventional rehabilitation program; Home exercise program |
45 minutes per session, 5 days per week for 4 weeks: neurodevelopmental approaches, functional upper-limb exercises, task-oriented training, and stretching and strengthening exercises. Standardized home exercise program given to all participants from week 4 to week 12. Upper-limb training with the Neuroforma virtual reality system, 30 minutes per session: mirror-therapy modules with visual feedback, gamified cognitive-motor tasks requiring hand-arm coordination, and repetitive movement practice. Session duration is increased gradually at the start and shortened if cybersickness symptoms are severe. |
|
Eksperymentalny: High-Dose VR: Conventional Rehabilitation + VR 5 Days/Week
Conventional rehabilitation as in the control arm plus Neuroforma virtual reality training, 30 minutes per session, 5 days per week for 4 weeks (20 sessions). From week 4 to week 12: the same standardized home exercise program. Intervention: Neuroforma virtual reality training; Conventional rehabilitation program; Home exercise program |
45 minutes per session, 5 days per week for 4 weeks: neurodevelopmental approaches, functional upper-limb exercises, task-oriented training, and stretching and strengthening exercises. Standardized home exercise program given to all participants from week 4 to week 12. Upper-limb training with the Neuroforma virtual reality system, 30 minutes per session: mirror-therapy modules with visual feedback, gamified cognitive-motor tasks requiring hand-arm coordination, and repetitive movement practice. Session duration is increased gradually at the start and shortened if cybersickness symptoms are severe. |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Change in Fugl-Meyer Assessment for Upper Extremity (FMA-UE) Motor Score From Baseline to Week 12
Ramy czasowe: Baseline and week 12 (8 weeks after the end of the 4-week intervention)
|
Upper-limb motor impairment measured with the motor domain of the FMA-UE (33 items scored 0 to 2; total 0 to 66, higher scores indicate better motor function), administered by an assessor blinded to group allocation. Change = week-12 score minus baseline score. |
Baseline and week 12 (8 weeks after the end of the 4-week intervention)
|
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Change in FMA-UE Motor Score From Baseline to Week 4
Ramy czasowe: Baseline and week 4 (end of the intervention)
|
FMA-UE motor domain (0 to 66; higher scores indicate better motor function), blinded assessor. Change = week-4 score minus baseline score. |
Baseline and week 4 (end of the intervention)
|
|
Change in Wolf Motor Function Test Functional Ability Scale (WMFT-FAS) Score
Ramy czasowe: Baseline, week 4 and week 12
|
Quality of movement rated 0 to 5 on each of the 15 timed WMFT tasks (total 0 to 75; higher scores indicate better upper-limb function), blinded assessor. |
Baseline, week 4 and week 12
|
|
Change in Wolf Motor Function Test Performance Time
Ramy czasowe: Baseline, week 4 and week 12
|
Mean time in seconds to complete the 15 timed WMFT tasks (each task capped at 120 seconds); lower values indicate better performance. Blinded assessor. |
Baseline, week 4 and week 12
|
|
Change in Action Research Arm Test (ARAT) Score
Ramy czasowe: Baseline, week 4 and week 12
|
19 items in 4 subtests (grasp, grip, pinch, gross movement), each scored 0 to 3; total 0 to 57, higher scores indicate better upper-limb function. Blinded assessor. |
Baseline, week 4 and week 12
|
Inne miary wyników
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Change in Serum Brain-Derived Neurotrophic Factor (BDNF) Concentration (Exploratory)
Ramy czasowe: Baseline, week 4 and week 12
|
Fasting venous blood drawn between 08:00 and 10:00; serum stored at -80 °C and measured in batches with a commercial ELISA kit by laboratory staff blinded to group allocation. Exploratory outcome. |
Baseline, week 4 and week 12
|
|
Change in Serum Irisin Concentration (Exploratory)
Ramy czasowe: Baseline, week 4 and week 12
|
Fasting venous blood drawn between 08:00 and 10:00; serum stored at -80 °C and measured in batches with a commercial ELISA kit by laboratory staff blinded to group allocation. Exploratory outcome. |
Baseline, week 4 and week 12
|
|
Change in Serum S100B Concentration (Exploratory)
Ramy czasowe: Baseline, week 4 and week 12
|
Fasting venous blood drawn between 08:00 and 10:00; serum stored at -80 °C and measured in batches with a commercial ELISA kit by laboratory staff blinded to group allocation. Exploratory outcome. |
Baseline, week 4 and week 12
|
|
Number of Participants With Adverse Events, Including Cybersickness
Ramy czasowe: Baseline to week 12
|
Adverse events and cybersickness symptoms recorded daily during the 4-week intervention and at each follow-up visit. |
Baseline to week 12
|
|
Adherence to the Allocated Intervention
Ramy czasowe: Baseline to week 4
|
Percentage of scheduled conventional rehabilitation and VR sessions completed. |
Baseline to week 4
|
Współpracownicy i badacze
Śledczy
- Główny śledczy: Barış Yenen, MD, Assistant Professor, Kutahya Health Sciences University
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Szacowany)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- TUSEB-51841
- 51841 (Inny numer grantu/finansowania: TÜSEB)
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu IPD
De-identified individual participant data underlying the results reported in publications (baseline characteristics, FMA-UE, WMFT and ARAT scores, serum BDNF, irisin and S100B concentrations, and group allocation) will be shared upon reasonable request, together with a data dictionary.
Ramy czasowe udostępniania IPD
Beginning 6 months after publication of the primary results and ending 5 years after publication.
Kryteria dostępu do udostępniania IPD
Requests from researchers with a methodologically sound proposal should be sent to the principal investigator. Data will be shared after approval by the Kütahya Health Sciences University Clinical Research Ethics Committee and under a data use agreement, in accordance with the Turkish Personal Data Protection Law (No. 6698).
Typ informacji pomocniczych dotyczących udostępniania IPD
- PROTOKÓŁ BADANIA
- ICF
- ANALITYCZNY_KOD
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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