Hospitalization places older adults at significant risk for hospital-associated disability (HAD), a condition marked by a rapid and often severe decline in muscle strength and function due to immobility. Research has shown that adults aged 65 and older can lose up to 15% of their lower-limb strength within a single week of bed rest, and as much as 5% of muscle mass per day. These declines not only prolong the length of hospital stay but also increase dependence, impair mobility, and elevate the risk of mortality. While high-load resistance training is considered the gold standard for preventing muscle loss, it is often contraindicated or simply unfeasible for frail or post-surgical patients. This creates an urgent need for effective, low-impact alternatives to preserve physical function during hospitalization.
Blood flow restriction (BFR) training has emerged as one such alternative. It works by partially occluding arterial blood flow and fully restricting venous return in a limb using a pressure cuff, thereby enhancing the effects of low-load exercise. BFR has been demonstrated to stimulate muscle hypertrophy and strength gains in various populations, including older adults, and has been shown to be safe in over 300,000 reported clinical sessions. In addition to physical limitations, another major challenge in hospital rehabilitation is poor adherence. Many patients fail to complete unsupervised therapy exercises, largely due to low motivation. Serious games - interactive applications designed with a therapeutic goal - have shown promise in improving engagement, but most are not designed specifically for clinical use or individualized for the needs of hospitalized older adults.
To address these challenges, the GHOSTLY+ system was developed. GHOSTLY+ is a mobile rehabilitation solution combining gamified muscle training with BFR, designed to be used during non-therapy time in hospitalized older adults. The system is based on a serious game app that transforms muscle contractions, measured via surface electromyography (EMG), into in-game actions. By engaging patients in a playful yet physiologically grounded environment, the system aims to increase motivation and ensure proper exercise intensity, even without the use of weights or active movement. GHOSTLY+ includes automated difficulty adjustment based on real-time EMG input and follows evidence-based parameters for strength training: isometric contractions at approximately 75% of each patient's maximum voluntary contraction (MVC), performed three times per session with 12 repetitions each set.
The clinical study described here is a multicenter, randomized controlled trial (RCT) using a Hybrid Type 1 design. The trial will be conducted at three hospitals in Belgium (UZ Brussel, UZ Antwerpen, and UZ Leuven) and will enroll 120 older adults aged 65 years or above who are hospitalized, unable to bear weight or transfer independently, are expected to remain hospitalized for approximately 14 days, and are at high risk of muscle strength loss due to prolonged immobility. Participants will be randomly assigned to one of two groups. The control group will receive standard physiotherapy as prescribed in the hospital. The intervention group will receive standard care supplemented with the GHOSTLY+ system. Participants will use GHOSTLY+ for at least five sessions per week, over two weeks or until discharge, depending on their hospital stay duration.
Each GHOSTLY+ session begins with the application of a smart BFR cuff to the upper thigh of the target leg. The cuff automatically measures the arterial occlusion pressure (AOP) and inflates to 50% of this value, a level known to be effective while minimizing discomfort. Participants are then guided through an in-app calibration process in which they perform three maximal isometric contractions. Based on these readings, the system determines the individual's MVC and sets the game difficulty to 75% of that value. During gameplay, patients must complete three levels per session, with each level representing a set of twelve muscle contractions. Rest periods of two minutes are provided between sets. Based on a previous proof-of-concept study conducted at UZ Brussel (Debeuf et al., 2025), most patients are able to use the system independently after one hour of training. Physiotherapists at each site will be trained to guide this initial setup until patients are independently capable of setting up the GHOSTLY+ system.
The primary outcome of this study is lower-limb muscle strength at hospital discharge, assessed using a handheld MicroFet dynamometer. Secondary outcomes include muscle mass measured via ultrasound imaging of the rectus femoris, functional performance assessed through the 30-second sit-to-stand test and the Functional Ambulation Category, independence in activities of daily living using the Katz scale, time spent bedridden, total length of hospital stay, and patient-reported outcomes related to satisfaction and usability of the intervention. Cognitive status will be assessed using the Mini-Mental State Examination (MMSE), and additional analysis will be performed on EMG data to extract neuromuscular parameters such as signal amplitude and fatigue index. In addition to clinical and physiological data, patients and therapists will participate in implementation data collection via surveys, interviews, and site logbooks, in line with the Consolidated Framework for Implementation Research (CFIR).
Data will be collected at three time points: before the intervention (baseline), at the end of the first week, at the end of two weeks, or at hospital discharge if earlier. Randomization will be performed using a web-based system, with assessors blinded to group allocation to reduce bias. Participants will receive a study-specific ID and will be instructed not to disclose their group assignment to those collecting outcome measures.
Beyond evaluating clinical efficacy, the trial incorporates a robust implementation evaluation. Using the Consolidated Framework for Implementation Research (CFIR) and Proctor's framework, the study will examine key real-world indicators such as acceptability, adoption, fidelity, feasibility, penetration, and sustainability. Data will be gathered through staff surveys, administrative records, structured interviews, app usage data, and focus groups with healthcare professionals and patients. The qualitative data will be analyzed using content analysis and reflexive thematic analysis to identify implementation facilitators and barriers.
The study is powered to detect a 15% difference in lower-limb strength preservation between the intervention and control groups. Analysis will include repeated measures ANOVA, regression modeling, and subgroup analysis to explore the impact of baseline mobility status or cognitive performance. All data will be monitored for quality and completeness, and any serious adverse events will be reported to the competent authorities following the applicable safety guidance under the EU Medical Device Regulation.
Following trial completion, the research team will prepare an implementation package, including an e-learning training module for clinical staff, a Grol & Wensing-based implementation guideline, and a business case for broader adoption. Results will be disseminated through academic publications, clinician workshops, hospital presentations, and patient information campaigns.
In summary, this trial evaluates GHOSTLY+, a novel rehabilitation system combining blood flow restriction and EMG-guided gamified strength training for hospitalized older adults. It is designed to preserve muscle strength, reduce physical decline during bedrest, and boost adherence to therapy using interactive digital technology. By embedding implementation science into its structure, the study aims to not only prove the effectiveness of GHOSTLY+ but also support its sustainable integration into routine hospital care.
