Phenotyping Rehabilitation for Improving Frailty, Functional Capacity

Chronic venous insufficiency (CVI) is a common progressive vascular disorder affecting a substantial proportion of older adults. The condition is characterized by venous hypertension resulting from venous valvular dysfunction and/or venous outflow obstruction, leading to symptoms such as leg pain, heaviness, edema, fatigue, reduced mobility, and impaired quality of life. Although exercise-based rehabilitation has demonstrated benefits for calf muscle pump function and venous circulation, the broader impact of rehabilitation on frailty, physical performance, and functional decline remains insufficiently explored.

Older adults with CVI frequently present with age-related impairments including sarcopenia, muscle weakness, balance deficits, and reduced mobility. These impairments may contribute to deterioration in calf muscle pump performance and worsening venous symptoms, while venous symptoms themselves may reduce physical activity participation, creating a cycle of functional decline and disease progression. Frailty is increasingly recognized as an important predictor of disability, falls, hospitalization, and mortality in older adults; however, it has rarely been targeted within CVI rehabilitation programs.

This study introduces a novel rehabilitation model termed Performance-Based Phenotyping for Precision Physiotherapy, in which rehabilitation interventions are individualized according to participants' dominant functional deficits identified through objective performance-based assessments. Following a standardized functional assessment battery, participants allocated to the experimental group will be categorized into predefined phenotypes reflecting strength deficits, mobility and fall-related impairments, lower-limb power limitations, or mixed functional impairments. Each phenotype will receive a rehabilitation program specifically tailored to its dominant impairment profile while maintaining common CVI-related rehabilitation components.

The study will be conducted as a prospective, assessor-blinded, parallel-group randomized controlled trial. Community-dwelling adults aged 60 years and older with physician-confirmed chronic venous insufficiency (CEAP stages C2-C5) and elevated risk of sarcopenia or functional decline (SARC-F score ≥4) will be recruited and randomly assigned in a 1:1 ratio to either individualized phenotype-based rehabilitation or standardized multicomponent rehabilitation. Both groups will participate in supervised rehabilitation sessions three times per week for 12 weeks, with each session lasting approximately 60 minutes. Participants will then be followed for an additional 12 weeks to assess the durability of treatment effects.

The primary outcome will be physical performance assessed using the Short Physical Performance Battery (SPPB). Secondary outcomes will include frailty status measured by the Fried Frailty Phenotype, mobility assessed by the Timed Up and Go Test, sarcopenia-related measures including handgrip strength and the Five Times Sit-to-Stand Test, functional capacity measured by the Six-Minute Walk Test, venous outcomes including the Venous Clinical Severity Score (VCSS), limb circumference and leg heaviness, and health-related quality of life measured using the CIVIQ-14 questionnaire. Outcomes will be assessed at baseline, post-intervention (12 weeks), and follow-up (12 weeks).

The investigators hypothesize that individualized rehabilitation guided by performance-based phenotyping will result in greater improvements in physical performance, frailty, mobility, functional capacity, venous symptoms, and quality of life compared with a standardized rehabilitation approach. This study may provide evidence supporting precision rehabilitation strategies for older adults with chronic venous insufficiency and contribute to the development of more targeted physiotherapy interventions for this growing population.