Non-invasive brain stimulation on functional capacity in prefrail older adults: a protocol for a randomised clinical...

Therapeutic physical exercise (TPE) is considered the cornerstone intervention to prevent or reverse frailty; however, prefrail individuals often face challenges achieving the exercise intensity required to induce multisystem adaptations. Non-invasive neuromodulation techniques-including virtual running-based visual illusion (VR) and, transcranial direct current stimulation (tDCS),-have shown promising effects on neuroplasticity, motor performance and executive function. The primary objective of this study is to compare the effect of adding two neuromodulation strategies to a multicomponent TPE programme on functional capacity and quality of life in prefrail older adults.

This four-arm, triple-blinded randomized controlled trial will include adults aged ≥ 65 years classified as prefrail according to Fried criteria. Participants will be randomly assigned to one of the following groups: VR+TPE, sham VR+TPE, tDCS+TPE or, sham tDCS+TPE. All interventions will be applied during an 8 week-programme consisting of 24 supervised sessions. The primary outcomes will be frailty status (Fried Phenotype) and walking speed. Secondary outcomes will include neuroplasticity biomarkers (plasma BDNF), heart rate variability, upper and lower limb isometric strength, quality of life (EQ 5D 5L), lower-limb muscle power, static and dynamic functionality, gait quality and dual-task performance. Assessments will be conducted at baseline, immediately after the first session, at 4 weeks, at the end of the 8 week intervention, and at 4 week follow up.

The study has received approval from the Ethics Committee of Research in Humans of the University of Valencia (2025-FIS-4007899). All participants will provide written informed consent before enrolment. Study findings will be disseminated through peer reviewed publications, scientific conferences and participant summaries.

https://clinicaltrials.gov/study/NCT07346989?cond=NCT07346989&viewType=Card&rank=1, identifier NCT07346989.