Effectiveness of a fully immersive virtual reality-based therapeutic exercise programme with altered visual feedback in patients with fibromyalgia: A study protocol for a randomised controlled trial

STUDY PROTOCOL Effectiveness of a fully immersive virtual reality-based therapeutic exercise programme with altered visual feedback in patients with fibromyalgia: A study protocol for a randomised controlled trial Carlos Salvador-Huerta 1, Jaime Jordán-López1, Pedro Azanon-Nogueira1, Celia García-Lucas1, Juan J. Amer-Cuenca 2*, Juan Francisco Lisón1,3 1 Department of Biomedical Sciences, School of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain, 2 Department of Physiotherapy, School of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain, 3 CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain * Abstract OPEN ACCESS Citation: Salvador-Huerta C, Jordán-López J, Azanon-Nogueira P, García-Lucas C, AmerCuenca JJ, Lisón JF (2026) Effectiveness of a fully immersive virtual reality-based therapeutic exercise programme with altered visual feedback in patients with fibromyalgia: A study protocol for a randomised controlled trial. PLoS One 21(6): e0348346. https://doi.org/10.1371/ journal.pone.0348346 Editor: Hui-Juan Cao, Beijing University of Chinese Medicine, CHINA Received: November 21, 2025 Accepted: April 7, 2026 Published: June 4, 2026 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal. pone.0348346 Copyright: © 2026 Salvador-Huerta et al. This is an open access article distributed under the Fibromyalgia (FM) is a chronic condition characterized by widespread pain, fatigue, and diverse physical and psychological symptoms that significantly impair daily functioning. Latest guidelines advocate for a comprehensive approach to FM management, emphasizing patient education, therapeutic exercise, pharmacological treatments, and psychotherapy. Although exercise remains the primary nonpharmacological strategy supported by robust evidence, its clinical implementation faces several limitations, including poor adherence, fear of movement, pain catastrophizing and proprioceptive deficits. Immersive virtual reality (IVR) has recently emerged as a promising adjunctive tool that not only addresses these limitations but also provides additional therapeutic benefits. Specifically, preliminary studies suggest that incorporating visual feedback manipulation through IVR can effectively modify movement perception, potentially enhancing clinical outcomes. This randomised controlled trial aims to assess the efficacy of a fully immersive virtual reality (FIVR)-based therapeutic exercise programme designed to induce implicit visual illusions, making participants perceive less movement than is performed during structured resistance exercises. Eighty participants diagnosed with FM will be recruited and randomly allocated to either the experimental group, which will engage in a structured resistance exercise regimen combined with FIVR, or the control group, performing identical exercises without FIVR. The primary measure will be the impact of FM on daily life, evaluated using the Revised Fibromyalgia Impact Questionnaire. Secondary outcomes include fatigue, sleep quality, FM symptom severity, health-related quality of life, psychological factors, central sensitization, body perception distortion, lower limb PLOS One | https://doi.org/10.1371/journal.pone.0348346 June 4, 2026 1 / 17 terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data availability statement: No datasets were generated or analysed during the current study, as this manuscript reports a study protocol only. Upon trial completion, the de-identified dataset, accompanying data dictionary, and analysis code will be deposited in Zenodo and made publicly available under an open licence; DOIs will be provided upon release. Funding: This work was supported by the University CEU Cardenal Herrera (GIR25/41). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. strength and handgrip strength, functional mobility, lumbar range of motion, influence of modified visual feedback, behavioural regulation during exercise and overall physical activity levels. This study aims to provide robust evidence regarding the potential benefits of integrating FIVR with therapeutic exercise. Findings could support FIVR as a valuable clinical innovation, potentially yielding superior improvements in daily functioning, physiological outcomes, and psychological well-being compared to traditional exercise interventions alone. ClinicalTrials.gov (NCT06948500). URL: https:// clinicaltrials.gov/ct2/show/NCT06948500. Introduction Fibromyalgia (FM) is a condition of unknown etiology, primarily characterized by the presence of chronic (>3 months) and widespread pain affecting various regions of the body [1]. Although widespread pain is the most distinctive clinical feature, FM is a complex, polysymptomatic disorder that includes other core symptoms such as fatigue and sleep disturbances [2]. In addition to these cardinal symptoms, individuals often experience a range of other symptoms and/or dysfunctions, including cognitive impairments [2], regional pain syndromes, autonomic dysfunction [3], psychiatric symptoms and hypersensitivity to external stimuli [1–3]. FM prevalence significantly varies by diagnostic criteria, remaining underrecognized clinically [4]. Despite this, FM is the second most common rheumatic condition after osteoarthritis [1,4], with a global prevalence of 2%–8% [1,5]. FM substantially impairs quality of life and functional capacity, significantly increasing healthcare demand and costs [6]. Annual costs associated with FM have been estimated at €12,993 million in Spain [5]. In the United States, an estimated economic burden of over US$20 billion annually has been reported [7]. Indirect societal costs, primarily from lost productivity, are also considerable; approximately 24.3% of patients stop working within five years post-diagnosis [8]. Given FM’s clinical complexity and multisystem involvement, a multidisciplinary approach is essential. The latest European League Against Rheumatism (EULAR) guidelines recommend four main pillars for its management: patient education, therapeutic exercise, pharmacological treatment, and psychotherapy [9]. Nonpharmacological strategies should be prioritized, particularly therapeutic exercise remains the first-line intervention, with strong evidence supporting its benefits [9]. High-frequency, high-intensity tr (...truncated)