{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:11:40Z","timestamp":1784257900957,"version":"3.55.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 2020-2024"],"award-info":[{"award-number":["Ricerca Corrente 2020-2024"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014805","name":"Roche Italia","doi-asserted-by":"publisher","award":["Bando Roche per la Ricerca Clinica \u2013 A supporto delle figure di Data Manager e Infermieri di Ricerca - Edizione 2022"],"award-info":[{"award-number":["Bando Roche per la Ricerca Clinica \u2013 A supporto delle figure di Data Manager e Infermieri di Ricerca - Edizione 2022"]}],"id":[{"id":"10.13039\/100014805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nBackground<\/jats:title>\nTo date, there has been no medication that has prevented the progression of Parkinson\u2019s disease (PD). Many benefits of intensive and multidisciplinary rehabilitation program for PD are supported by clinical, epidemiological, and experimental data. The main question is whether high-intensity motor and cognitive exercises have an effect on the disease\u2019s biological mechanisms.<\/jats:p>\n<\/jats:sec>\n\nObjective<\/jats:title>\nThis study protocol is a Randomized Controlled Trial (RCT) designed to determine the efficacy of an experimental, intensive, and multidisciplinary treatment in comparison to a home-based self-treatment in improving biomolecular and functional parameters in PD.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nA total of 72 participants will be randomly allocated to two different groups, experimental (n = 36) and control group (n = 36). The rehabilitation program will last 6 consecutive weeks and will involve the execution of a total of 30 sessions, one for each day of the week from Monday to Friday. Participants allocated to the control group will carry out a home-based self-treatment program that includes muscle-stretching and active mobilization exercises for 40\u2019\/day for 6 consecutive weeks. The primary outcome measure is the effects of both treatments on a new set of molecular biomarkers such as oligomeric alpha-synuclein and neurotrophic factors measured in peripheral neural derived extracellular vesicles (NDEVs). Secondary outcomes will include changes of motor and non-motor symptoms, balance and gait performance and cognitive functioning. This RCT has been registered as \u201cIntensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson\u2019s Disease\u201d on 30 May, 2022 to ClinicalTrials.gov with the Study ID number: NCT05452655.<\/jats:p>\n<\/jats:sec>\n\nDiscussion<\/jats:title>\nThis rehabilitation program is believed to be crucial in modifying biomolecular and functional parameters in people with PD. We expect that this study will provide additional evidence to understand the impact of an aerobic and intensive rehabilitation program on brain plasticity in patients with PD.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0309405","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T17:36:13Z","timestamp":1729704973000},"page":"e0309405","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigating the effects of a daily multidisciplinary intensive outpatient rehabilitation program on innovative biomarkers in people with Parkinson\u2019s disease: Study protocol for a phase III randomized controlled clinical trial"],"prefix":"10.1371","volume":"19","author":[{"given":"Francesca 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