{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:58:41Z","timestamp":1790441921369,"version":"4.1.0"},"reference-count":35,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"abstract":"<jats:p>Late-stage Parkinson's disease (LSPD) represents an under-recognized and under-studied phase of PD characterized by severe axial motor symptoms, high non-motor burden, cognitive impairment, functional dependence, and substantial caregiver involvement. Despite its major clinical and socioeconomic impact, LSPD seem to be largely excluded from clinical trials, likely due to advanced disability, mobility limitations, and the lack of appropriately adapted outcome measures.<\/jats:p>\n                  <jats:p>To better characterize the representation of this population in research, we conducted a systematic review of clinical trials listed in major clinical trials registries, focusing on studies that included participants with a Hoehn and Yahr stage of 4 or 5. As of January 2026, 353 registered trials allowed inclusion of individuals with LSPD; however, many of these studies applied exclusion criteria related to dementia. Most trials investigated pharmacological or rehabilitation interventions targeting axial or global motor symptoms. Among the published studies (27.8% of the total), only 30% actually enrolled participants with LSPD.<\/jats:p>\n                  <jats:p>Our findings confirm the limited inclusion of individuals with LSPD in clinical research. Broadening eligibility criteria, implementing decentralized or home-based trial designs, incorporating caregiver-centered outcomes, and adopting cognitively adapted assessment tools may foster a more inclusive and patient-centered research framework. Such efforts are essential to better address the needs of this growing and vulnerable population.<\/jats:p>","DOI":"10.1177\/1877718x261491591","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:53:51Z","timestamp":1790074431000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical trials in late-stage Parkinson's disease"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-592X","authenticated-orcid":false,"given":"Margherita","family":"Fabbri","sequence":"first","affiliation":[{"name":"Toulouse NeuroToul Center of Excellence in Neurodegeneration, French NS-Park\/F-CRIN Network, University of Toulouse, CHU of Toulouse, INSERM"},{"name":"CHU de Toulouse"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7223-2060","authenticated-orcid":false,"given":"Silvia","family":"Gallo","sequence":"additional","affiliation":[{"name":"Toulouse NeuroToul Center of Excellence in Neurodegeneration, French NS-Park\/F-CRIN Network, University of Toulouse, CHU of Toulouse, INSERM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8930-4382","authenticated-orcid":false,"given":"Tiago","family":"Machado","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade de Lisboa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Pacilio","sequence":"additional","affiliation":[{"name":"CHU de Toulouse"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Rascol","sequence":"additional","affiliation":[{"name":"Toulouse NeuroToul Center of Excellence in Neurodegeneration, French NS-Park\/F-CRIN Network, University of Toulouse, CHU of Toulouse, INSERM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-5113","authenticated-orcid":false,"given":"Joaquim J","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade de Lisboa"},{"name":"Unidade Local de Sa\u00fade de Santa Maria, Lisboa, Portugal"},{"name":"CNS-Campus Neurol\u00f3gico, Torres Vedras, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.126"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2018.1502165"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2012.03866.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29066"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27372"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30162"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","DOI":"10.3233\/JPD-202096","article-title":"Challenges and perspectives in the management of late-stage Parkinson\u2019s disease","volume":"10","author":"Fabbri M","year":"2020","unstructured":"Fabbri M, Kauppila LA, Ferreira JJ, et al. Challenges and perspectives in the management of late-stage Parkinson\u2019s disease. Journal of Parkinson\u2019s Disease 2020; 10: S75\u2013s83.","journal-title":"Journal of Parkinson\u2019s Disease"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm142"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2020.05.016"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2025.107949"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29718"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-021-01011-y"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29900"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","DOI":"10.3233\/JPD-181474","article-title":"The emerging evidence of the Parkinson pandemic","volume":"8","author":"Dorsey ER","year":"2018","unstructured":"Dorsey ER, Sherer T, Okun MS, et al. 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