{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:53:58Z","timestamp":1781240038238,"version":"3.54.1"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Subtle neurodegenerative motor and cognitive impairments accumulate over a prodromal period several years before clinical diagnosis of Huntington's disease (HD). The inclusion of prodromal individuals in therapeutic trials would facilitate testing of therapies early in the disease course and the development of treatments intended to prevent or delay disability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We evaluate the normalized prognostic index (PIN) score as a tool to select participants for a perimanifest trial. We explore anticipated PIN\u2010based inclusion rates from the preHD screening population and estimate sample\u2010size requirements based on PIN threshold, trial duration, and outcome measure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Individual participant data from ENROLL\u2010HD were used to fit mixed effect linear models to assess longitudinal changes in clinical metrics for participants with early\u2010manifest HD and PIN\u2010stratified preHD subcohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A PIN threshold of 0.0 was met by 40% of the preHD participants in ENROLL\u2010HD; 39.4% and 55.2% progressed to new diagnoses of early\u2010manifest HD within 2 and 3\u2009years, respectively. Various PIN thresholds also enabled the selection of specified ratios of prodromal preHD to early manifest HD participants for a perimanifest trial. Estimated sample sizes for a trial enrolling prodromal preHD (PIN\u2009&gt;\u20090.0) and stage 1 and 2 motor\u2010diagnosed participants varied depending on the composition of the screening pool, the length of follow\u2010up (1, 2, or 3\u2009years), and outcome measure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The composition of a perimanifest clinical trial population can be defined using preselected PIN thresholds, facilitating the assessment of potential disease\u2010modifying therapies in HD. \u00a9 2022 Voyager Therapeutics, Inc. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28944","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T03:12:40Z","timestamp":1644981160000},"page":"1040-1046","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Utility of the Huntington's Disease Prognostic Index Score for a Perimanifest Clinical Trial"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-4679","authenticated-orcid":false,"given":"Douglas R.","family":"Langbehn","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Iowa Carver College of Medicine, Psychiatry Research  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth M.","family":"Fine","sequence":"additional","affiliation":[{"name":"Voyager Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Meier","sequence":"additional","affiliation":[{"name":"Voyager Therapeutics, Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Hersch","sequence":"additional","affiliation":[{"name":"Voyager Therapeutics, Inc.  Cambridge Massachusetts USA"},{"name":"Eisai Inc.  Woodcliff Lake New Jersey USA"},{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70088-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70238-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.2736"},{"key":"e_1_2_9_5_1","volume-title":"Huntington's Disease","author":"Wild EJ","year":"2013"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26011"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28222"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000187"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25835"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-189003"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2368"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26838"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12388"},{"key":"e_1_2_9_14_1","unstructured":"InvegarSustennar(paliperidone palmate) extended\u2010release injectable suspension. Prescribing information. Janssen\u2010Division of Ortho\u2010McNeil\u2010Janssen Pharmaceuticals Inc.;2010."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029522"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28944","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.28944","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28944","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:23:25Z","timestamp":1760963005000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.28944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/mds.28944"],"URL":"https:\/\/doi.org\/10.1002\/mds.28944","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,16]]},"assertion":[{"value":"2021-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}