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Modafinil modulates beta\/gamma band activity in the pedunculopontine nucleus (PPN), like PPN deep brain stimulation. We therefore tested the hypothesis that Modafinil would improve FOG in PwPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PwPD with FOG were randomized to early\u2010start (24\u2009weeks modafinil) or delayed\u2010start (12\u2009weeks each, placebo then modafinil) of oral modafinil 50\u2009mg, followed by a 2\u2010week washout for both arms. Primary outcomes were change in OFF\u2010levodopa stride length and FOG questionnaire scores; secondary outcomes were change in motor Unified Parkinson's Disease Rating Scale (UPDRS), sleep and quality\u2010of\u2010life scores, and post hoc outcome was change in percent freezing time (%FT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Early\u2010 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912) and delayed\u2010start (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099) group participants were well matched for age, OFF\u2010levodopa motor UPDRS and FOG\u2010Q scores. Primary and secondary outcomes did not reach statistical significance. Limiting the analysis to study completers with quantifiable visualized freezing at the initial visit and collapsing the two study arms (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911), %FT trended to improvement with 50\u2009mg modafinil in 8\/11 participants (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.15) and worsening after 2\u2009weeks washout in 9\/11 participants (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.09). A future cross\u2010over study with 50 participants would have 0.80 power to detect a 0.5 standard\u2010deviation improvement in %FT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>For future therapeutic trials, selecting PwPD with moderate, quantifiable FOG and utilizing appropriate outcome measures like %FT will improve the ability to identify intervention effects. Even for short trials, analyses must account for gait decline. An FOG outcome measure that requires less analysis time burden than video quantification, and the ability for at\u2010home monitoring is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70276","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T04:05:11Z","timestamp":1765253111000},"page":"899-910","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lessons Learned From a Delayed\u2010Start Trial of Modafinil for Freezing of Gait in Parkinson's Disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-2020","authenticated-orcid":false,"given":"Tuhin","family":"Virmani","sequence":"first","affiliation":[{"name":"Department of Neurology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"},{"name":"Department of Biomedical Informatics University of Arkansas for Medical Sciences  Little Rock Arkansas 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