{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:30:28Z","timestamp":1782235828489,"version":"3.54.5"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Challenger Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The conventional clinical trial design in Alzheimer\u2019s disease (AD) and AD-related disorders (ADRDs) is the parallel-group randomized controlled trial. However, in heterogeneous disorders like AD\/ADRDs, this design requires large sample sizes to detect meaningful effects in an \u201caverage\u201d patient. They are very costly and, despite many attempts, have not yielded new treatments for many years. An alternative, the multi-crossover, randomized control trial (MCRCT) is a design in which each patient serves as their own control across successive, randomized blocks of active treatment and placebo. This design overcomes many limitations of parallel-group trials, yielding an unbiased assessment of treatment effect at the individual level (\u201cN-of-1\u201d) regardless of unique patient characteristics. The goal of the present study is to pilot a MCRCT of a potential symptomatic treatment, methylphenidate, for mild-stage AD\/ADRDs, testing feasibility and compliance of participants in this design and efficacy of the drug using both standard and novel outcome measures suited for this design.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Ten participants with mild cognitive impairment or mild-stage dementia due to AD\/ADRDs will undergo a 4-week lead-in period followed by three, month-long treatment blocks (2\u00a0weeks of treatment with methylphenidate, 2\u00a0weeks placebo in random order). This trial will be conducted entirely virtually with an optional in-person screening visit. The primary outcome of interest is feasibility as measured by compliance and retention, with secondary and exploratory outcomes including cognition as measured by neuropsychological assessment at the end of each treatment period and daily brain games played throughout the study, actigraphy, and neuropsychiatric and functional assessments.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This pilot study will gauge the feasibility of conducting a virtual MCRCT for symptomatic treatment in early AD\/ADRD. It will also compare home-based daily brain games with standard neuropsychological measures within a clinical trial for AD\/ADRD. Particular attention will be paid to compliance, tolerability of drug and participation, learning effects, trends and stability of daily measures across blocks, medication carryover effects, and correlations between standard and brief daily assessments. These data will provide guidance for more efficient trial design and the use of potentially more robust, ecological outcome measures in AD\/ADRD research.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03811847?term=Steven+E.+Arnold&amp;cond=Alzheimer+Disease&amp;draw=2&amp;rank=1\">NCT03811847<\/jats:ext-link>. Registered on 21 January 2019.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-020-04752-x","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T09:03:18Z","timestamp":1607677398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A pilot protocol to assess the feasibility of a virtual multiple crossover, randomized controlled trial design using methylphenidate in mild cognitive impairment"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7185-5810","authenticated-orcid":false,"given":"Libby A.","family":"DesRuisseaux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria J.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison J.","family":"McManus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoopum S.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becky C.","family":"Carlyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Azami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Bolling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn L.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Betensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"issue":"1","key":"4752_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/alzrt155","volume":"5","author":"B Lam","year":"2013","unstructured":"Lam B, Masellis M, Freedman M, Stuss DT, Black SE. 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