Feasibility and acceptability of Strengthening Mental Abilities with Relational Training (SMART) for cognitive difficulties in multiple sclerosis: a randomised controlled trial

Feasibility and acceptability of Strengthening Mental Abilities with Relational Training (SMART) for cognitive difficulties in multiple sclerosis: a randomised controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Feasibility and acceptability of Strengthening Mental Abilities with Relational Training (SMART) for cognitive difficulties in multiple sclerosis: a randomised controlled trial Nima Golijani-Moghaddam, David L. Dawson, Nikos Evangelou, James Turton, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8086622/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Cognitive difficulties are common in multiple sclerosis (MS) and are associated with poorer quality of life, reduced independence, and lower employment. Despite growing interest in cognitive rehabilitation, existing interventions often lack generalisability and accessibility. Strengthening Mental Abilities with Relational Training (SMART) is a digital intervention targeting relational skills, which are theorised to underpin broader cognitive functioning. This trial evaluated the feasibility, acceptability, and preliminary signals of efficacy of SMART for people with MS experiencing cognitive difficulties. Methods: We conducted a three-arm parallel-group feasibility randomised controlled trial. Participants with a diagnosis of MS and self-reported cognitive problems were recruited from three NHS sites and randomised (1:1:1) to SMART plus treatment-as-usual (TAU), Active control (Sudoku) plus TAU, or TAU alone. Primary feasibility outcomes included recruitment, retention, intervention adherence, and data completeness. Acceptability was assessed using intervention-usage data and participant feedback. Candidate outcome measures included the Perceived Deficits Questionnaire (PDQ), Symbol Digit Modalities Test (SDMT), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), EQ-5D-5L, and ICECAP-A. Assessments took place at baseline, 3 months, and 6 months. The study was co-developed with people living with MS and their families through embedded patient and public involvement and engagement processes. Results: A total of 43 participants were randomised (72% of target). Retention was 84% at 3-month follow-up and 77% at 6 months. SMART adherence was high, with 93% of participants meeting the predefined criterion for training adherence. Acceptability feedback was consistently positive across arms. Data completeness for self-report and performance outcomes was acceptable (typically 60–80% across measures), though return rates for RBANS were lower due to postal logistics. Exploratory analysis suggested a moderate effect of SMART on perceived cognitive difficulties (PDQ, Cohen’s d = 0.85 vs Active control; 0.69 vs TAU), with confidence intervals supporting the possibility of a clinically meaningful benefit. No clear between-group signal was observed on the SDMT. Conclusions: Trial procedures were feasible, and the SMART intervention was acceptable to people with MS. Findings support progression to a fully powered trial, with minor refinements to recruitment and assessment processes. Trial Registration: Registration ID: ClinicalTrials.gov: NCT04975685 – registered on July 23rd, 2021 Multiple Sclerosis Cognitive Rehabilitation Feasibility Randomised Controlled Trial Relational Training Full Text Additional Declarations Competing interest reported. BR was involved in developing the SMART software for commercial purposes. Software was provided gratis for the purpose of this study. BR was not involved in the reported data analysis. RdN has received funding from Novartis, Biogen, and Merck 709 (speakers’ bureau) to deliver lectures on cognition and MS. The authors declare that they have no other competing interests. Supplementary Files SMARTfRCTPFSSupplementaryTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 28 Apr, 2026 Reviewers invited by journal 27 Apr, 2026 Editor assigned by journal 13 Nov, 2025 Submission checks completed at journal 13 Nov, 2025 First submitted to journal 11 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8086622","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":632552685,"identity":"b779af0d-225b-4fbb-b256-e2bc71140b69","order_by":0,"name":"Nima Golijani-Moghaddam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYJACZiBibGBgPnggAcjjg4oaEKGFLQGshY0ELTwGBxiI0WIudvjw64Iaa9n+aWc+HHi4w06OTbqB8cMPhsPGuLRYzk5Ls55xLN14xu3cDQcSzyQbs8kcYJbsYThshkuLwe0cM2MetsOJDWAtbUAkkcAgzcBw2Aa/ln+HE+ffznkA08L8m4AW48e8bYcTN9zOYYBpYQPZgsdhaWnMvH3pxhtvpxkA1QP9IpHYZtljkI7T+wa3kw9/5vlmLTvvdvLDhz/b7OT4JZIP3/hRYW3YgEsPMCIk0ASAcYQ/IhmYP+CVHgWjYBSMglEAAAdtW4NT8UjoAAAAAElFTkSuQmCC","orcid":"","institution":"University of Lincoln","correspondingAuthor":true,"prefix":"","firstName":"Nima","middleName":"","lastName":"Golijani-Moghaddam","suffix":""},{"id":632552686,"identity":"8bf455b8-49fb-4417-b413-ba0be18b5b84","order_by":1,"name":"David L. 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The authors declare that they have no other competing interests.","formattedTitle":"Feasibility and acceptability of Strengthening Mental Abilities with Relational Training (SMART) for cognitive difficulties in multiple sclerosis: a randomised controlled trial","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pilot-and-feasibility-studies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pafs","sideBox":"Learn more about [Pilot and Feasibility Studies](http://pilotfeasibilitystudies.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/PAFS/default.aspx","title":"Pilot and Feasibility Studies","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Multiple Sclerosis, Cognitive Rehabilitation, Feasibility Randomised Controlled Trial, Relational Training","lastPublishedDoi":"10.21203/rs.3.rs-8086622/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8086622/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCognitive difficulties are common in multiple sclerosis (MS) and are associated with poorer quality of life, reduced independence, and lower employment. Despite growing interest in cognitive rehabilitation, existing interventions often lack generalisability and accessibility. Strengthening Mental Abilities with Relational Training (SMART) is a digital intervention targeting relational skills, which are theorised to underpin broader cognitive functioning. This trial evaluated the feasibility, acceptability, and preliminary signals of efficacy of SMART for people with MS experiencing cognitive difficulties.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted a three-arm parallel-group feasibility randomised controlled trial. Participants with a diagnosis of MS and self-reported cognitive problems were recruited from three NHS sites and randomised (1:1:1) to SMART plus treatment-as-usual (TAU), Active control (Sudoku) plus TAU, or TAU alone. Primary feasibility outcomes included recruitment, retention, intervention adherence, and data completeness. Acceptability was assessed using intervention-usage data and participant feedback. Candidate outcome measures included the Perceived Deficits Questionnaire (PDQ), Symbol Digit Modalities Test (SDMT), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), EQ-5D-5L, and ICECAP-A. Assessments took place at baseline, 3 months, and 6 months. The study was co-developed with people living with MS and their families through embedded patient and public involvement and engagement processes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eA total of 43 participants were randomised (72% of target). Retention was 84% at 3-month follow-up and 77% at 6 months. SMART adherence was high, with 93% of participants meeting the predefined criterion for training adherence. Acceptability feedback was consistently positive across arms. Data completeness for self-report and performance outcomes was acceptable (typically 60–80% across measures), though return rates for RBANS were lower due to postal logistics. Exploratory analysis suggested a moderate effect of SMART on perceived cognitive difficulties (PDQ, Cohen’s \u003cem\u003ed\u003c/em\u003e = 0.85 vs Active control; 0.69 vs TAU), with confidence intervals supporting the possibility of a clinically meaningful benefit. No clear between-group signal was observed on the SDMT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eTrial procedures were feasible, and the SMART intervention was acceptable to people with MS. 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