{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:39:45Z","timestamp":1781199585602,"version":"3.54.1"},"reference-count":59,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"unspecified","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006924","name":"International OCD Foundation","doi-asserted-by":"publisher","award":["Young Investigator's Award 2019"],"award-info":[{"award-number":["Young Investigator's Award 2019"]}],"id":[{"id":"10.13039\/100006924","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Cyclooxygenase (COX) enzymes oxidise arachidonic acid to prostaglandins, which modulate neuronal function and inflammation in the central nervous system. Consensus guidelines suggest non-steroidal anti-inflammatory drugs as a possible adjunctive approach in adults with obsessive\u2013compulsive disorder (OCD) and in children with acute-onset OCD subtypes. However, there is limited evidence to support this approach. The primary objective of this study is to determine the efficacy of the COX-2-selective inhibitor celecoxib as an adjunct to treatment-as-usual in children and youth with moderate-to-severe OCD. The safety of this intervention including adverse events will also be systematically assessed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>The<jats:underline>A<\/jats:underline>djunctive<jats:underline>CE<\/jats:underline>lecoxib in childhood-onset<jats:underline>OCD<\/jats:underline>(ACE-OCD) study is a single-centre randomised, quadruple-blind, placebo-controlled superiority trial with two parallel groups: celecoxib 100\u2009mg twice daily and placebo. Treatments will be added to participants\u2019 routine clinical care, which will not change over the course of the study. Target recruitment is 80 participants ages 7\u201318 with no recent treatment changes. The primary outcome is OCD severity after 12 weeks of treatment, measured by clinician-administered Children\u2019s Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Secondary outcomes include CY-BOCS score after 6 weeks; difference in the proportion of participants achieving a clinically meaningful response or remission; mean clinical global impression of severity and improvement after 6 and 12 weeks; and proportion of participants reporting adverse events possibly or probably related to the study intervention. The primary analyses, carried out according to intention-to-treat principles, will compare the celecoxib to placebo group on each outcome of interest, adjusting for baseline scores using analysis of covariance or logistic regression. Participants will be offered a 12-week open-label celecoxib extension and will be invited to participate in an ancillary study for biomarker analyses.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Ethics and dissemination<\/jats:title>\n<jats:p>This protocol has been approved by the University of British Columbia Children\u2019s and Women\u2019s Research Ethics Board and has received a No Objection Letter from Health Canada. The findings will be disseminated in peer-reviewed journals and presentations to multiple stakeholders including patients, parents and healthcare providers.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Trial registration number<\/jats:title>\n<jats:p>\n<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04673578\">NCT04673578<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/bmjopen-2021-054296","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T12:26:40Z","timestamp":1669724800000},"page":"e054296","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Celecoxib versus placebo as an adjunct to treatment-as-usual in children and youth with obsessive\u2013compulsive disorder: protocol for a single-site randomised quadruple-blind phase II study"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04673578","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04015596","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-3912","authenticated-orcid":false,"given":"Clara","family":"Westwell-Roper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5775-7053","authenticated-orcid":false,"given":"John R","family":"Best","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8712-8960","authenticated-orcid":false,"given":"Dean","family":"Elbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"MacFadden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4627-9030","authenticated-orcid":false,"given":"Susan","family":"Baer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-6759","authenticated-orcid":false,"given":"Lori","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Au","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Naqqash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyee","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0994-6383","authenticated-orcid":false,"given":"S Evelyn","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"2022112903181388000_12.1.e054296.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)07495-8"},{"key":"2022112903181388000_12.1.e054296.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2016.02.006"},{"key":"2022112903181388000_12.1.e054296.3","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30149"},{"key":"2022112903181388000_12.1.e054296.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.2004.00382.x"},{"key":"2022112903181388000_12.1.e054296.5","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1176\/ajp.155.2.264","article-title":"Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases","volume":"155","author":"Swedo","year":"1998","journal-title":"Am J Psychiatry"},{"key":"2022112903181388000_12.1.e054296.6","doi-asserted-by":"publisher","DOI":"10.1089\/cap.2014.0084"},{"key":"2022112903181388000_12.1.e054296.7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1001\/jamapsychiatry.2018.3428","article-title":"A nationwide study in Denmark of the association between treated infections and the subsequent risk of treated mental disorders in children and adolescents","volume":"76","author":"K\u00f6hler-Forsberg","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"2022112903181388000_12.1.e054296.8","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1001\/jamapsychiatry.2017.0995","article-title":"Association of streptococcal throat infection with mental disorders: testing key aspects of the PANDAS hypothesis in a nationwide study","volume":"74","author":"Orlovska","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"2022112903181388000_12.1.e054296.9","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v65n0303"},{"key":"2022112903181388000_12.1.e054296.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.02.021"},{"key":"2022112903181388000_12.1.e054296.11","doi-asserted-by":"crossref","unstructured":"Mataix-Cols D , Frans E , Perez-Vigil A . A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette\u2019s\/chronic tic disorders. Mol Psychiatry 2017.","DOI":"10.1038\/mp.2017.215"},{"key":"2022112903181388000_12.1.e054296.12","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1089\/cap.2018.0140","article-title":"Immune-related comorbidities in childhood-onset obsessive compulsive disorder: lifetime prevalence in the obsessive compulsive disorder collaborative genetics association study","volume":"29","author":"Westwell-Roper","year":"2019","journal-title":"J Child Adolesc Psychopharmacol"},{"key":"2022112903181388000_12.1.e054296.13","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1001\/jamapsychiatry.2017.1567","article-title":"Inflammation in the neurocircuitry of obsessive-compulsive disorder","volume":"74","author":"Attwells","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"2022112903181388000_12.1.e054296.14","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784480144"},{"key":"2022112903181388000_12.1.e054296.15","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.87.6.2851"},{"key":"2022112903181388000_12.1.e054296.16","doi-asserted-by":"publisher","DOI":"10.1002\/hup.2401"},{"key":"2022112903181388000_12.1.e054296.17","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3094642"},{"key":"2022112903181388000_12.1.e054296.18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jpsychires.2017.04.004","article-title":"Adjunctive celecoxib for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials","volume":"92","author":"Zheng","year":"2017","journal-title":"J Psychiatr Res"},{"key":"2022112903181388000_12.1.e054296.19","doi-asserted-by":"crossref","first-page":"605","DOI":"10.3389\/fpsyt.2019.00605","article-title":"Neurobiology and therapeutic potential of cyclooxygenase-2 (COX-2) inhibitors for inflammation in neuropsychiatric disorders","volume":"10","author":"Sethi","year":"2019","journal-title":"Front Psychiatry"},{"key":"2022112903181388000_12.1.e054296.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-012-2796-8"},{"key":"2022112903181388000_12.1.e054296.21","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1089\/cap.2016.0145","article-title":"Clinical management of pediatric acute-onset neuropsychiatric syndrome: part I-Psychiatric and behavioral interventions","volume":"27","author":"Thienemann","year":"2017","journal-title":"J Child Adolesc Psychopharmacol"},{"key":"2022112903181388000_12.1.e054296.22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neubiorev.2018.01.001","article-title":"Treatment of PANDAS and PANS: a systematic review","volume":"86","author":"Sigra","year":"2018","journal-title":"Neurosci Biobehav Rev"},{"key":"2022112903181388000_12.1.e054296.23","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.psychres.2011.01.019","article-title":"A preliminary randomized double-blind clinical trial on the efficacy of celecoxib as an adjunct in the treatment of obsessive-compulsive disorder","volume":"189","author":"Sayyah","year":"2011","journal-title":"Psychiatry Res"},{"key":"2022112903181388000_12.1.e054296.24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1055\/s-0035-1549929","article-title":"Celecoxib as an adjuvant to fluvoxamine in moderate to severe obsessive-compulsive disorder: a double-blind, placebo-controlled, randomized trial","volume":"48","author":"Shalbafan","year":"2015","journal-title":"Pharmacopsychiatry"},{"key":"2022112903181388000_12.1.e054296.25","doi-asserted-by":"crossref","first-page":"489","DOI":"10.32598\/bcn.2021.1998.1","article-title":"Effects of celecoxib adjunct to selective serotonin reuptake inhibitors on obsessive-compulsive disorder","volume":"12","author":"Shahini","year":"2021","journal-title":"BCN"},{"key":"2022112903181388000_12.1.e054296.26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-14-S1-S1"},{"key":"2022112903181388000_12.1.e054296.27","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e7586"},{"key":"2022112903181388000_12.1.e054296.28","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011412184"},{"key":"2022112903181388000_12.1.e054296.29","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.09m05305whi"},{"key":"2022112903181388000_12.1.e054296.30","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1989.01810110048007"},{"key":"2022112903181388000_12.1.e054296.31","first-page":"28","article-title":"The clinical global impressions scale: applying a research tool in clinical practice","volume":"4","author":"Busner","year":"2007","journal-title":"Psychiatry"},{"key":"2022112903181388000_12.1.e054296.32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2155-6180.1000334","article-title":"Methods for analysis of pre-post data in clinical research: a comparison of five common methods","volume":"8","author":"O'Connell","year":"2017","journal-title":"J Biom Biostat"},{"key":"2022112903181388000_12.1.e054296.33","doi-asserted-by":"publisher","DOI":"10.1002\/da.22389"},{"key":"2022112903181388000_12.1.e054296.34","first-page":"708","article-title":"Defining treatment response and remission in obsessive-compulsive disorder: a signal detection analysis of the children's Yale-Brown obsessive compulsive scale","volume":"49","author":"Storch","year":"2010","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2022112903181388000_12.1.e054296.35","doi-asserted-by":"crossref","DOI":"10.4137\/JCNSD.S38359","article-title":"Evidence-Based assessment of obsessive-compulsive disorder","volume":"8","author":"Rapp","year":"2016","journal-title":"J Cent Nerv Syst Dis"},{"key":"2022112903181388000_12.1.e054296.36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jaac.2018.05.029","article-title":"Development and psychometric evaluation of the children's yale-brown obsessive-compulsive scale second edition","volume":"58","author":"Storch","year":"2019","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2022112903181388000_12.1.e054296.37","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.psychres.2010.06.021","article-title":"A video clinical global impression (CGI) in obsessive compulsive disorder","volume":"186","author":"Bourredjem","year":"2011","journal-title":"Psychiatry Res"},{"key":"2022112903181388000_12.1.e054296.38","doi-asserted-by":"publisher","DOI":"10.1089\/cap.2014.0062"},{"key":"2022112903181388000_12.1.e054296.39","doi-asserted-by":"publisher","DOI":"10.1097\/01.chi.0000142668.29191.13"},{"key":"2022112903181388000_12.1.e054296.40","doi-asserted-by":"crossref","unstructured":"Buuren Svan , Groothuis-Oudshoorn K . mice: Multivariate Imputation by Chained Equations in R. J Stat Softw 2011;45:1. doi:10.18637\/jss.v045.i03","DOI":"10.18637\/jss.v045.i03"},{"key":"2022112903181388000_12.1.e054296.41","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/86.4.948"},{"key":"2022112903181388000_12.1.e054296.42","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2010.486301"},{"key":"2022112903181388000_12.1.e054296.43","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.4103\/1673-5374.165219","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and neuroprotection in the elderly: a view from the mitochondria","volume":"10","author":"Calvo-Rodr\u00edguez","year":"2015","journal-title":"Neural Regen Res"},{"key":"2022112903181388000_12.1.e054296.44","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445222"},{"key":"2022112903181388000_12.1.e054296.45","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.217372"},{"key":"2022112903181388000_12.1.e054296.46","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000287"},{"key":"2022112903181388000_12.1.e054296.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2012.06.003"},{"key":"2022112903181388000_12.1.e054296.48","doi-asserted-by":"publisher","DOI":"10.1097\/JGP.0b013e318227f4da"},{"key":"2022112903181388000_12.1.e054296.49","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.09m05117yel"},{"key":"2022112903181388000_12.1.e054296.50","doi-asserted-by":"publisher","DOI":"10.2146\/news070001"},{"key":"2022112903181388000_12.1.e054296.51","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080073"},{"key":"2022112903181388000_12.1.e054296.52","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1546-0096-12-29","article-title":"Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry","volume":"12","author":"Sobel","year":"2014","journal-title":"Pediatr Rheumatol Online J"},{"key":"2022112903181388000_12.1.e054296.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2005.01.004"},{"key":"2022112903181388000_12.1.e054296.54","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-013-0581-8"},{"key":"2022112903181388000_12.1.e054296.55","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jpain.2020.04.001","article-title":"Development and psychometric evaluation of the PROMIS pediatric pain intensity measure in children and adolescents with chronic pain","volume":"22","author":"Mara","year":"2021","journal-title":"J Pain"},{"key":"2022112903181388000_12.1.e054296.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.brat.2011.06.001"},{"key":"2022112903181388000_12.1.e054296.57","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.psychres.2015.03.034","article-title":"Contemporary models of pediatric obsessive-compulsive disorder: an evaluation with a large clinical sample","volume":"229","author":"De Nadai","year":"2015","journal-title":"Psychiatry Res"},{"key":"2022112903181388000_12.1.e054296.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.beth.2009.02.001"},{"key":"2022112903181388000_12.1.e054296.59","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-016-1616-6","article-title":"Assessment of clinical trial participant patient satisfaction: a call to action","volume":"17","author":"Pflugeisen","year":"2016","journal-title":"Trials"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-054296","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T12:27:08Z","timestamp":1669724828000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-054296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,31]]},"published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1136\/bmjopen-2021-054296"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-054296","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]}}}