{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T23:43:30Z","timestamp":1773445410385,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>Pain is underdiagnosed and often not adequately treated, contributing to behavioral and psychological symptoms of dementia (BPSD). BPSD are treated with atypical antipsychotics that are associated with severe cerebrocardiovascular effects. Interestingly, treatment of pain may reduce agitation. Research is focusing on nonpharmacological treatment, such as aromatherapy, for pain and BPSD in dementia. This clinical study will assess the effect on agitation in severely demented elderly of BEO loaded in a nanotechnological odorless cream indistinguishable from placebo. This is a protocol for a randomized, double\u2010blind, placebo\u2010controlled trial (NCT04321889). A total of 134 patients aged \u226565\u2009years with severe dementia (mini\u2010mental state examination &lt;12) will be recruited and randomly allocated 1:1 to either BEO or placebo group. After baseline screening, BEO (80\u2009mg) cream or placebo cream will be trans\u2010dermally applied on both arms twice a day for 4\u2009weeks with a 4\u2010week follow\u2010up period. The effect on agitation will be the primary endpoint. Any adverse events will be reported. A double\u2010blind, clinical trial evaluating efficacy and safety of an essential oil endowed with strong analgesic properties has never been carried out before. This study could form the basis for a safer and more effective treatment of BPSD in severe dementia.<\/jats:p>","DOI":"10.1002\/ptr.7223","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T08:13:38Z","timestamp":1629965618000},"page":"5333-5338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Bergamot rehabilitation <scp>AgaINst<\/scp> agitation in dementia (<scp>BRAINAID<\/scp>): Study protocol for a randomized, double\u2010blind, placebo\u2010controlled trial to assess the efficacy of furocoumarin\u2010free bergamot loaded in a nanotechnology\u2010based delivery system of the essential oil in the treatment of agitation in elderly affected by severe dementia"],"prefix":"10.1002","volume":"35","author":[{"given":"Damiana","family":"Scuteri","sequence":"first","affiliation":[{"name":"Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition University of Calabria  Rende Italy"},{"name":"S. Anna Institute, Regional Center for Serious Brain Injuries  Crotone Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Sandrini","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia, IRCCS C. Mondino Foundation Neurologic Institute  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Tamburin","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Tiziana","family":"Corasaniti","sequence":"additional","affiliation":[{"name":"Department of Health Science University \u201cMagna Graecia\u201d of Catanzaro  Catanzaro Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierluigi","family":"Nicotera","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Tonin","sequence":"additional","affiliation":[{"name":"S. Anna Institute, Regional Center for Serious Brain Injuries  Crotone Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-6218","authenticated-orcid":false,"given":"Giacinto","family":"Bagetta","sequence":"additional","affiliation":[{"name":"Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition University of Calabria  Rende Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"e_1_2_1_8_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S36739"},{"key":"e_1_2_1_8_3_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.v63n0703"},{"key":"e_1_2_1_8_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000324438"},{"key":"e_1_2_1_8_5_1","unstructured":"Farmacopea Ufficiale & Italiana. (1991).Droghe Vegetali e Preparazioni (IX Edizione)."},{"key":"e_1_2_1_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003150.pub2"},{"key":"e_1_2_1_8_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610219002011"},{"key":"e_1_2_1_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.593"},{"key":"e_1_2_1_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d4065"},{"key":"e_1_2_1_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2019.05.022"},{"key":"e_1_2_1_8_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/s1041610218000534"},{"key":"e_1_2_1_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1688"},{"key":"e_1_2_1_8_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/acm.2019.0222"},{"key":"e_1_2_1_8_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/21556660.2016.1278545"},{"key":"e_1_2_1_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2006.11.010"},{"key":"e_1_2_1_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-13-315"},{"key":"e_1_2_1_8_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14404"},{"key":"e_1_2_1_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2156873"},{"key":"e_1_2_1_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000095"},{"key":"e_1_2_1_8_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.15.1934"},{"key":"e_1_2_1_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13030379"},{"key":"e_1_2_1_8_22_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2019.55.11.3069864"},{"key":"e_1_2_1_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2018.06.007"},{"key":"e_1_2_1_8_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.237125"},{"key":"e_1_2_1_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.640128"},{"key":"e_1_2_1_8_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00890"},{"key":"e_1_2_1_8_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9416305"},{"key":"e_1_2_1_8_28_1","doi-asserted-by":"publisher","DOI":"10.11138\/fneur\/2017.32.4.229"},{"key":"e_1_2_1_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133327"},{"key":"e_1_2_1_8_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666180307115546"},{"key":"e_1_2_1_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-020-02995-w"},{"key":"e_1_2_1_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1993.tb01892.x"},{"key":"e_1_2_1_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051381"},{"key":"e_1_2_1_8_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/acm.2017.0320"},{"key":"e_1_2_1_8_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2018.2123"},{"key":"e_1_2_1_8_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01058"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7223","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.7223","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T23:52:48Z","timestamp":1692834768000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.7223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,26]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/ptr.7223"],"URL":"https:\/\/doi.org\/10.1002\/ptr.7223","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,26]]},"assertion":[{"value":"2021-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}