{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:21Z","timestamp":1786977561915,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp;amp; Exp Dental Res"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The effective control of dental plaque is crucial for oral health, given that pathogenic bacteria in plaque are the primary cause of dental caries. Current antimicrobial agents, although effective, disrupt the oral microbiome and lead to oral dysbiosis, hindering efforts to curb dental caries. Novel antimicrobial peptides offer a promising solution due to their selective bactericidal activity against cariogenic bacteria. This study explores the initial safety and efficacy of KSL\u2010W formulated into chewing gum through a Phase 1 and 2a clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The combined trial, approved by the FDA, follows a double\u2010blind, randomized, placebo\u2010controlled design. Phase 1 assessed safety with single doses (2\u2212100\u2009mg), whereas Phase 2a explored both safety and proof of concept in reducing oral bacteria with multiple doses (4\u221275\u2009mg). Besides adverse events (Phase 1), outcome measures included whole\u2010mouth plaque and gingival index scores and bleeding on probing (Phase 2a).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>KSL\u2010W demonstrated safety in both phases, with no severe adverse events. The proof\u2010of\u2010concept analysis revealed a decrease in plaque and gingival inflammation, particularly at doses \u2265\u200920\u2009mg. The 30\u2009mg dose appeared to yield optimal effects without any adverse reactions in subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Results from this study indicate that KSL\u2010W is safe for use in humans and provides initial evidence of its potential efficacy in reducing plaque and gingival inflammation. Further research is essential to determine optimal usage and ultimate safety, and to assess its potential in diverse populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      The trial is registered with the FDA (Trial Registration Number: NCT01877421). The clinical trials were registered in the\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                      database under the title \u201cSafety and Tolerability of Antiplaque Chewing Gum in a Gingivitis Population\u201d and the identifier number is NCT01877421. The URL for accessing the study in clinicaltrials.gov is\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT01877421?intr=Antiplaque%20chewing%26rank=1\">https:\/\/clinicaltrials.gov\/study\/NCT01877421?intr=Antiplaque%20chewing&amp;rank=1<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cre2.943","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T14:13:33Z","timestamp":1730124813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Combined Phase 1\/2a Initial Clinical Safety Trials and Proof\u2010of\u2010Concept Assessment of a Novel Antimicrobial Peptide KSL\u2010W Anti\u2010Plaque Chewing Gum"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-8648","authenticated-orcid":false,"given":"J. Brett","family":"Ryan","sequence":"first","affiliation":[{"name":"US Air Force Dental Research and Consultation Service  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"Clinical Technology Integration US Army Institute of Surgical Research  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai P.","family":"Leung","sequence":"additional","affiliation":[{"name":"Combat Wound Care Group US Army Institute of Surgical Research San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"issue":"4","key":"e_1_2_12_2_1","first-page":"229","article-title":"Problems and Proposals for Recording Gingivitis and Plaque","volume":"25","author":"Ainamo J.","year":"1975","journal-title":"International Dental Journal"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-016-0706-9"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1377\/hpb20230921.68748"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1208\/pt0801026"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fdmed.2022.995423"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00302"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2019.00043"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-5037.2008.00344.x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cden.2017.12.001"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00319"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0895937409335627"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15092278"},{"issue":"1","key":"e_1_2_12_14_1","first-page":"3","article-title":"A Modified Gingival Index for Use in Clinical Trials","volume":"8","author":"Lobene R. 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