{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:28:06Z","timestamp":1781144886050,"version":"3.54.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,12,13]],"date-time":"2015-12-13T00:00:00Z","timestamp":1449964800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We examined the efficacy and safety of ranirestat in patients with diabetic sensorimotor polyneuropathy (<jats:styled-content style=\"fixed-case\">DSPN<\/jats:styled-content>). Patients (18\u201375 years) with stable type 1\/2 diabetes mellitus and <jats:styled-content style=\"fixed-case\">DSPN<\/jats:styled-content> were eligible for this global, double\u2010blind, phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> study (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> NCT00927914). Patients (n\u2009=\u2009800) were randomized 1\u2009:\u20091\u2009:\u20091 to placebo, ranirestat 40\u2009mg\/day or 80\u2009mg\/day (265\u2009:\u2009264\u2009:\u2009271). Change in peroneal motor nerve conduction velocity (<jats:styled-content style=\"fixed-case\">PMNCV<\/jats:styled-content>) from baseline to 24 months was the primary endpoint with a goal improvement vs. placebo \u22651.2\u2009m\/s. Other endpoints included symptoms, quality\u2010of\u2010life, and safety. Six hundred thirty\u2010three patients completed the study. The <jats:styled-content style=\"fixed-case\">PMNCV<\/jats:styled-content> difference from placebo was significant at 6, 12, and 18 months in both ranirestat groups, but &lt;1.2\u2009m\/s. The mean improvement from baseline at 24 months was +0.49, +0.95, and +0.90\u2009m\/s for placebo, ranirestat 40\u2009mg and 80\u2009mg, respectively (<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>). The treatment difference vs. placebo reached significance when ranirestat groups were combined in a <jats:italic>post hoc<\/jats:italic> analysis (+0.44\u2009m\/s; p\u2009=\u20090.0237). There was no effect of ranirestat on safety assessments, secondary or exploratory endpoints vs. placebo. Ranirestat was well tolerated and improved <jats:styled-content style=\"fixed-case\">PMNCV<\/jats:styled-content>, but did not achieve any efficacy endpoints. The absence of <jats:styled-content style=\"fixed-case\">PMNCV<\/jats:styled-content> worsening in the placebo group underscores the challenges of <jats:styled-content style=\"fixed-case\">DSPN<\/jats:styled-content> studies in patients with well\u2010controlled diabetes.<\/jats:p>","DOI":"10.1111\/jns.12138","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T12:43:07Z","timestamp":1440679387000},"page":"363-371","source":"Crossref","is-referenced-by-count":26,"title":["Safety and efficacy of ranirestat in patients with mild\u2010to\u2010moderate diabetic sensorimotor polyneuropathy"],"prefix":"10.1111","volume":"20","author":[{"given":"Michael","family":"Polydefkis","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Arezzo","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience and Neurology Albert Einstein College of Medicine  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Nash","sequence":"additional","affiliation":[{"name":"NeuroStudies.net LLC  Decatur GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Bril","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Shaibani","sequence":"additional","affiliation":[{"name":"Nerve &amp; Muscle Center of Texas  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Eisai Ltd  Hatfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate L.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Eisai Ltd  Hatfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick W. J.","family":"Junor","sequence":"additional","affiliation":[{"name":"Eisai Ltd  Hatfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Ranirestat Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2005.08.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.10.2369"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.29.01.06.dc05-1447"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-2110"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.25.11.2010"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0919-2"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410380607"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1955.10501294"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2307\/2528490"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2337\/diacare.12.9.649","article-title":"Meaningful degrees of prevention or improvement of nerve conduction in controlled clinical trials of diabetic neuropathy","volume":"12","author":"Dyck PJ","year":"1989","journal-title":"Diabetes Care"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.49.1.229"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000149522.32823.EA"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns5.12021"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.15.12.1902"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)02478-7"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945008783431781"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/175901"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199507133330203"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh175"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.01.015"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-0608"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2008.11.004"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2008.03.011"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0503"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjns.12138","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjns.12138","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.12138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T13:41:32Z","timestamp":1696254092000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns.12138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1111\/jns.12138"],"URL":"https:\/\/doi.org\/10.1111\/jns.12138","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"value":"1085-9489","type":"print"},{"value":"1529-8027","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]}}}