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Beta-cell protective or beta-cell regenerative approaches have gained wider attention, and pharmacological approaches to protect the patient\u2019s own insulin-producing beta-cell mass have been proposed. Verapamil is an L-type calcium channel blocker that has been reported to effectively lowers beta-cell thioredoxin-interacting protein expression in rodent beta cells and islets, as well as in human islets, and thus promotes functional beta-cell mass.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The trial is a multicentre, randomised, double-blind, placebo-controlled trial in participants with T1DM, investigating the effect of verapamil on preservation of beta-cell function (Ver-A-T1D). A total of 120 participants will be randomised in a 2:1 ratio between 360\u2009mg verapamil and placebo, administered orally once daily. T1DM patients aged \u226518\u2009and &lt;45 years will be eligible for recruitment within 6 weeks of diagnosis (defined as day of starting insulin therapy). The primary objective will be to determine the changes in stimulated C-peptide response during the first 2\u2009hours of a mixed meal tolerance test at baseline and after 12 months for 360\u2009mg verapamil administered orally once daily versus placebo. Secondary objectives include the effects of 360\u2009mg verapamil on (1) fasting C-peptide, (2) dried blood spot C-peptide, (3) glycated haemoglobin, (4) daily total insulin dose, (5) time in range by intermittent continuous glucose monitoring measures, (6) other biomarkers related to immunological changes and beta-cell death and (6) safety (vital signs, ECG).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>\n                      Ethics approval was sought from the research ethics committee of all participating countries. All participants provided written informed consent before joining the study. Ver-A-T1D received first regulatory and ethical approvals in Austria. The publication policy is set in the innovative approach towards understanding and arresting type 1 diabetes grant agreement (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"www.innodia.eu\">www.innodia.eu<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      EudraCT, 2020-000435-45; ClinicalTrials.gov,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04545151\">NCT04545151<\/jats:ext-link>\n                      . Protocol version: Version 8.0 (08 November 2021).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-091597","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T02:07:13Z","timestamp":1732846033000},"page":"e091597","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Investigating the effect of verapamil on preservation of beta-cell function in adults with newly diagnosed type 1 diabetes mellitus (Ver-A-T1D): protocol for a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04545151","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0111-083X","authenticated-orcid":false,"given":"Julie","family":"Wych","sequence":"first","affiliation":[{"name":"Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1389-8857","authenticated-orcid":false,"given":"Martina","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Stenson","sequence":"additional","affiliation":[{"name":"Diabetes Research Group, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr Jaroslaw","family":"Chmura","sequence":"additional","affiliation":[{"name":"Center for Protein Research, Kobenhavns Universitet Sundhedsvidenskabelige Fakultet, Kobenhavn, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Danne","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics Endocrinology\/Diabetology & Clinical Research, Auf der Bult Children's Hospital, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Paul","family":"Mander","sequence":"additional","affiliation":[{"name":"Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit Leuven, UZ Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Dayan","sequence":"additional","affiliation":[{"name":"Cardiff University School of Medicine, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R","family":"Pieber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"2025121223570100000_14.11.e091597.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31320-5"},{"key":"2025121223570100000_14.11.e091597.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"2025121223570100000_14.11.e091597.3","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0418"},{"key":"2025121223570100000_14.11.e091597.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199309303291401"},{"key":"2025121223570100000_14.11.e091597.5","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0881"},{"key":"2025121223570100000_14.11.e091597.6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/bmb\/ldab027","article-title":"Immunotherapy for type 1 diabetes","volume":"140","author":"Allen","year":"2021","journal-title":"Br Med Bull"},{"key":"2025121223570100000_14.11.e091597.7","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1831"},{"key":"2025121223570100000_14.11.e091597.8","doi-asserted-by":"crossref","first-page":"174061","DOI":"10.1016\/j.ejphar.2021.174061","article-title":"Inhibition of thioredoxin-interacting protein and inflammasome assembly using verapamil mitigates diabetic retinopathy and pancreatic injury","volume":"901","author":"Eissa","year":"2021","journal-title":"Eur J Pharmacol"},{"key":"2025121223570100000_14.11.e091597.9","doi-asserted-by":"crossref","unstructured":"Domingues A , Jolibois J , Roug\u00e9 P , et al . 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