Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

作者：Stephen E. Gitelman, Brian N. Bundy, Ele Ferrannini, Noha Lim, Lori Blanchfield, Linda A. DiMeglio, Eric I. Felner, Jason L. Gaglia, Peter A. Gottlieb, S. Alice Long, Andrea Mari, Raghavendra G. Mirmira, Philip Raskin, Srinath Sanda, Eva Tsalikian, John M. Wentworth, Steven M. Willi, Jeffrey P. Krischer, Jeffrey A. Bluestone, Mayalin Barr, Lori Blanchfield, Jeffrey A. Bluestone, Jeanne Buchanan, Brian N. Bundy, Joanne Cabbage, Peter G. Coleman, Monica De La Vega, Linda A. DiMeglio, Carmella Evans‐Molina, Eric I. Felner, Ele Ferrannini, Christine Ferrara, Jason L. Gaglia, Stephen E. Gitelman, Peter A. Gottlieb, Felicity Healy, Laurie Higgins, Megan Hildinger, Margaret A. Jenkins, Nora Bryant, Amanda Kinderman, Nisha Koshy, Brianne Kost, Jeffrey P. Krischer, Suzanne Krishfield, Olena Kucheruk, Noha Lim, Karen L. Lindsley, S. Alice Long, Manasa Mantravadi, Andrea Mari, Shelley Mesfin, Aaron W. Michels, Mary Ellen Migre, Pantea Minnock, Raghavendra G. Mirmira, Elham Mohammed-Nur, Jennifer B. Nelson, Ashvin Nursing, Ryan O’Donnell, Diana R. Olivos, Melissa M. Parker, Philip Raskin, Leanne Redl, Nicole Reed, Brittany Resnick, Srinath Sanda, Peter H. Sayre, Elisavet Serti, Emily Sims, Karen Smith, Carol L. Soppe, Fiona Stuart, Sarah Szubowicz, Michel Tansey, Jennifer Terrell, Sarah A. Tersey, Christine Torok, Eva Tsalikian, Kelly Watson, John M. Wentworth, Rebecca Wesch, Steven M. Willi, Stéphanie Woerner · 发表于：The Lancet Diabetes & Endocrinology · 年份：2021 · DOI：10.1016/s2213-8587(21)00139-x · 被引用次数：135 · 研究领域：Chronic Myeloid Leukemia Treatments、Diabetes and associated disorders、Diabetes Management and Research

BACKGROUND: Type 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes. METHODS: on a mixed meal tolerance test (MMTT) were enrolled from nine medical centres in the USA (n=8) and Australia (n=1). Participants were randomly assigned (2:1) to receive either 400 mg imatinib mesylate (4 × 100 mg film-coated tablets per day) or matching placebo for 26 weeks via a computer-generated blocked randomisation scheme stratified by centre. Treatment assignments were masked for all participants and study personnel except pharmacists at each clinical site. The primary endpoint was the difference in the area under the curve (AUC) mean for C-peptide response in the first 2 h of an MMTT at 12 months in the imatinib group versus the placebo group, with use of an ANCOVA model adjusting for sex, baseline age, and baseline C-peptide, with further observation up to 24 months. The primary analysis was by intention to treat (ITT). Safety was assessed in all randomly assigned participants. This study is registered with ClinicalTrials.gov, NCT01781975 (completed). FINDINGS: Patients were screened and enrolled between Feb 12, 2014, and May 19, 2016. 45 patients were assigned to receive imat...