دورية أكاديمية
Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials.
| العنوان: | Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials. |
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| المؤلفون: | Jacobsen LM; Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL., Cuthbertson D; Health Informatics Institute, University of South Florida, Tampa, FL., Bundy BN; Health Informatics Institute, University of South Florida, Tampa, FL., Atkinson MA; Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL., Moore W; Pediatric Endocrinology, Children's Mercy Hospital/University of Missouri-Kansas City Mercy, Kansas City, MO., Haller MJ; Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL., Russell WE; Vanderbilt University Medical Center, Nashville, TN., Gitelman SE; University of California San Francisco, San Francisco, CA., Herold KC; Yale University School of Medicine, New Haven, CT., Redondo MJ; Baylor College of Medicine, Texas Children's Hospital, Houston, TX., Sims EK; Department of Pediatrics, Indiana University, Indianapolis, IN., Wherrett DK; Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada., Moran A; Department of Pediatrics, University of Minnesota, Minneapolis, MN., Pugliese A; Department of Diabetes Immunology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope, Duarte, CA., Gottlieb PA; Barbara Davis Center, University of Colorado School of Medicine, Aurora, CO., Sosenko JM; Division of Endocrinology, University of Miami, Miami, FL., Ismail HM; Baylor College of Medicine, Texas Children's Hospital, Houston, TX. |
| مؤلفون مشاركون: | Type 1 Diabetes TrialNet Study Group |
| المصدر: | Diabetes care [Diabetes Care] 2024 Jun 01; Vol. 47 (6), pp. 1048-1055. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 7805975 Publication Model: Print Cited Medium: Internet ISSN: 1935-5548 (Electronic) Linking ISSN: 01495992 NLM ISO Abbreviation: Diabetes Care Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria Va : American Diabetes Association Original Publication: New York, American Diabetes Assn. |
| مواضيع طبية MeSH: | Diabetes Mellitus, Type 1*/therapy , Diabetes Mellitus, Type 1*/drug therapy , Diabetes Mellitus, Type 1*/immunology , C-Peptide*/blood , C-Peptide*/metabolism , Immunotherapy*/methods, Humans ; Female ; Male ; Adolescent ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Child ; Adult ; Area Under Curve |
| مستخلص: | Objective: Mixed-meal tolerance test-stimulated area under the curve (AUC) C-peptide at 12-24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy. Research Design and Methods: We examined data from six Type 1 Diabetes TrialNet immunotherapy randomized controlled trials in a post hoc analysis and included additional stimulated metabolic indices beyond C-peptide AUC. We partitioned the analysis into successful and unsuccessful trials and analyzed the data both in the aggregate as well as individually for each trial. Results: Among trials meeting their primary end point, we identified a treatment effect at 3 and 6 months when using C-peptide AUC (P = 0.030 and P < 0.001, respectively) as a dynamic measure (i.e., change from baseline). Importantly, no such difference was seen in the unsuccessful trials. The use of C-peptide AUC as a 6-month dynamic measure not only detected treatment efficacy but also suggested long-term C-peptide preservation (R2 for 12-month C-peptide AUC adjusted for age and baseline value was 0.80, P < 0.001), and this finding supported the concept of smaller trial sizes down to 54 participants. Conclusions: Early dynamic measures can identify a treatment effect among successful immune therapies in type 1 diabetes trials with good long-term prediction and practical sample size over a 6-month period. While external validation of these findings is required, strong rationale and data exist in support of shortening early-phase clinical trials. (© 2024 by the American Diabetes Association.) |
| References: | Diabetes Care. 2022 Feb 1;45(2):311-318. (PMID: 34853027) Diabetes Care. 2010 Mar;33(3):632-8. (PMID: 20028940) Diabetes. 2019 Jun;68(6):1267-1276. (PMID: 30967424) Lancet. 2011 Jul 23;378(9788):319-27. (PMID: 21714999) Diabetes Care. 2020 Aug;43(8):1836-1842. (PMID: 32457058) Ann N Y Acad Sci. 2008 Dec;1150:14-24. (PMID: 19120262) Lancet. 2013 Jun 1;381(9881):1905-15. (PMID: 23562090) Diabetes Care. 2010 Apr;33(4):826-32. (PMID: 20067954) Diabetes Care. 2018 Sep;41(9):1917-1925. (PMID: 30012675) Diabetes Care. 2020 Nov;43(11):2668-2674. (PMID: 32900788) Diabetes. 2021 Dec;70(12):2922-2931. (PMID: 34551936) Diabetes Care. 2014 Apr;37(4):979-84. (PMID: 24550217) Diabetes. 2020 Aug;69(8):1827-1832. (PMID: 32439823) Diabetes Care. 2015 Feb;38(2):271-6. (PMID: 25519451) Diabetes Care. 2018 Apr;41(4):653-661. (PMID: 29559451) Diabetes. 2021 Feb;70(2):638-651. (PMID: 33277338) Diabetes. 2004 Jan;53(1):250-64. (PMID: 14693724) J Clin Endocrinol Metab. 2023 May 17;108(6):1376-1386. (PMID: 36546354) Diabetes Care. 2008 Oct;31(10):1966-71. (PMID: 18628574) Diabetes Care. 2017 Nov;40(11):1494-1499. (PMID: 28860125) N Engl J Med. 2009 Nov 26;361(22):2143-52. (PMID: 19940299) Diabetologia. 2020 Mar;63(3):588-596. (PMID: 31768570) Diabetes Metab Res Rev. 2016 Nov;32(8):827-834. (PMID: 26991448) Diabetes Technol Ther. 2020 Dec;22(12):948-953. (PMID: 32833543) Clin Pharmacol Ther. 2023 Nov;114(5):972-980. (PMID: 37483175) Lancet. 2011 Jul 30;378(9789):412-9. (PMID: 21719096) |
| معلومات مُعتمدة: | P01 AI042288 United States AI NIAID NIH HHS; R01 DK121843 United States DK NIDDK NIH HHS; U01 DK106993 United States DK NIDDK NIH HHS; UC4 DK106993 United States DK NIDDK NIH HHS; UL1 TR001085 United States TR NCATS NIH HHS; U01 DK061042 United States DK NIDDK NIH HHS; UL1 TR002243 United States TR NCATS NIH HHS; U01 DK085476 United States DK NIDDK NIH HHS; M01 RR000400 United States RR NCRR NIH HHS; UL1 TR000445 United States TR NCATS NIH HHS; UL1 RR024139 United States RR NCRR NIH HHS; U01 DK061010 United States DK NIDDK NIH HHS; UL1 RR025761 United States RR NCRR NIH HHS; U01 DK061040 United States DK NIDDK NIH HHS; UL1 RR024153 United States RR NCRR NIH HHS; UL1 RR029890 United States RR NCRR NIH HHS; UL1 TR001857 United States TR NCATS NIH HHS; UL1 RR031986 United States RR NCRR NIH HHS; National Institute of Allergy and Infectious Diseases; U01 DK085466 United States DK NIDDK NIH HHS; UL1 TR001872 United States TR NCATS NIH HHS; U01 DK103153 United States DK NIDDK NIH HHS; U01 DK061058 United States DK NIDDK NIH HHS; UL1 TR002529 United States TR NCATS NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS; U01 DK085453 United States DK NIDDK NIH HHS; UL1 RR025780 United States RR NCRR NIH HHS; UL1 TR000114 United States TR NCATS NIH HHS; U01 DK085499 United States DK NIDDK NIH HHS; UL1 RR024131 United States RR NCRR NIH HHS; U01 DK106984 United States DK NIDDK NIH HHS; U01 DK107013 United States DK NIDDK NIH HHS; U01 DK103266 United States DK NIDDK NIH HHS; Diabetes TrialNet Study Group; P30 DK097512 United States DK NIDDK NIH HHS; K23 DK129799 United States DK NIDDK NIH HHS; UL1 TR001427 United States TR NCATS NIH HHS; U01 DK103282 United States DK NIDDK NIH HHS; UL1 RR024982 United States RR NCRR NIH HHS; K08 DK128628 United States DK NIDDK NIH HHS; UL1 RR025744 United States RR NCRR NIH HHS; U01 DK107014 United States DK NIDDK NIH HHS; U01 DK106994 United States DK NIDDK NIH HHS; HHSN267200800019C United States DK NIDDK NIH HHS; U01 DK061034 United States DK NIDDK NIH HHS; UL1 TR001082 United States TR NCATS NIH HHS; U01 DK085461 United States DK NIDDK NIH HHS; U01 DK085509 United States DK NIDDK NIH HHS; UL1 RR024975 United States RR NCRR NIH HHS; U01 DK103180 United States DK NIDDK NIH HHS; U01 DK085465 United States DK NIDDK NIH HHS; U01 DK085504 United States DK NIDDK NIH HHS; UL1TR002243 United States JDRF; National Institutes of Health (NIH) |
| تواريخ الأحداث: | Date Created: 20240415 Date Completed: 20240520 Latest Revision: 20240830 |
| رمز التحديث: | 20240830 |
| مُعرف محوري في PubMed: | PMC11294635 |
| DOI: | 10.2337/dc24-0171 |
| PMID: | 38621411 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1935-5548 |
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| DOI: | 10.2337/dc24-0171 |