St Vincent's Institute of Medical Research, Melbourne, Australia.
Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, 3065, Australia.
Trials. 2022 May 23;23(1):433. doi: 10.1186/s13063-022-06356-z.
Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function.
This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses.
This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D.
ANZCTR ACTRN12620000239965 . Registered on 26 February 2020.
gov NCT04774224. Registered on 01 March 2021.
1 型糖尿病（T1D）给个人及其家庭以及医疗保健系统带来了巨大的负担。尽管葡萄糖传感器和胰岛素泵技术最近取得了进展，但只有少数患者能够达到血糖目标，面临急性和长期并发症的风险，其中一些并发症是危及生命的。JAK-STAT 途径对于 T1D 中的免疫介导的胰岛β细胞破坏至关重要。我们的临床前数据表明，JAK1/JAK2 抑制剂可预防糖尿病并逆转 T1D 非肥胖型糖尿病小鼠模型中的新发糖尿病。本研究的目的是确定 JAK1/JAK2 抑制剂巴瑞替尼是否会损害 1 型糖尿病自身免疫并保留β细胞功能。
这将是一项在发病后 10-30 岁的近期诊断为 T1D 的个体中进行的多中心、双臂、双盲、安慰剂对照随机试验。83 名参与者将在诊断后 100 天内按照 2:1 的比例随机分为巴瑞替尼 4mg/天组或安慰剂组，接受 48 周治疗，然后在停止研究药物后再监测 48 周。主要结局是摄入混合餐后的血浆 C 肽 2h 曲线下面积。次要结局包括 HbA1c、胰岛素剂量、连续血糖谱和不良事件。机制评估将描述一般和糖尿病特异性免疫反应。
本研究将确定巴瑞替尼是否能减缓 T1D 临床发病后发生的免疫介导的β细胞功能进行性丧失。β细胞功能的保留预计会改善血糖控制并预防糖尿病并发症，并证明巴瑞替尼联合其他疗法的进一步试验以及在高危人群中预防 T1D 的使用是合理的。
ANZCTR ACTRN12620000239965。于 2020 年 2 月 26 日注册。临床试验：gov NCT04774224。于 2021 年 3 月 1 日注册。
