Cabrera-Rode Eduardo, Cubas-Dueñas Ileana, Rodríguez-Acosta Janet, García-García Yudith, Torres-López Yelena, Prieto-Noa Claudia, Vázquez-Izada Bárbara M, Ruíz-Reinoso Maité, Echevarría-Valdés Ragmila, Álvarez-Álvarez Aimee, Domínguez-Alonso Emma, Conesa-González Ana Ibis, González-Calero Teresa, Robles-Torres Erick, Turcios-Tristá Silvia Elena, Senra-Estévez Elizabeth, Hernández-Casaña Patricia, Sarmiento Luis
Institute of Endocrinology, University of Medical Sciences of Havana, Zapata and D, Plaza, Havana 10400, Cuba.
Center of Molecular Immunology, 216 Street and 15 Avenue, Atabey, Playa, P.O. Box 16040, Havana 11600, Cuba.
J Clin Med. 2022 Mar 24;11(7):1789. doi: 10.3390/jcm11071789.
We conducted a phase I-IIa, randomized, monocentric, double-blind, placebo-controlled clinical trial to evaluate the safety and impact of the combination treatment of Itolizumab and insulin on preserving beta cell function in adults with recent-onset type 1 diabetes. Twelve patients were randomly assigned to three treatment groups, each receiving a different Itolizumab dose (0.4/0.8/1.6 mg/kg body weight, respectively) and a placebo group. All patients received concomitant intensive multiple-dose insulin therapy. Endogenous insulin secretion was assessed by the measurement of C-peptide during the mixed-meal tolerance test. No serious adverse events were reported. No changes in the total daily insulin doses, glycated hemoglobin levels, and stimulated C-peptide were observed between the Itolizumab and placebo groups at 52 weeks. A significant decrease in stimulated C-peptide was observed during the follow-up period ( = 0.012). One subject treated with 1.6 mg of Itolizumab showed a marked increase in the levels of stimulated C-peptide three years after completion of the trial. Taken together, this is the first study to demonstrate that combination treatment with Itolizumab and insulin is safe in humans and does not affect the residual function of beta cells up to 52 weeks. The findings from our study show preliminary evidence that high doses of Itolizumab could potentially arrest the loss of beta cell function in the long term. Further studies with a longer follow-up and larger numbers of patients are envisaged to assess the effect with high dose Itolizumab.
我们开展了一项I-IIa期、随机、单中心、双盲、安慰剂对照临床试验，以评估英夫利昔单抗与胰岛素联合治疗对近期发病的1型糖尿病成年患者β细胞功能的安全性和影响。12名患者被随机分配到三个治疗组，每组分别接受不同剂量的英夫利昔单抗（分别为0.4/0.8/1.6 mg/kg体重）和一个安慰剂组。所有患者均接受强化多次剂量胰岛素治疗。通过混合餐耐量试验期间测量C肽来评估内源性胰岛素分泌。未报告严重不良事件。在52周时，英夫利昔单抗组和安慰剂组之间的每日胰岛素总剂量、糖化血红蛋白水平和刺激后的C肽均未观察到变化。在随访期间观察到刺激后的C肽显著下降（P = 0.012）。一名接受1.6 mg英夫利昔单抗治疗的受试者在试验完成三年后，刺激后的C肽水平显著升高。综上所述，这是第一项证明英夫利昔单抗与胰岛素联合治疗对人类安全且在52周内不影响β细胞残余功能的研究。我们研究的结果显示了初步证据，即高剂量英夫利昔单抗可能长期阻止β细胞功能丧失。设想进行进一步的研究，随访时间更长且患者数量更多，以评估高剂量英夫利昔单抗的效果。
