Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Austria.
Trials. 2010 Oct 6;11:91. doi: 10.1186/1745-6215-11-91.
New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.
METHODS/DESIGN: This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.
NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.
ClinicalTrials.gov NCT00980356.
新诊断的移植后糖尿病（NODAT）是移植后一种常见且严重的并发症，与移植物和患者存活率降低有关。目前，它主要根据现有的 2 型糖尿病指南进行诊断和治疗。迄今为止，只有少数试验研究了 NODAT 患者的抗糖尿病药物。维格列汀是一种新型的二肽基肽酶-4（DPP-4）抑制剂，通过增强对血糖升高的α-和β-细胞的反应性来改善胰岛功能。实验数据表明 DPP-4 抑制剂对包括免疫抑制剂在内的外源应激刺激后胰岛功能具有潜在的保护作用。因此，用这类化合物治疗 NODAT 似乎很有吸引力。目前，维格列汀作为单药或与其他抗糖尿病药物联合用于治疗 2 型糖尿病，因为它能有效降低糖化血红蛋白（HbA1c）值。此外，维格列汀在肾功能中度受损的患者中也被证明是安全的。本研究将评估维格列汀单药治疗近期诊断为 NODAT 的肾移植受者的安全性和疗效。
方法/设计：这是一项随机、安慰剂对照、双盲、前瞻性的 II 期临床试验。根据我们中心稳定肾移植患者常规进行的口服葡萄糖耐量试验（OGTT）结果，我们将招募无糖尿病病史且 2 小时血糖值超过 200mg/dl（11.1mmol/l）的患者。他们被随机分为每天服用 50mg 维格列汀或安慰剂。共有 32 名新诊断为 NODAT 的患者入选。主要终点是治疗开始后 3 个月重复 OGTT 时与基线相比的 2 小时血糖值的差异，比较维格列汀组和安慰剂组。次要终点包括 HbA1c 和空腹血浆葡萄糖（FPG）的变化。通过症状性低血糖发作（血糖<72mg/dl 或 4mmol/l）、不良事件和可能与药物相关的副作用的数量来评估维格列汀在肾移植患者中的安全性。
NODAT 是肾移植后的一种严重并发症。很少有试验评估这些患者的抗糖尿病药物的安全性和疗效。本研究的目的是评估维格列汀在 NODAT 肾移植患者中的安全性和疗效。
ClinicalTrials.gov NCT00980356。
