Osei Elizabeth, Fonville Susanne, Zandbergen Adrienne A M, Brouwers Paul J A M, Mulder Laus J M M, Lingsma Hester F, Dippel Diederik W J, Koudstaal Peter J, den Hertog Heleen M
Department of Neurology, Medisch Spectrum Twente, PO Box 50 000, Enschede, 7500, KA, The Netherlands.
Department of Neurology, Erasmus Medical Center University Hospital, Rotterdam, The Netherlands.
Trials. 2015 Aug 5;16:332. doi: 10.1186/s13063-015-0882-z.
Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients.
METHODS/DESIGN: The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months.
This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance.
NTR3196 , Date of registration: 15 December 2011.
三分之一的短暂性脑缺血发作（TIA）或缺血性卒中患者存在糖耐量受损，且复发性卒中风险增加两倍。二甲双胍可改善糖耐量，但常导致副作用。本研究旨在探讨二甲双胍和西他列汀用于TIA或轻度缺血性卒中且糖耐量受损患者的可行性、安全性及对糖代谢的影响。我们还将评估二甲双胍剂量缓慢增加以及对该治疗给予更好的支持和信息是否会降低这些患者的副作用发生率。
方法/设计：糖耐量受损合并近期TIA或轻度缺血性卒中患者的二甲双胍和西他列汀试验（MAAS试验）是一项II期、多中心、随机、对照、开放标签试验，结果评估采用盲法。纳入近期（<6个月）发生TIA、一过性黑矇或轻度缺血性卒中（改良Rankin量表评分≤3）且糖耐量受损的非糖尿病患者（n = 100），糖耐量受损定义为重复标准口服葡萄糖耐量试验后负荷后2小时血糖水平在7.8至11.0 mmol/L之间。排除有肾或肝功能损害、心力衰竭、慢性缺氧性肺病III - IV期、乳酸酸中毒或糖尿病酮症酸中毒病史、妊娠或哺乳期、胰腺炎以及正在使用地高辛的患者。患者将按1:1:2的比例随机分配至二甲双胍组、西他列汀组或“无治疗”组。分配至二甲双胍组的患者起始剂量为每日两次，每次500 mg，在6周内逐渐增加至每日两次，每次1000 mg。分配至西他列汀组的患者将接受每日固定剂量100 mg的治疗。该研究已在荷兰试验注册中心注册，注册号为NTR 3196。主要结局包括仍在接受治疗的百分比、（严重）不良事件的百分比以及6个月时负荷后2小时血糖水平的基线校正差异。
本研究将提供更多关于二甲双胍和西他列汀在TIA或缺血性卒中且糖耐量受损患者中的可行性、安全性以及对6个月时负荷后2小时血糖水平影响的信息。
NTR3196，注册日期：2011年12月15日。
