Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
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DOI：
10.1007/s00125-010-1988-1
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发表时间：
2011-03-01
期刊：
影响因子：
8.2
通讯作者：
Casas, R.
中科院分区：
文献类型：
--
作者：
Ludvigsson, J.;Hjorth, M.;Casas, R.
本研究的目的是调查明矾配制的谷氨酸脱羧酶GAD（65）（GAD-alum）治疗儿童和青少年1型糖尿病的安全性和有效性，随访4年后，70名10-18岁的儿童和青少年近期发作的1型糖尿病患者参加了一项II期、双盲、随机、安慰剂对照的临床试验。被确定为可能参与者的患者参加了瑞典八家诊所之一，以获得有关研究的信息并进行资格检查，包括病史。参与者被随机分配到两个治疗组中的一个，并在基线和1个月后接受皮下注射20 μ g GAD-alum或安慰剂。该研究对参与者和研究者设盲，直至第30个月。该研究在15个月时向申办者和统计学家揭盲，以评估数据。在30个月后的随访中，与安慰剂组相比，接受GAD明矾的组中残余胰岛素分泌（通过C肽测量）得到显著保留。这在基线病程< 6个月的患者中尤其明显。没有治疗相关的严重不良事件。我们已经对这些患者进行了4年的随访。总体而言，59名患者，29名接受GAD明矾治疗，30名接受安慰剂治疗，给予了知情同意书。每个治疗组中有一名患者在30至48个月期间发生了酮症酸中毒。未发生治疗相关不良事件。主要有效性终点是根据方案集，所有受试者的空腹C肽浓度从基线至预充注射后15个月的变化。在GAD明矾组中，空腹C肽在第1天为0.332 +/- 0.032 nmol/l，在第15个月为0.215 +/- 0.031 nmol/l。安慰剂组的相应数值分别为0.354 +/- 0.039和0.184 +/- 0.033 nmol/l。第1天和第1个月之间空腹C肽水平的下降在GAD明矾组中小于安慰剂组。治疗组之间的差异无统计学显著性。在那些在糖尿病诊断后6个月内接受治疗的患者中，4年后GAD-alum组的空腹C肽下降幅度显著低于安慰剂治疗组。GAD-alum治疗4年后，近期发病的1型糖尿病儿童和青少年继续显示无不良事件，并可能显示临床相关的保护C-peptide.ClinicalTrials.gov NCT 00435981该研究由瑞典研究理事会K 2008 - 55 X-20652-01-3、Barndiabetesfonden（瑞典儿童糖尿病基金会）、瑞典东南部研究理事会和Diamyd Medical AB的无限制资助。
The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up.Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with < 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent.One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years.Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide.ClinicalTrials.gov NCT00435981The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.