PERL: A multi-center clinical trial of allopurinol to prevent GFR loss in T1D

PERL:别嘌呤醇预防 T1D 患者 GFR 损失的多中心临床试验

基本信息

  • 批准号:
    9738022
  • 负责人:
  • 金额:
    $ 25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-09-30 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

SUMMARY Despite improvements in the past 20 years in glycemia and blood pressure (BP) control, and the introduction of “renoprotective” drugs such as renin-angiotensin system blockers (RASB), the overall incidence of end- stage renal disease (ESRD) in type 1 diabetes (T1D) is not declining. Novel therapies to complement these interventions are urgently needed. Convincing evidence from multiple cohort studies indicates that higher serum uric acid levels (SUA) predict a substantial increase in the risk of chronic kidney disease (CKD) and accelerated glomerular filtration rate (GFR) loss among persons with T1D. To study whether SUA lowering can reduce GFR loss in T1D, we established a unique consortium of investigators from 16 academic centers in the US, Canada, and Denmark. Led by co-PIs, Drs. Doria from the Joslin Kidney Study, and Mauer, formerly PI of the Renin Angiotensin System Study (RASS) clinical trial, the Consortium has been named PERL (Preventing Early Renal Function Loss in Diabetes) to emphasize its focus on intervening relatively early in the course of CKD in T1D, when renal damage is more likely to be arrestable or reversible and interventions are thus more likely to be effective. With the support of NIH grants R03 DK094484, R34 DK097808, UC4 DK101108, and a JDRF grant, the PERL Consortium is currently conducting a multi-center, double-blind, clinical trial in which 530 patients with T1D of ≥8 years of duration, mild to moderate decrease in GFR, moderately increased SUA (≥4.5 mg/dl), and a history of either elevated urinary excretion of albumin or accelerated GFR decline were randomized to receive the urate-lowering drug allopurinol (200 to 400 mg per day depending on renal function) or placebo for three years. The primary outcome is the GFR (as measured by iohexol plasma disappearance) at the end of a 2-month wash-out period after the 3-year intervention. PERL successfully completed randomization of the 530 participants (10% more than the initial recruitment goal) in May 2016, with the last participant visit planned for June 2019. PERL participant retention and adherence have been excellent. The purpose of this application is to renew NIH grant UC4 DK101108, which currently supports all aspects of the trial and is projected to cover costs until October 2017. Funding after that date will allow completion of the 3-year treatment period for all PERL subjects, this being necessary for adequate power to answer the trial's questions as delineated in the protocol approved by NIDDK and the DSMB. This grant renewal will also provide support for data analysis and manuscript writing upon trial completion. If PERL demonstrates that allopurinol can halt or slow the rate of GFR decline in persons with T1D, it would provide a simple, safe, and inexpensive intervention to prevent or delay ESRD in T1D that can be applied at the earliest clinically detectable stages of renal functional decline. It is difficult to overstate how significant this would be, both from the perspective of public health and that of persons with diabetes, adding an estimated 8-10 years free of hemodialysis or kidney transplant to their lives.
摘要 尽管过去20年在血糖和血压(BP)控制方面有所改善,而且引入了 在肾素-血管紧张素系统阻滞剂(RASB)等肾脏保护药物中,终末期肾病的总发生率 1型糖尿病(T1D)的肾病分期(ESRD)没有下降。补充这些的新疗法 迫切需要干预。来自多个队列研究的令人信服的证据表明, 血清尿酸水平(SUA)预测慢性肾脏疾病(CKD)风险的大幅增加 T1D患者肾小球滤过率(GFR)加速丢失。研究血尿酸是否降低 为了减少T1D的GFR损失,我们成立了一个由来自16个学术中心的研究人员组成的独特联盟 在美国、加拿大和丹麦。由共同PI、Joslin Kidney研究的Doria博士和Mauer领导, 该联盟以前是肾素血管紧张素系统研究(RASS)临床试验的PI,现已被命名为 Perl(预防糖尿病早期肾功能丧失)强调相对干预的重点 在T1D的CKD病程早期,肾损害更有可能是可阻止或可逆的, 因此,干预更有可能是有效的。在NIH拨款的支持下R03 DK094484,R34 DK097808、UC4 DK101108和JDRF赠款,Perl财团目前正在进行一项多中心, 双盲临床试验,其中530名T1D患者的≥疗程为8年,轻至中度 肾小球滤过率降低,血尿酸中度升高(≥4.5mgdl),并有尿量升高的病史 白蛋白排泄或肾小球滤过率加速下降随机接受降尿酸药物治疗 别嘌醇(根据肾功能,每天200至400毫克)或安慰剂,为期三年。初级阶段 结果是在2个月的洗脱期结束时的肾小球滤过率(用碘海醇血浆消失率来衡量)。 经过3年的干预。Perl成功地完成了对530名参与者的随机化(多10% 2016年5月),最后一次参与者访问计划于2019年6月进行。Perl 参与者的留存率和忠诚度一直很高。此申请的目的是续订NIH 授予UC4 DK101108,目前支持试验的所有方面,预计将覆盖成本 至2017年10月。该日期之后的资助将允许完成所有Perl的3年治疗期 受试者,这对于有足够的权力回答议定书中描述的审判问题是必要的 由NIDDK和dsmb批准。这笔赠款续期还将为数据分析和 审判结束后的手稿写作。如果Perl证明别嘌醇可以阻止或减缓 在T1D患者中,GFR下降,它将提供一种简单、安全和廉价的干预措施,以防止或 在T1D中延迟ESRD,可在临床上可检测到的肾功能下降的最早阶段应用。它 无论从公共卫生的角度还是从 糖尿病患者,估计使他们的寿命增加8-10年,不进行血液透析或肾移植。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Uric Acid and Diabetic Nephropathy Risk.
  • DOI:
    10.1159/000484284
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mauer M;Doria A
  • 通讯作者:
    Doria A
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Alessandro Doria其他文献

Alessandro Doria的其他文献

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{{ truncateString('Alessandro Doria', 18)}}的其他基金

Early myocardial remodeling and progressive kidney function decline in type 1 diabetes
1 型糖尿病的早期心肌重塑和进行性肾功能下降
  • 批准号:
    10544058
  • 财政年份:
    2021
  • 资助金额:
    $ 25万
  • 项目类别:
A pilot study of fenofibrate to prevent kidney function loss in type 1 diabetes
非诺贝特预防 1 型糖尿病肾功能丧失的初步研究
  • 批准号:
    10471906
  • 财政年份:
    2021
  • 资助金额:
    $ 25万
  • 项目类别:
A pilot study of fenofibrate to prevent kidney function loss in type 1 diabetes
非诺贝特预防 1 型糖尿病肾功能丧失的初步研究
  • 批准号:
    10274529
  • 财政年份:
    2021
  • 资助金额:
    $ 25万
  • 项目类别:
A pilot study of fenofibrate to prevent kidney function loss in type 1 diabetes
非诺贝特预防 1 型糖尿病肾功能丧失的初步研究
  • 批准号:
    10675516
  • 财政年份:
    2021
  • 资助金额:
    $ 25万
  • 项目类别:
Early myocardial remodeling and progressive kidney function decline in type 1 diabetes
1 型糖尿病的早期心肌重塑和进行性肾功能下降
  • 批准号:
    10371705
  • 财政年份:
    2021
  • 资助金额:
    $ 25万
  • 项目类别:
Genotype-dependent cardiovascular and anti-inflammatory effects of fenofibrate
非诺贝特的基因型依赖性心血管和抗炎作用
  • 批准号:
    10223436
  • 财政年份:
    2020
  • 资助金额:
    $ 25万
  • 项目类别:
Genotype-dependent cardiovascular and anti-inflammatory effects of fenofibrate
非诺贝特的基因型依赖性心血管和抗炎作用
  • 批准号:
    10043522
  • 财政年份:
    2020
  • 资助金额:
    $ 25万
  • 项目类别:
PERL: A multicenter clinical trial of allopurinol to prevent GFR loss in T1D
PERL:别嘌呤醇预防 T1D 患者 GFR 损失的多中心临床试验
  • 批准号:
    8644403
  • 财政年份:
    2013
  • 资助金额:
    $ 25万
  • 项目类别:
A multicenter clinical trial of allopurinol to prevent GFR loss in T1D
别嘌呤醇预防 1 型糖尿病 GFR 损失的多中心临床试验
  • 批准号:
    8445008
  • 财政年份:
    2012
  • 资助金额:
    $ 25万
  • 项目类别:
Genetic modifiers of the effect of intensive glycemic control on CVD risk
强化血糖控制对 CVD 风险影响的遗传修饰
  • 批准号:
    8336910
  • 财政年份:
    2011
  • 资助金额:
    $ 25万
  • 项目类别:
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