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
- 来源:
- 关键词:AdherenceAlberta provinceAlbuminsAllopurinolCanadaChronic Kidney FailureClinicalClinical TrialsCohort StudiesColoradoComplementComplications of Diabetes MellitusConduct Clinical TrialsDataData AnalysesDenmarkDiabetes MellitusDiabetic NephropathyDouble-Blind MethodEarly InterventionEnd stage renal failureExcretory functionFinancial costFundingGlomerular Filtration RateGoalsGrantHemodialysisHumanIncidenceIncreased Uric Acid LevelInsulin-Dependent Diabetes MellitusInterventionIohexolKidneyKidney TransplantationManuscriptsMeasuresMedicineMichiganMinnesotaMorbidity - disease rateMulti-Institutional Clinical TrialNamesNational Institute of Diabetes and Digestive and Kidney DiseasesParticipantPatientsPersonsPharmaceutical PreparationsPlacebosPlasmaPreventionProtocols documentationPublic HealthRandomizedRecording of previous eventsRenal functionRenin-Angiotensin SystemResearch PersonnelResidual stateRiskSerumSiteSocietiesTestingUnited States National Institutes of HealthUniversitiesUrateUric AcidVisitWashingtonWritingblood pressure regulationcollegecostfunctional declinehigh riskloss of functionmortalitynovel therapeuticsoutreachparticipant retentionpreventprimary outcomerecruittreatment durationurinary
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.
总结
尽管在过去的20年里,血压和血压(BP)控制有所改善,
“肾保护”药物,如肾素-血管紧张素系统阻滞剂(RASB),终末-
1型糖尿病(T1 D)中的阶段性肾病(ESRD)并没有下降。新的疗法来补充这些
迫切需要采取干预措施。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)可预测慢性肾脏疾病(CKD)风险的大幅增加,
T1 D患者肾小球滤过率(GFR)下降加快。研究SUA降低是否
可以减少T1 D患者的GFR损失,我们建立了一个由来自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。在共同PI的带领下,来自Joslin肾脏研究的Doria博士和毛尔博士,
原PI的肾素血管紧张素系统研究(RASS)临床试验,该联盟已被命名为
PERL(预防糖尿病早期肾功能丧失)强调其重点是相对干预
在T1 D的CKD病程早期,此时肾损害更可能是不稳定或可逆的,
因此,干预措施更可能有效。在NIH赠款R 03 DK 094484,R34的支持下,
DK 097808,UC 4 DK 101108和JDRF资助,PERL联盟目前正在进行一个多中心,
一项双盲、临床试验,纳入530例病程≥8年的轻度至中度T1 D患者
GFR降低,SUA中度升高(≥4.5 mg/dl),以及尿蛋白升高史
白蛋白排泄或GFR加速下降的患者随机接受降尿酸药物治疗
别嘌呤醇(每天200至400毫克,取决于肾功能)或安慰剂治疗三年。主
结果是2个月洗脱期结束时的GFR(通过碘海醇血浆消失测量)
经过3年的干预。PERL成功地完成了530名参与者的随机化(多出10%)。
2016年5月,最后一次参与者访问计划于2019年6月进行。Perl
参与者的保留和遵守情况非常好。此申请的目的是更新NIH
拨款UC 4 DK 101108,目前支持试验的所有方面,预计将支付费用
直到2017年10月。该日期之后的资金将允许所有PERL完成3年的治疗期
受试者,这是回答方案中描述的试验问题的足够把握度所必需的
经NIDDK和DSMB批准。这项赠款更新还将为数据分析提供支持,
在试验完成后撰写手稿。如果PERL证明别嘌呤醇可以阻止或减缓
在T1 D患者中GFR下降,它将提供一种简单,安全和廉价的干预措施,以预防或
延迟T1 D患者的ESRD,可应用于肾功能下降的最早临床可检测阶段。它
无论从公共卫生的角度还是从社会的角度来看,
糖尿病患者,估计他们的寿命将增加8-10年无需血液透析或肾移植的时间。
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: