Clinical, Biochemical, and Microbiological Effects of Constipation Treatment in Patients with Chronic Kidney Disease: A Pilot Feasibility Trial
慢性肾病患者便秘治疗的临床、生化和微生物学效果:初步可行性试验
基本信息
- 批准号:10639532
- 负责人:
- 金额:$ 30.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-11 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAlbuminsAnimalsBenignBiochemicalBiologicalCardiovascular systemChronic Kidney FailureClinicalClinical TrialsConstipationDataDefecationDevelopmentDisease ProgressionEconomic BurdenEffectivenessElectrolyte BalanceElectrolytesEquilibriumFiberFluid BalanceFoundationsGastrointestinal DiseasesGoalsHomeostasisHumanInflammatoryInflammatory ResponseIntakeInterventionIntestinal MotilityKidneyLactuloseLiquid substanceMediatingMicrobeModificationOutcomePatientsPerceptionPharmaceutical PreparationsPhenotypePhosphorusPlayPopulationPotassiumProductionQuality of lifeRandomizedResearch DesignResearch Project GrantsRoleSerumSuggestionSymptomsTestingTherapeuticToxinUremiaUrinecomorbidityeffectiveness testingexperimental studyfeasibility testingfeasibility trialgastrointestinalgut microbiotaimprovedlaxativemicrobialmicrobiotanovelopen labelprognosticrandomized trialrecruitsocialtargeted treatment
项目摘要
Constipation is one of the most prevalent gastrointestinal disorders in patients with chronic kidney disease (CKD),
due in part to their multiple comorbidities, concomitant medications, low fiber and fluid intake, and altered gut
microbiota. Although constipation is usually perceived as a benign condition, recent evidence has challenged
this most common perception, demonstrating its independent association with poor clinical outcomes, partly
through the altered gut microbiota favoring the production of fecal metabolites. Among patients with CKD whose
gut plays an important role in the disposal of uremic toxins and in fluid and electrolyte homeostasis, the presence
of constipation can preclude these compensatory mechanisms and may further contribute to their poor clinical
outcomes. Importantly, recent experimental studies in uremic animals have shown that constipation treatment
with laxatives not only accelerated intestinal motility but also modified the gut microbiota and fecal metabolites,
protected the gut barrier, suppressed inflammatory responses, and even ameliorated CKD progression. These
findings led to the suggestion that the adequate management of constipation in patients with CKD may provide
additional therapeutic and prognostic benefits beyond its conventional defecation control. However, no human
studies have yet examined the effects of constipation treatment on clinical outcomes associated with constipation,
or on outcome-related biochemical and microbiological parameters in patients with CKD. The central hypothesis
of this proposal is that treatment of constipation in patients with CKD not only improves their constipation
symptoms but also favorably modifies the relevant biochemical and gut microbial profiles, and ultimately
improves clinical outcomes in these patients. As a first step to test this hypothesis, we propose to perform a
single-center, open-label, randomized, controlled, parallel-group, pilot feasibility trial of a 4-week intervention of
constipation treatment (vs. control) in patients with CKD and constipation, with the following specific aims: 1)
Test the feasibility of delivering the proposed interventions and performing the proposed examinations; and 2)
Determine the effects of constipation treatment on the changes in constipation-related clinical symptoms,
biochemical parameters, and microbial profiles of the gut and circulating microbiota, in a total of 40 patients with
CKD stages G3-G5 and constipation, randomized 1:1 to constipation treatment (with lactulose) vs. control (with
no treatment except bisacodyl rescue therapy). Consistent with the objectives of the small R01 mechanism, this
small, short-term pilot feasibility trial allows us to acquire preliminary data regarding the effects of constipation
treatment on various aspects of patients with CKD and feasibility data related to recruitment, retention, and study
conduct. Furthermore, the findings of this study will lay the foundation for our long-term goal to test the
effectiveness of constipation treatment on several clinical outcomes associated with constipation in CKD in a
large-scale clinical trial, along with the determination of underlying pathophysiological mechanisms, potentially
leading to the development of novel gut-targeted therapeutic strategies to improve clinical outcomes in CKD.
便秘是慢性肾病(CKD)患者中最常见的胃肠道疾病之一,
部分原因是多种合并症、伴随用药、低纤维和液体摄入以及肠道改变
微生物群虽然便秘通常被认为是一种良性疾病,但最近的证据挑战了
这种最常见的看法,证明了其与不良临床结局的独立关联,部分
通过改变肠道微生物群有利于粪便代谢产物的产生。在CKD患者中,
肠道在尿毒症毒素的处置以及体液和电解质的体内平衡中起着重要作用,
便秘可以排除这些代偿机制,并可能进一步导致其不良的临床表现。
成果。重要的是,最近对尿毒症动物的实验研究表明,便秘治疗
泻药不仅加速了肠道运动,而且改变了肠道微生物群和粪便代谢物,
保护肠道屏障,抑制炎症反应,甚至改善CKD进展。这些
研究结果表明,适当的管理慢性肾病患者的便秘,
在常规排便控制之外的额外治疗和预后益处。然而,没有人类
研究已经检验了便秘治疗对与便秘相关的临床结果的影响,
或CKD患者的结局相关生化和微生物学参数。核心假设
这一建议的一个重要方面是,治疗CKD患者的便秘不仅可以改善他们的便秘,
症状,但也有利地改变相关的生化和肠道微生物概况,并最终
改善这些患者的临床结果。作为检验这一假设的第一步,我们建议执行一个
单中心、开放标签、随机、对照、平行组、初步可行性试验,为期4周,
CKD和便秘患者的便秘治疗(与对照组相比),具体目标如下:1)
测试实施拟议干预措施和进行拟议检查的可行性;以及2)
确定便秘治疗对便秘相关临床症状变化的影响,
在总共40名患有糖尿病的患者中,
CKD G3-G5期和便秘,1:1随机分配至便秘治疗组(乳果糖)与对照组(
除比沙可啶补救治疗外,无治疗)。与小R 01机制的目标一致,
一项小型的短期试点可行性试验使我们能够获得有关便秘影响的初步数据
CKD患者各方面的治疗以及与招募、保留和研究相关的可行性数据
行为。此外,这项研究的结果将为我们的长期目标奠定基础,
便秘治疗对慢性肾脏病患者便秘相关临床结局的有效性
大规模临床试验,沿着确定潜在的病理生理机制,
从而导致开发新的肠道靶向治疗策略以改善CKD的临床结局。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Susmita Datta其他文献
Susmita Datta的其他文献
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{{ truncateString('Susmita Datta', 18)}}的其他基金
Increasing the Participation and Visibility of Women in Statistics and Biostatistics
提高妇女在统计和生物统计领域的参与度和知名度
- 批准号:
8652016 - 财政年份:2014
- 资助金额:
$ 30.88万 - 项目类别:
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