Ignite Creation Date:
2024-05-06 @ 1:45 PM
Last Modification Date:
2024-10-26 @ 1:19 PM
Study NCT ID:
NCT04117191
Status:
COMPLETED
Last Update Posted:
2019-12-10
First Post:
2019-09-29
Brief Title:
Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test
Sponsor:
Taipei Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation
Organization:
Taipei Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation
Study Overview
Official Title:
Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test
Status:
COMPLETED
Status Verified Date:
2019-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cardiovascular disease CVD is prevalent in patients with chronic kidney disease CKD and is associated with extremely poor prognosis Traditional risk factors for the general population such as diabetes mellitus high blood pressure and dyslipidemia are more common in patients with CKD but cannot fully explain the increased risk of this population New evidence suggests that the uremic milieu itself plays a critical role in the development and progression of CVD The gut microbiota is markedly altered in CKD with overgrowth of bacteria that produce uremic toxins Indoxyl sulfate IS is among the most representative gut-derived uremic toxins and has been most frequently implicated as a contributor to the pathogenesis of CVD in CKD IS is converted from indole a gut bacteria metabolite of dietary tryptophan by two hepatic enzymes CYP2E1 and SULT1A1 The majority of studies have assessed IS toxicity in cultured cells and animal models However human data have been conflicting and the benefit of using orally administered adsorbents to reduce IS levels in unselected CKD patients was not supported by results from the recent randomized controlled trials IS levels may fluctuate widely from time to time with dietary intakes The investigators hypothesize that a postprandial IS concentration may more reflect its toxicity than a single time point fasting or predialysis IS concentration measured in clinical studies Therefore the investigators plan to establish an oral tryptophan challenge test OTCT by using an oral loading of 2 gm tryptophan to simulate the postprandial increase of plasma IS The investigators will recruit 60 healthy volunteers to undergo OTCT A pharmacokinetic study of IS after the OTCT will be performed in 20 of them to verify and simplify the design of OTCT protocol The results of OTCT will be integrated with whole metagenome analysis of fecal microbiota and genetic polymorphism analysis of CYP2E1 and SULT1A1 to explore the mechanisms of IS production In addition to the known genes in microbe produces indoles other supporting bacteria or genes will be examined by using metagenomic shotgun sequencing data
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None