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Exploring the Mechanisms of Indoxyl Sulfate Production by Oral Tryptophan Challenge Test

NCT04117191 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 42

Last updated 2019-12-10

No results posted yet for this study

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.

Conditions

  • Healthy
  • Chronic Kidney Diseases

Interventions

DIETARY_SUPPLEMENT

Doctor's Best L-Tryptophan

2g tryptophan loading once

Sponsors & Collaborators

  • Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

    lead OTHER

Principal Investigators

  • Ting-Yun Lin, MD. · Taichung Tzu Chi Hospital

Study Design

Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
20 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2019-10-01
Primary Completion
2019-11-30
Completion
2019-11-30

Countries

  • Taiwan

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04117191 on ClinicalTrials.gov