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

NCT ID: NCT04117191

Last Updated: 2019-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-01

Study Completion Date

2019-11-30

Brief Summary

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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

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Conditions

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Healthy Chronic Kidney Diseases

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

All the participants would be introduced to receive 2g tryptophan loading for exploring serum and urine indoxyl sulfate concentration.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Tryptophan loading

All participants are introduced to receive tryptophan loading test.

Group Type EXPERIMENTAL

Doctor's Best L-Tryptophan

Intervention Type DIETARY_SUPPLEMENT

2g tryptophan loading once

Interventions

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Doctor's Best L-Tryptophan

2g tryptophan loading once

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* (1) age older than 20 years
* (2) no exposure to antibiotics or probiotics within the 3 months before entering the study.

Exclusion Criteria

* (1) recent gastrointestinal discomfort (such as nausea, vomiting, abdominal pain, constipation, or diarrhea) or
* (2) a history of chronic diseases including diabetes mellites, hypertension, CVD, CKD, liver disease, malignancy, and autoimmune disease.
* (3) pregnancy or breast feeding
* (4) currently use of antipsychotics, Hypnotics, Demerol, Dextromethorphan, tramadol, pentazocine
Minimum Eligible Age

20 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

OTHER

Sponsor Role lead

Responsible Party

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Ting-Yun Lin

Nephrologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ting-Yun Lin, MD.

Role: PRINCIPAL_INVESTIGATOR

Taichung Tzu Chi Hospital

Locations

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Taipei Tzu Chi Hospital

New Taipei City, , Taiwan

Site Status

Countries

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Taiwan

Other Identifiers

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08-P-055

Identifier Type: -

Identifier Source: org_study_id