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

NCT04117191 | Completed

• 1 other identifier: 08-P-055
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Chronic Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• Indoxyl sulfate

  serum and urine indoxyl sulfate concentration measurement

  the area under curve of serum and urine indoxyl sulfate within 72 hours

Secondary Outcomes (1)

• Indole-3-acetic acid

  the area under curve of serum and urine Indole-3-acetic acid within 72 hours

Study Arms (1)

Tryptophan loading

EXPERIMENTAL

All participants are introduced to receive tryptophan loading test.

Dietary Supplement: Doctor's Best L-Tryptophan

Interventions

Doctor's Best L-Tryptophan DIETARY_SUPPLEMENT

2g tryptophan loading once

Tryptophan loading

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• (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

Sponsors & Collaborators

• Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation: lead

Study Sites (1)

Taipei Tzu Chi Hospital

New Taipei City, 231, Taiwan

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ting-Yun Lin, MD.

  Taichung Tzu Chi Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Nephrologist

Model Details: All the participants would be introduced to receive 2g tryptophan loading for exploring serum and urine indoxyl sulfate concentration.

Study Record Dates

• First Submitted: September 29, 2019
• First Posted: October 7, 2019
• Study Start: October 1, 2019
• Primary Completion: November 30, 2019
• Study Completion: November 30, 2019
• Last Updated: December 10, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)